Does depression help people do art? Does autism help people do science? Does the normal mind without enough of either come up short in creativity? Not sure. But relatives of those with depression have different intellectual interests than relatives of those who have autism.
A hallmark of the individual is the cultivation of personal interests, but for some people, their intellectual pursuits might actually be genetically predetermined. Survey results published by Princeton University researchers in the journal PLoS ONE suggest that a family history of psychiatric conditions such as autism and depression could influence the subjects a person finds engaging.
Although preliminary, the findings provide a new look at the oft-studied link between psychiatric conditions and aptitude in the arts or sciences. While previous studies have explored this link by focusing on highly creative individuals or a person's occupation, the Princeton research indicates that the influence of familial neuropsychiatric traits on personal interests is apparently independent of a person's talent or career path, and could help form a person's basic preferences and personality.
Princeton researchers surveyed nearly 1,100 students from the University's Class of 2014 early in their freshman year to learn which major they would choose based on their intellectual interests. The students were then asked to indicate the incidence of mood disorders, substance abuse or autism spectrum disorder (ASD) in their family, including parents, siblings and grandparents.
Students interested in pursuing a major in the humanities or social sciences were twice as likely to report that a family member had a mood disorder or a problem with substance abuse. Students with an interest in science and technical majors, on the other hand, were three times more likely to report a sibling with an ASD, a range of developmental disorders that includes autism and Asperger syndrome.
I suspect moderate doses of genes for autism make the mind much more capable of handling the rigor required to do math and science. The "normal" human mind is not as well suited to understand the world scientifically.
What I wonder: does maladaptive autism exist further out on a spectrum from adaptive autistic traits? Or is maladaptive autism caused by other genetic variants beyond those that cause more adaptive forms of altruism?
Here's the abstract and full paper.
From personality to neuropsychiatric disorders, individual differences in brain function are known to have a strong heritable component. Here we report that between close relatives, a variety of neuropsychiatric disorders covary strongly with intellectual interests. We surveyed an entire class of high-functioning young adults at an elite university for prospective major, familial incidence of neuropsychiatric disorders, and demographic and attitudinal questions. Students aspiring to technical majors (science/mathematics/engineering) were more likely than other students to report a sibling with an autism spectrum disorder (p = 0.037). Conversely, students interested in the humanities were more likely to report a family member with major depressive disorder (p = 8.8×10−4), bipolar disorder (p = 0.027), or substance abuse problems (p = 1.9×10−6). A combined PREdisposition for Subject MattEr (PRESUME) score based on these disorders was strongly predictive of subject matter interests (p = 9.6×10−8). Our results suggest that shared genetic (and perhaps environmental) factors may both predispose for heritable neuropsychiatric disorders and influence the development of intellectual interests.
Since genetic sequencing costs have crashed over the the last decade and especially in the last few years we are about to get the flood of DNA sequencing data needed to identify large numbers of genetic variants that contribute to cognitive traits. The picture will be much much clearer in just 4 or 5 years. I'm awaiting the discoveries with great interest.
Does someone choose to be understanding and sympathetic? Or do genetic variants for an oxytocin receptor in the brain make people more or less empathetic in very easily recognizable ways? Read below and guess which variants of the oxytocin receptor gene you carry.
CORVALLIS, Ore. – Scientists have discovered that a gene that influences empathy, parental sensitivity and sociability is so powerful that even strangers observing 20 seconds of silent video identified people with a particular genetic variation to be more caring and trusting.
In the study, 23 romantic couples were videotaped while one of the partners described a time of suffering in their lives. The other half of the couple and their physical, non-verbal reactions were the focal point of the study. Groups of complete strangers viewed the videos. The observers were asked to rate the person on traits such as how kind, trustworthy, and caring they thought the person was, based on just 20 seconds of silent video.
"Our findings suggest even slight genetic variation may have tangible impact on people's behavior, and that these behavioral differences are quickly noticed by others," said Aleksandr Kogan, a postdoctoral fellow at the University of Toronto and the study's lead author.
The study builds on previous research conducted by Sarina Rodrigues Saturn, an assistant professor of psychology at Oregon State University. In that study, Saturn and her colleagues linked a genetic variation that affects hormone/neurotransmitter oxytocin's receptor to empathy and stress reactivity. Saturn is senior author on the new study, which is in the latest issue of Proceedings of the National Academy of Sciences (PNAS).
The standard question I always wonder when I read reports about genes causing cognitive differences: Which genetic variants will people choose for their offspring when they become able to make such choices? Will the world become a more or less empathetic place once people can choose which genes their kids can get? Will humanity diverge into very empathetic and very not empathetic groups? Will the empathetic empathize even with the turbo unempathetic?
Perhaps the GGs and AAs should form their own social media social circles.
"It was amazing to see how the data aligned so strongly by genotype," Saturn said. "It makes sense that a gene crucial for social processing would yield these findings; other studies have shown that people are good at judging people at a distance and first impressions really make an impact."
Before the videos were recorded, the scientists tested the couples and identified their genotype as GG, AG, or AA. Individuals homozygous for the G allele (carrying two copies of the G version of the gene) of the oxytocin receptor tend to be more "prosocial," defined by researchers as the ability to behave in a way that benefits another person. In contrast, the carriers of the A version of the gene (AG or AA genotypes) tend to have a higher risk of autism, as well as self-reported lower levels of positive emotions, empathy and parental sensitivity.
The carriers of the AA variants are least trusted.
Oxytocin has already been significantly linked with social affiliation and reduction in stress. It is a peptide made in the hypothalamus and has targets all over the body and the brain. It is best known for its role in female reproduction and is associated with social recognition, pair bonding, dampening negative emotional responses, trust and love.
Out of the 10 people who were marked by the neutral observer as "most prosocial, six carried the GG genotype associated with the oxytocin receptor; of the 10 people who were marked as "least trusted," nine were carriers of the A version of the gene. The people carrying an A version of the gene were viewed as less kind, trustworthy and caring toward their partners in the video.
Possibly the neutral observers are also responding to genetic variants of other genes that tested for in this study.
Imagine you are hiring nurses. Do you want AA or GG nurses? I'm thinking GG since patients want to feel their nurses care about their well-being. On the other hand, kindness is probably a risk factor for a prison guard and probably isn't a desirable trait in a loan officer either.
Maybe some day you won't friend someone on Facebook without first checking for genetic compatibility. A paper published in PNAS finds that dopamine receptor gene DRD2 seems to cause people to befriend those who also have the same genetic variant whereas with another gene called CYP2A6 the opposite seems to be the case.
With one gene, called DRD2, which has been associated with alcoholism, they found clusters of friends with the very same marker.
Another gene called CYP2A6, which has a suspected role in the metabolism of foreign bodies including nicotine, appeared more divisive. People with this gene seemed to steer clear of those who also carry the gene.
DRD2's previous known association with alcoholism might give a clue to this result. Maybe social drinkers are more likely to form friendships with other social drinkers.
People who had a genetic variant of a gene associated with an open personality, CYAP26, tended to have friends who did not share this genetic variant.
A replication study in an independent sample from the Framingham Heart Study verifies that DRD2 exhibits significant homophily and that CYP2A6 exhibits significant heterophily. These unique results show that homophily and heterophily obtain on a genetic (indeed, an allelic) level, which has implications for the study of population genetics and social behavior. In particular, the results suggest that association tests should include friends’ genes and that theories of evolution should take into account the fact that humans might, in some sense, be metagenomic with respect to the humans around them.
I see a way to use this line of research: You know how it is that parents do not want their kids associating with the wrong types? Well, in the future prospective parents will be able to choose genetic variants that will assure that many years later Johnnie or Jill won't want to associate with troublemakers and apprentice criminals in high school. Just give your babies genes that make them feel aversion to bad influences.
Do you like to do good things for other people? If so, your genes might be responsible for this. At least, the results of a study conducted by researchers of the University of Bonn suggest this. According to the study, a minute change in a particular gene is associated with a significantly higher willingness to donate. People with this change gave twice as much money on average to a charitable cause as did other study subjects. The results have now been published in the journal Social Cognitive & Affective Neuroscience (doi: 10.1093/scan/nsq083).
The researchers working with the psychologist Professor Dr. Martin Reuter invited their students to take a "retention test": The roughly 100 participants were to memorize series of numbers and then repeat them as correctly as possible. They received the sum of five Euros for doing this. Afterwards, they could either take their hard-earned money home or donate any portion of it to a charitable cause. This decision was made freely and in apparent anonymity. "However, we always knew how much money was in the cash box beforehand and could therefore calculate the amount donated", explains Reuter.
COMT-Met carriers do not give up as much money.
This mini-mutation also has effects on behavior: "Students with the COMT-Val gene donated twice as much money on average as did fellow students with the COMT-Met variant", explains Reuter. This is the first time that researchers have been able to establish a connection between a particular gene and altruistic deeds. However, it was already known from studies on twins that altruistic behavior is also partly influenced by our genes.
This seems fairly easily testable on larger populations. This reminds me: We need web sites where people to use genetic testing services such as 23andme can submit their genetic testing results and take a lot of online tests to check various hypotheses and theories about genes and human nature. A study like the one above could be tested with many thousands of volunteers.
These results point out why we should have the legally recognized right (tell the FDA) to do direct-to-consumer genetic testing btw: If people are free to get lots of genetic test data collected on them on their own nickel then massive voluntary studies of genes and human nature and health could be conducted without anyone ever showing up at a medical clinic or research facility. This could lower the cost of genetic research on humanity by orders of magnitude.
Sensation seeking has been linked to a range of behavior disorders, such as drug addiction. It isn't all bad, though. "Not everyone who's high on sensation seeking becomes a drug addict. They may become an Army Ranger or an artist. It's all in how you channel it," says Jaime Derringer, a PhD student at the University of Minnesota and the first author of the study. She wanted to use a new technique to find out more about the genetics of sensation seeking. Most obvious connections with genes, like the BRCA gene that increases the risk for breast cancer, have already been found, Derringer says. Now new methods are letting scientists look for more subtle associations between genes and all kinds of traits, including behavior and personality.
Derringer used a kind of mutation in DNA called a single-nucleotide polymorphism, or SNP. A SNP is a change in just one "letter" of the DNA.
Note that single letter differences are just one of a few genetic differences possible. But SNPs are cheaper to test for. So they get more research attention.
She started by picking eight genes with various roles related to the neurotransmitter dopamine, which has been linked to sensation seeking in other studies. She looked at group of 635 people who were part of a study on addiction. For each one, she had genetic information on 273 SNPs known to appear in those 8 genes and a score for how much they were inclined to sensation seeking. Using that data, she was able to narrow down the 273 SNPs to 12 potentially important ones. When she combined these 12 SNPs, they explained just under 4 percent of the difference between people in sensation seeking. This may not seem like a lot, but it's "quite large for a genetic study," Derringer says.
Note that the 12 genes suspected of having influence might only explain 4% of the variation in sensation seeking. The emerging picture with genetic variants that influence cognitive processes is that each variant makes only a small contribution. The same has been found in the search for genetic variants that influence intelligence. This highlights the need for very large populations of study subjects in order to discover the signal of very small genetic influences.
In this study the researchers used only used genetic material 635 people. Not enough to discover hundreds of genetic variants that each might contribute a fraction of one percent to the total tendency toward sensation seeking. What's needed are full genetic sequences of hundreds of thousands of people. But that would cost orders of magnitude more to do. Fortunately the cost of genetic testing and genetic sequencing continues to fall by orders of magnitude. So the flood of data needed to tease out of the contributing genetic variants is going to come in the next 5 years. We'll see bigger data sets and larger number of genetic influences identified each year.
"We examine a wide range of consumer judgment and decision-making phenomenon and discover that many—though not all of them—are in fact heritable or influenced by genetic factors," write authors Itamar Simonson (Stanford University) and Aner Sela (University of Florida, Gainesville).
The authors studied twins' consumer preferences to determine whether or not certain behaviors or traits have a genetic basis. "A greater similarity in behavior or trait between identical than between fraternal twins indicates that the behavior or trait is likely to be heritable," the authors explain.
The preference for a sure gain versus a gamble has a substantial genetic component. Not surprising. Utilitarian versus self-indulgent choices also not surprisingly have a genetic influence. Some specific products including chocolate have a genetic influence. It is good to know I have a genetic bond with fellow science fiction lovers. Hello brothers and sisters. Isn't Blade Runner great?
The authors discovered that people seem to inherit the following tendencies: to choose a compromise option and avoid extremes; select sure gains over gambles; prefer an easy but non-rewarding task over an enjoyable challenging one; look for the best option available; and prefer utilitarian, clearly needed options (like batteries) over more indulgent ones (gourmet chocolate). They also found that likings for specific products seemed to be genetically related: chocolate, mustard, hybrid cars, science fiction movies, and jazz.
A liking for tattoos does not appear to be heritable. But I'm hoping that an aversion to tattoos could some day be genetically engineered into offspring using a new genetic variation.
The researchers also found that some tendencies did not seem to be heritable—for example, a preference for a smaller versus larger product variety or likings for ketchup and tattoos.
Children whose mothers are genetically predisposed to have impaired production of serotonin appear more likely to develop attention-deficit hyperactivity disorder (ADHD) later in life, according to a report in the October issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Would tryptophan or serotonin supplementation cut the risk of developing ADHD as a child?
Anne Halmøy, M.D., of University of Bergen, Norway, and colleagues studied 459 adult outpatients with ADHD, 97 of their family members and 187 control individuals recruited from across Norway. Participants provided blood samples for gene sequencing along with information about psychiatric diagnoses and symptoms.
By sequencing 646 individuals, the researchers identified nine different mutations, of which eight were significantly associated with impaired function of the enzymes. Family analysis of 38 individuals who carried these mutations and 41 of their offspring revealed that children of mothers who had one of the mutations—and, therefore, had impaired serotonin production—had a 1.5- to 2.5-time higher risk of ADHD than control individuals or offspring of fathers with the mutations.
I think we are getting close to the age when most genetic factors that contribute to cognitive performance become known. This makes the advantages from in vitro fertilization combined with genetic testing. The advantage from starting pregnancies will become so compelling that a rising fraction of all pregnancies will be started with IVF.
In children inattention leads to depression but hyperactivity ups the risk of suicide. Makes sense in a way: hyperactive people have the energy to kill themselves.
The authors also categorized ADHD into three subtypes and found that each one (inattentiveness, hyperactivity and/or a combination of the two) predicted somewhat different outcomes. While children who have a combination of inattention and hyperactivity predicted both depression and attempted suicide, children who experience only inattentiveness predicted only depression. Children showing only hyperactivity predicted suicide attempts but not depression.
With the exception of X and Y chromosome genes in men, we have copies of each gene from both parents. Researchers find that in mice (and likely in humans as well) specific genes from one or the other parent are silenced so that only one parent contributes to resulting phenotype (visible appearances and functionality).
The new findings, reported in two papers that appear in the early online edition of the journal Science on July 8, 2010, suggest that imprinting has a significant influence on brain development and behavior. It also likely contributes to diseases of the brain, since imprinting occasionally shuts down the only good gene in a pair.
Howard Hughes Medical Institute investigator Catherine Dulac led the team of scientists who conducted the ambitious analysis. Christopher Gregg, a postdoctoral fellow in her Harvard University lab, is the lead author on both of the publications.
“Essentially what we found with these two studies is that imprinting is not only very extensive but also seems to be subject to a lot of regulation, throughout the life of an individual and even according to brain region and gender,” says Dulac. “And that makes the phenomenon absolutely fascinating.”
This result helps explain why genetic causes of disease, IQ, physical appearances, and other qualities are so hard to track down. The simple Mendelian model of inheritance works in some cases. But for the genes identified in this study the Mendelian model doesn't predict what happens.
Whether the gene from mother or father gets expressed depends on the specific gene, whether the offspring is female or male, and even on stage of development.
Another striking finding was that paternal and maternal imprinting isn’t evenly mixed: About 60 percent of the imprinted genes in the mouse embryonic brain turned out to be maternal, while about 70 percent of the imprinted genes in the adult brain are paternal. Thus, in early life, it appears that imprinting mostly reflects the mother’s influence, and later gives way to the father’s. “But the majority of the genes that we found are imprinted during development, which is when mothers have the greatest influence,” says Dulac.
In their second paper, Dulac and her team reported that the gene imprinting in an animal can vary depending on whether the animal is male or female. Throughout the genome, they found 347 genes that appeared to be imprinted in adult female mice but not males, or vice versa. This sex-specific imprinting was particularly evident in females in the hypothalamic region of the brain, which mediates maternal and mating behaviors. One example of the complexity they encountered is the gene Mrpl48, which they found has a paternal expression bias in the hypothalamus of females, but not males.
Geneticists need to identify for about 20,000 human genes whether their maternal or paternal version is always active or suppressed in each tissue type at each stage of development and do this for men and women and across races.
Microsoft co-founder Paul Allen has spent royally on research to chart which genes are active in each part of the human brain. One result is the Allen Human Brain Atlas. If you want to journey into the the world of brain's gene expression here's your chance.
SEATTLE, Wash.—May 24, 2010—The Allen Institute for Brain Science announced today that it has launched the Allen Human Brain Atlas, a publicly available online atlas charting genes at work throughout the human brain. The data provided in this initial data release represent the most extensive and detailed body of information about gene activity in the human brain to date, documenting which genes are expressed, or "turned on" where. In the coming years, the Atlas will be expanded with more data and more sophisticated search, analysis and visualization tools to create a comprehensive resource useful to an increasingly wide range of scientists and research programs worldwide.
The Allen Human Brain Atlas, available at www.brain-map.org, is a unique multi-modal atlas of the human brain that integrates anatomic and genomic information to create a searchable, three-dimensional map of gene activity in the brain. Data modalities in this resource include magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and histology—providing information about gross neuroanatomy, pathways of neural connections, and microscopic anatomy, respectively—as well as gene expression data derived from multiple approaches.
June 3, 2010- A Johns Hopkins and Japanese research team has generated the first comprehensive genetic “parts” list of a mouse hypothalamus, an enigmatic region of the brain — roughly cherry-sized, in humans — that controls hunger, thirst, fatigue, body temperature, wake-sleep cycles and links the central nervous system to control of hormone levels.
Flaws in hypothalamus development may underlie both inborn and acquired metabolic balance problems that can lead to obesity, diabetes, mood disorders and high blood pressure, according to a report on the study published May 2 in the advance online publication ofNature Neuroscience.
Gene microarrays were used to measure gene expression of very small and thin slices of mouse brains.
The team’s first challenge was to dissect away, at the very start of neural development, the part of the mouse brain which develops into the hypothalamus, and then cut tiny slices of this region for use in microarray analysis, a technology that reveals multiple gene activity. By analyzing all the roughly 20,000 genes in the mouse genome, the team identified 1200 as strongly activated in developing hypothalamus and characterized the cells within the hypothalamus in which they were activated. The team then characterized the expression of the most interesting 350 genes in detail using another gene called Shh, for sonic hedgehog, as a landmark to identify the precise region of the hypothalamus in which these genes were turned on. This involved processing close to 20,000 tissue sections — painstakingly sliced at one-fiftieth of a millimeter thickness and then individually examined.
20 years ago research that looked at the genetic activity of so many genes simultaneously was not practical. Now the ability to look at gene activity of hundreds or thousands of genes at the same time makes possible a much more detailed look at how the brain functions. The tools for doing this are of such recent vintage that the full effects of the existence of these tools has yet to be felt. In the 2010s the amount of data collected about gene expression will go up by orders of magnitude and the meaning of brain genes will become much clearer.
Feb. 10, 2010 -- Researchers with the National Institutes of Health (NIH) have identified three genes that may predispose people to stuttering -- a condition that affects 3 million Americans and 5% of young children.
Because stuttering tends to run in families, it has long been suspected that genes play a role in the speech disorder.
The GNPTAB, GNPTG, and NAGPA variants were found in only a small proportion of cases, together accounting for 21 of 393 cases in unrelated, affected subjects — a finding that is consistent with the genetic heterogeneity that underlies stuttering.8,9,10,11 Causative factors in the remaining 95% of cases remain to be elucidated. Because the identified variants are rare, they would have escaped detection on a standard genomewide association screen.
Massive cheap genetic scanning is needed to tease out the many genetic causes of stuttering. The same is true for many other genetically caused disorders. Fortunately genetic testing and sequencing has fallen by orders of magnitude in recent years and the cost declines continue. That's why we are seeing more reports of discoveries of causes of genetically caused disorders. I predict we will soon see a lot of reports about genetic causes of personality and IQ differences because the tools are finally available to collect sufficient amounts of genetic data to discover the causes.
GNPTAB encodes its enzyme with the help of another gene called GNPTG. In addition, a second enzyme, called NAGPA, acts at the next step in this process. Together, these enzymes make up the signaling mechanism that cells use to steer a variety of enzymes to the lysosome to do their work. Because of the close relationship among the three genes in this process, the GNPTG and NAGPA genes were the next logical place for the researchers to look for possible mutations in people who stutter. Indeed, when they examined these two genes, they found mutations in individuals who stutter, but not in control groups.
The GNPTAB and GNPTG genes have already been tied to two serious metabolic diseases known as mucolipidosis (ML) II and III. MLII and MLIII are part of a group of diseases called lysosomal storage disorders because improperly recycled cell components accumulate in the lysosome. Large deposits of these substances ultimately cause joint, skeletal system, heart, liver, and other health problems as well as developmental problems in the brain. They are also known to cause problems with speech.
“You might ask, why don’t people with the stuttering mutations have more serious complications? Why don’t they have an ML disease?” posed Dr. Drayna, senior author of the paper. “ML disorders are recessive. You need to have two copies of a defective gene in order to get the disease. Nearly all of the unrelated individuals in our study who stuttered had only one copy of the mutation. Also, with stuttering, the protein is still made, but it’s not made exactly right. With ML diseases, the proteins typically aren’t made at all. Still, there are a few complexities remaining to be understood, and we’d like to learn more about them.”
Some researchers at Hebrew U, National University of Hong Kong, and Hong Kong U have taken a look at whether a gene for breaking down neurotransmitters (e.g. serotonin, norepinephrine, epinephrine, and dopamine) influences risk taking behavior. If you like to gamble rather than buy insurance you can blame it on your monoamine oxidase A gene (MAOA) high activity allele.
Decision making often entails longshot risks involving a small chance of receiving a substantial outcome. People tend to be risk preferring (averse) when facing longshot risks involving significant gains (losses). This differentiation towards longshot risks underpins the markets for lottery as well as for insurance. Both lottery and insurance have emerged since ancient times and continue to play a useful role in the modern economy. In this study, we observe subjects' incentivized choices in a controlled laboratory setting, and investigate their association with a widely studied, promoter-region repeat functional polymorphism in monoamine oxidase A gene (MAOA). We find that subjects with the high activity (4-repeat) allele are characterized by a preference for the longshot lottery and also less insurance purchasing than subjects with the low activity (3-repeat) allele. This is the first result to link attitude towards longshot risks to a specific gene. It complements recent findings on the neurobiological basis of economic risk taking.
Regular readers will anticipate this question: When it becomes possible to select genes for offspring will people prefer genes for risk taking? Or the genes for playing it safe and buying insurance? You can imagine that the insurance industry and gambling industry will promote conflicting choices of genes for future generations. Which industry will win?
The discussion section of this paper (which is on Plos One and therefore open access) references research into other genes that influence risk taking. One can imagine that someone with enough different risk taking alleles either ruins their life gambling or they take up dangerous sports.
Several recent papers have explored the molecular genetic basis of economic risk taking. With 95 subjects, Dreber et al.  showed that the dopamine receptor D4 gene (DRD4) exon 3 repeats are associated with financial risk taking. This was replicated independently in a 65-subject study by Kuhnen & Chiao  who found additionally an association with the serotonin transporter (5-HTTLPR). Zhong et al.  proposed a neurochemical model relating dopamine and serotonin tones respectively to valuation sensitivity over gains and losses and derived its implication on risk attitude over risks involving moderate probabilities. They tested and validated their hypothesis with a gene association experiment showing that dopamine transporter (DAT1) is associated with risk attitude over gains and that an intronic 17 bp variable number of tandem repeat of serotonin transporter (STin2) is associated with risk attitude over losses. Roe et al.  showed that economic risk attitude is associated with several vesicular monoamine transporter (VMAT2) SNPs. The present paper is the first investigation of the neurogenetic correlates of attitude towards longshot risks observed through laboratory-based economic experiments. Our findings complement existing evidence about the role of MAOA in the modulation of personality traits including harm avoidance .
If I was going to select a genetic profile for an offspring with all the knowledge we'll have 10 years from now I'd be tempted to select the genes that make the ultimate rational trader. I figure a lot of wealthy people will do just that and the effect will be to increase inequality as genetically wealthy people out-compete others in making investment decisions.
Writing in The Economist Geoffrey Miller says in 2010 human genetic research results will show some politically incorrect beliefs about human nature are correct. Looking ahead to 2010 and beyond I am reminded of Dr. Elisabeth Kubler-Ross's 5 stages of death. I think these apply to beliefs as well.
Human geneticists have reached a private crisis of conscience, and it will become public knowledge in 2010. The crisis has depressing health implications and alarming political ones. In a nutshell: the new genetics will reveal much less than hoped about how to cure disease, and much more than feared about human evolution and inequality, including genetic differences between classes, ethnicities and races.
Miller says the political earth-shaking data has been collected and is in the publication pipeline for Nature Genetics and other leading research publications. This is a case where the future is happening faster than I expected. I've been writing posts filed under my Biotech Advance Rates chronicling the rapid decline in costs for genetic testing and DNA sequencing. The price drops have been in the orders of magnitude and were even faster than I was optimistically hoping for. With the cost of full genome sequencing below $10k and headed soon below $1k the amount of DNA sequencing data has turned into a flood. Hence the resulting flood of research papers.
DNA chips have enabled cheap comparison of lots of people for DNA sequence variations associated with physical and behavioral (e.g. criminal, personality types, behavioral problems) traits.
About five years ago, genetics researchers became excited about new methods for “genome-wide association studies” (GWAS). We already knew from twin, family and adoption studies that all human traits are heritable: genetic differences explain much of the variation between individuals. We knew the genes were there; we just had to find them. Companies such as Illumina and Affymetrix produced DNA chips that allowed researchers to test up to 1m genetic variants for their statistical association with specific traits. America’s National Institutes of Health and Britain’s Wellcome Trust gave huge research grants for gene-hunting. Thousands of researchers jumped on the GWAS bandwagon. Lab groups formed and international research consortia congealed. The quantity of published GWAS research has soared.
The DNA chips can only test for known variations and it is my impression (someone correct me if I'm wrong) that the DNA chips can only check for single letter differences - not large copy variations. But the plunging costs for full genome sequencing will enable pretty much all genetic differences to be compared and we can expect even bigger discoveries in 2011, 2012, and out years.
A lot of people are going to be upset by the truth about human nature and for a number of reasons. Certainly people who want others to think of all humans as equal aren't going to like seeing tons of details about our innate inequality reaching the mainstream. Also, the discovery of a long list of genetic differences that cause behavioral differences will reduce the extent to which we can think of ourselves as possessing free will. Implications for criminal justice arise. If some guy can be shown to be innately criminal then why let him free in civilization?
I expect cheap genetic testing to change mating practices in many ways. For example, someone who wants a faithful spouse could surreptitiously test a potential mate for genes that contribute to marital infidelity. The gene AVPR1a also influences altruism and monogamy. Mates might also be selected based on genes that influence trust-related behavior.
I expect online dating services will compare genetic profiles to allow people to find mates who have desired genes. I expect online dating services to start doing genetic comparisons by 2015 if not sooner. I also expect more women will opt to use sperm donors once they are in a position to compare the genetic profiles of guys who are willing to raise kids with them to the best genetic profiles for sperm bank donors. Already more single women are using sperm donors. Detailed information about the benefits and downsides of each man's DNA will heighten competition and, as a result, evolution will accelerate.
Parenthetically, Miller is an evolutionary psychologist at the University of New Mexico and author of some useful and insightful books about human nature. I am currently reading his book Spent: Sex, Evolution, and Consumer Behavior and can highly recommend it. The book will make you more aware of your own instinctive desires for higher status and help you restrain your desires to buy things to demonstrate higher status. As Miller reports, research into status signals finds that guys who buy Rolexes, fancy cars, and other status symbols overestimate the status-boosting effects these goods will have on others. My advice: Spend less on status symbols and save your money to spend on the first rejuvenation therapies. They aren't coming as soon as the genetic truth about human nature. But rejuvenation therapies are coming.
Update: What I want to know: Will Leftists once again embrace eugenics? Or perhaps will both the Left and Right split into new rival camps over selective breeding of future generations of humans? New moral issues (at least new to the larger public) can reveal differences within existing factions.
I expect eugenic breeding practices to widen the differences between nations and cultures as different groupings make different decisions on average about offspring genetic endowments. If for some reason we are not replaced by robots or nanobots I expect the human race to splinter into new and not entirely compatible species.
CORVALLIS, Ore. – Researchers have discovered a genetic variation that may contribute to how empathetic a human is, and how that person reacts to stress. In the first study of its kind, a variation in the hormone/neurotransmitter oxytocin's receptor was linked to a person's ability to infer the mental state of others.
Interestingly, this same genetic variation also related to stress reactivity. These findings could have a significant impact in adding to the body of knowledge about the importance of oxytocin, and its link to conditions such as autism and unhealthy levels of stress.
Does the ability to read others cut or increase stress? I can see it cutting both ways. Sometimes obliviousness would be an advantage if everyone around you was anxious or depressed. Picking up on their signals would tend to bring you down. On the other hand, sometimes it is dangerous not to be able to read the emotional signals of others.
Can you read the minds of others?
One of the tests used to measure empathy included the "Reading the Mind in Eyes" test, created by Simon Baron-Cohen (cousin of actor/comedian Sacha Baron Cohen). Rodrigues said that this test is commonly used to discern how individuals can put themselves into the mind of another person, which overlaps with empathy, because it tests how well the participant can infer someone's emotional state by their eyes.
"In general, women do better on this test than men," Rodrigues said. "But we found a stark difference in both sexes based on the genetic variation." Those with the GG genetic variation were 22.7 percent less likely to make a mistake on the "Reading the Mind in the Eyes" test than the other individuals.
The article mentions a previous research report that found oxytocin spray given to autistics boosted the scores on behavioral and dispositional empathy measures. I'd like to know whether everyone would get a boost of greater social competence from a snort of oxytocin.
A variety of mental states have utility in different forms. Sometimes you just need to be a calculator. Sometimes you need to be a logic chopper. Other times you need to be a able to read people like a bunch of open books. It'd be helpful to be able to shift around into different useful mental states depending on the circumstances.
30% of the American public carry a gene that probably makes them more dangerous on the road. Hey, these people ought to move to cities and take mass transit.
Bad drivers may in part have their genes to blame, suggests a new study by UC Irvine neuroscientists.
People with a particular gene variant performed more than 20 percent worse on a driving test than people without it - and a follow-up test a few days later yielded similar results. About 30 percent of Americans have the variant.
"These people make more errors from the get-go, and they forget more of what they learned after time away," said Dr. Steven Cramer, neurology associate professor and senior author of the study published recently in the journal Cerebral Cortex.
We are not all as well adapted genetically to industrialized civilization. This one gene, brain-derived neurotrophic factor (BDNF), is just one of many genes where we differ from each other in our ability to handle the many products and environmental niches we've created with industrialization. Some people can't handle beer or cocaine or addictive drugs. Some other people can't handle the sleep deprivation made easier by Thomas Edison's invention of the light bulb. Still others can't handle easy access to online gambling or online porn.
Not enough BDNF means your brain functions less well behind the wheel.
This gene variant limits the availability of a protein called brain-derived neurotrophic factor during activity. BDNF keeps memory strong by supporting communication among brain cells and keeping them functioning optimally. When a person is engaged in a particular task, BDNF is secreted in the brain area connected with that activity to help the body respond.
I wonder whether 29 people can provide enough data points to demonstrate an effect. But if the effect is strong maybe it can.
The driving test was taken by 29 people - 22 without the gene variant and seven with it. They were asked to drive 15 laps on a simulator that required them to learn the nuances of a track programmed to have difficult curves and turns. Researchers recorded how well they stayed on the course over time. Four days later, the test was repeated.
Results showed that people with the variant did worse on both tests than the other participants, and they remembered less the second time. "Behavior derives from dozens and dozens of neurophysiologic events, so it's somewhat surprising this exercise bore fruit," Cramer said.
In the future will some people look at their brain gene test results and decide to live next to a subway stop?
Update: If this discovery holds up under further investigation it will be unusual. In the search for genes that influence cognitive ability the researchers are finding that it is hard to find the genetic variants which contribute to differences. They know the variants are there from twins studies and other studies on populations. The thinking now is that bulk of the variants which influence cognitive ability each have only a small influence. So much larger populations are needed to find them.
Researcher Robert Plomin comments that so far the genetic differences influencing IQ appear to each contribute very little to the total differences.
Failing to find genes for intelligence has, in itself, been very instructive for Plomin. Twin studies continue to persuade him that the genes exist. “There is ultimately DNA variation responsible for it,” he says. But each of the variations detected so far only makes a tiny contribution to differences in intelligence. “I think nobody thought that the biggest effects would account for less than 1 percent,” Plomin points out.
That means that there must be hundreds--perhaps thousands--of genes that together produce the full range of gene-based variation in intelligence.
Check out this brief essay by Plomin about IQ and genes in Technology Review.
An article in New Scientist takes a look at recent neuroscience research on learning. Among the topics covered: The COMT gene which is involved in dopamine metabolism has a version that improves the ability to pay attention.
Education before school can have benefits further down the track, Posner says. The neurotransmitter dopamine has been shown to play an important role in the function of the anterior cingulate gyrus, and genetic variations in the dopamine system seem to interact with parenting quality to affect executive function. Posner found that children between 18 and 21 months old with a particularly active variant of the COMT gene, which leads to less dopamine transmission, showed improved attention compared with those carrying other variants. The children also responded especially well to high-quality parenting (Neuroscience, DOI: 10.1016/j.neuroscience.2009.05.059).
The article discusses how individual genetic profiles could lead to personalized methods to optimize learning. In my view the use of such genetically guided teaching strategies will increase differences in educational outcome. Look at the COMT variant mentioned above. Kids who have it will benefit more from high-quality parenting. Okay, so kids identified from genetic testing as having greater capacity to pay attention will get taught stuff faster and more intensely because they'll be recognized as more able to stay focused and absorb information from longer stretches of learning. They'll rise above their peers that much faster.
Advances in methods of teaching will, on average, amplify the effects of differences in abilities. Only gene therapies, cell therapies, and other methods for changing brain metabolism can enable the cognitively less well endowed close some of the gap with the cognitively most able.
June 26, 2009 - (BRONX, NY) - A variation in a gene that is active in the central nervous system is associated with increased risk for obesity, according to an international study in which Albert Einstein College of Medicine of Yeshiva University played a major role. The research adds to evidence that genes influence appetite and that the brain plays a key role in obesity.
Robert Kaplan, Ph.D., associate professor of epidemiology & population health, helped direct the international study, which involved 34 research institutions and is published online in PLoS Genetics. Dr. Kaplan and his U.S. and European colleagues found that people who have inherited the gene variant NRXN3 have a 10-15 percent increased risk of being obese compared with people who do not have the variant.
The researchers examined data from eight studies involving genes and body weight. These studies included more than 31,000 people of European origin, ages 45 to 76, representing a broad range of dietary habits and health behaviors.
After analyzing more than two million regions of the human genome, the researchers found that the NRXN3 gene variant ─ previously associated with alcohol dependence, cocaine addiction, and illegal substance abuse ─ also predicts the tendency to become obese. Altogether, researchers found the gene variant in 20 percent of the people studied.
NRXN3 has also been implicated in addiction.
Since NRXN3 is active in the brain and also implicated in addiction, these traits may share some neurologic underpinnings.
Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.
Another paper from the same issue of Plos Genetics finds still more genes that influence obesity and fat distribution.
Here, we describe a meta-analysis of genome-wide association data from 38,580 individuals, followed by large-scale replication (in up to 70,689 individuals) designed to uncover variants influencing anthropometric measures of central obesity and fat distribution, namely waist circumference (WC) and waist–hip ratio (WHR). This work complements parallel efforts that have been successful in defining variants impacting overall adiposity and focuses on the visceral fat accumulation which has particularly strong relationships to metabolic and cardiovascular disease. Our analyses have identified two loci (TFAP2B and MSRA) associated with WC, and a further locus, near LYPLAL1, which shows gender-specific relationships with WHR (all to levels of genome-wide significance). These loci vary in the strength of their associations with overall adiposity, and LYPLAL1 in particular appears to have a specific effect on patterns of fat distribution. All in all, these three loci provide novel insights into human physiology and the development of obesity.
Expect to see a continued acceleration of the rate of gene searches looking for genetic variants that cause behavioral and health differences. Genetic sequencing and genetic testing costs have fallen so fast that the full effect of the price drops hasn't filtered through to published papers. The price drops continue because the technology continues to advance rapidly. So the amount of data available for gene searches keeps going up faster. This flood of data is going to lead to a flood of findings. The most dramatic consequence will be a big acceleration in human evolution.
Do you mentally function well when sleep-deprived? I personally make more spelling mistakes when writing blog posts after midnite. Given the right variant of the gene PER3 the human mind becomes more active in response to reduced sleeping.
New imaging research in the June 24 issue of The Journal of Neuroscience helps explain why sleep deprivation affects some people more than others. After staying awake all night, those who are genetically vulnerable to sleep loss showed reduced brain activity, while those who are genetically resilient showed expanded brain activity, the study found. The findings help explain individual differences in the ability to compensate for lack of sleep.
"The extent to which individuals are affected by sleep deprivation varies, with some crashing out and others holding up well after a night without sleep," said Michael Chee, MBBS, at the Duke–National University of Singapore Graduate Medical School, an expert on sleep deprivation who was not affiliated with the study. However, studying how the brain produces these behavioral differences is difficult: researchers usually do not know whether their study participants will be vulnerable to sleep deprivation until after a study is complete. Previous studies have shown conflicting results, perhaps because the study subjects differed widely in vulnerability to sleep deprivation.
In the current study, the researchers, led by Pierre Maquet, MD, at the University of Lìege in Belgium and Derk-Jan Dijk, PhD, at the University of Surrey in the United Kingdom, avoided this problem by selecting study participants based on their genes. Previous research showed that the PERIOD3 (PER3) gene predicts how people will respond to sleep deprivation. People carry either long or short variants of the gene. Those with the short PER3 variant are resilient to sleep loss — they perform well on cognitive tasks after sleep deprivation. However, those with the long PER3 variant are vulnerable — they show deficits in cognitive performance after sleep deprivation. Now the new study explains why.
Do the people with the short PER3 variant get any advantages over those with the long variant when they are well rested? It could be that lowered cognitive performance when tired also reduces harm to the brain when it is not well rested. Some of the genes that provide advantages in some environments also come at a cost in the same or other environments.
In the first study, published in the journal Cognition & Emotion (Vol.23: No.4), Pizarro and co-authors Yoel Inbar of Harvard University's Kennedy School of Government and Paul Bloom of Yale University surveyed 181 U.S. adults from politically mixed "swing states." They subjected these adults to two indexes: the Disgust Sensitivity Scale (DSS), which offers various scenarios to assess disgust sensitivity, and a political ideology scale. From this they found a correlation between being more easily disgusted and political conservatism.
To test whether disgust sensitivity is linked to specific conservative attitudes, the researchers then surveyed 91 Cornell undergraduates with the DSS, as well as with questions about their positions on issues including gay marriage, abortion, gun control, labor unions, tax cuts and affirmative action.
Participants who rated higher in disgust sensitivity were more likely to oppose gay marriage and abortion, issues that are related to notions of morality or purity. The researchers also found a weak correlation between disgust sensitivity and support for tax cuts, but no link between disgust sensitivity and the other issues.
I expect scientists will continue to discover more connections between genetically caused and congenital characteristics of the brain on the one hand, and political leanings, moral beliefs, and social behaviors on the other. Ditto for economic behaviors such as one's willingness to save for the future or gamble.
These discoveries about innate causes of beliefs and behavior will have opposing effects on political debate. On the one hand some might introspect and decide not to put as much stock in their feelings about what is right. Why believe something just because you were born with a propensity to believe it? On the other hand, a lot of people will think their political beliefs are rational and sensible but the opposing side is obviously wrong due to that opposing side being born mentally defect and prone to being wrong and even evil.
Take the study above for example. I can hear some liberals thinking "See, this shows that conservatives are wrong on gay marriage because they have irrational reactions to the thought of it". Evidence of a behavior's inherited cause can easily be seen as evidence that some group is defective. If you just do not happen to have the same genetic leanings as they do then you are genetically blessed with the ability to see the world accurately - unlike the hell spawn on the opposing side.
Another study released back in July 2008 found genes influence the odds one will vote or engage in political activities.
The decision to vote is partly genetic, according to a new study published in the American Political Science Review. The research, by James H. Fowler and Christopher T. Dawes, of the University of California, San Diego and Laura A. Baker, of the University of Southern California, is the first to show that genes influence participation in elections and in a wide range of political activities. See the full study here.
Fowler and Dawes have followed this work with research just published in the July issue of the Journal of Politics in which they identify a link between two specific genes and political participation. They show that individuals with a variant of the MAOA gene are significantly more likely to have voted in the 2000 presidential election. Their research also demonstrates a connection between a variant of the 5HTT gene and voter turnout, which is moderated by religious attendance. These are the first results ever to link specific genes to political behavior. The published study will be online July 1, but a pre-publication PDF is linked here.
MADISON — The ability to empathize with others is partially determined by genes, according to new research on mice from the University of Wisconsin-Madison and Oregon Health and Science University (OHSU).
In the study, a highly social strain of mice learned to associate a sound played in a specific cage with something negative simply by hearing a mouse in that cage respond with squeaks of distress. A genetically different mouse strain with fewer social tendencies did not learn any connection between the cues and the other mouse's distress, showing that the ability to identify and act on another's emotions may have a genetic basis. The new research will publish Wednesday, Feb. 11, in the Public Library of Science ONE journal at http://dx.plos.org/10.1371/journal.pone.0004387.
Like humans, mice can automatically sense and respond to others' positive and negative emotions, such as excitement, fear or anger. Understanding empathy in mice may lead to important discoveries about the social interaction deficits seen in many human psychosocial disorders, including autism, schizophrenia, depression and addiction, the researchers say. For example, nonverbal social cues are frequently used to identify early signs of autism in very young children.
"The core of empathy is being able to have an emotional experience and share that experience with another," says UW-Madison graduate student Jules Panksepp, who led the work along with undergraduate QiLiang Chen. "We are basically trying to deconstruct empathy into smaller functional units that make it more accessible to biological research."
Here comes a question that is predictable for long time readers (at least those with the right genetic complement): Will people choose to make their genetically engineered offspring more or less empathetic than the average human is now?
People with the short serotonin transporter gene, 5-HTTLPR (two copies of the short allele), relative to those with the long version of that polymorphism (at least one copy of the long allele), invested 28 percent less in a risky investment. Similarly, people who carry the 7-repeat allele of the DRD4 gene in the dopamine family, relative to those carrying other versions of that gene, invested about 25 percent more in a risky investment.
"Our research pinpoints, for the first time, the roles that specific variants of the serotonin transporter gene and the dopamine receptor gene, play in predicting whether people are more or less likely to take financial risks," said Camelia M. Kuhnen, assistant professor of finance, Kellogg School of Management at Northwestern. "It shows that individual variability in our genetic makeup effects economic behavior."
"Genetic Determinants of Financial Risk Taking will be published online Wednesday, Feb. 11, by the open-access journal PLoS ONE. The study's co-investigators are Kuhnen and Joan Y. Chiao, assistant professor of psychology at Northwestern.
Prior research linking the two genetic variants of 5-HTTLPR and DRD4 to, respectively, negative emotion and addiction behaviors suggested to the Northwestern researchers that those particular brain mechanisms could play a role in financial risk-taking. But until the Northwestern study, the identification of specific genes underlying financial-risk preferences remained elusive.
When people gain the ability to choose genes for their offspring will they opt for a shorter or longer version of this gene? How will future humans differ from present humans genetically?
I picture Jack Nicholson saying "you can't handle the truth" and Tom Cruise says "I got the genetic profile that says I can". Of course, maybe he doesn't. Post-traumatic stress disorder (PTSD) has a big genetic component for vulnerability to it after a great shock.
Earthquakes have aftershocks — not just the geological kind but the mental kind as well. Just like veterans of war, earthquake survivors can experience post-traumatic stress disorder, depression and anxiety.
In 1988, a massive earthquake in Armenia killed 17,000 people and destroyed nearly half the town of Gumri. Now, in the first multigenerational study of its kind, UCLA researchers studying survivors of that catastrophe have discovered that vulnerability to PTSD, anxiety and depression runs in families.
Armen Goenjian, a research psychiatrist in the UCLA Department of Psychiatry and Biobehavioral Sciences, and colleagues studied 200 participants from 12 multigenerational families exposed to the earthquake. Participants suffered from varying degrees of the disorders. The researchers found that 41 percent of the variation of PTSD symptoms was due to genetic factors and that 61 percent of the variation of depressive symptoms and 66 percent of anxiety symptoms were attributable to genetics. Further, they found that a large proportion of the genetic liabilities for the disorders were shared.
The research appears in the December issue of the journal Psychiatric Genetics.
These genetic factors that contribute to PTSD will eventually be identified. I see this as a problematic turn of events for police departments, fire departments, militaries, and other organizations that put people in dangerous situations. People whose genetic profiles show they will get messed up permanently from getting into firefights are better off not getting into combat. Of course, combat poses other threats like getting one's leg or arm blown off that are going leave you seriously messed up or dead regardless of your genetic inheritance. But the total average cost of going into combat will be higher for people who have a genetic predisposition to get PTSD.
On the bright side, a discovery of which genes contribute to PTSD risk will help in the development of drugs that will prevent PTSD. That'll work better for combat troops than for people who get into natural disasters since the combat troops can start taking the protective drugs before they go into battle. Whereas many types of disasters like tornadoes and volcanic eruptions can come on too quickly for people to start using drugs in advance to prevent mental changes that'll permanently scar them.
EAST LANSING, Mich. — A groundbreaking study of popularity by a Michigan State University scientist has found that genes elicit not only specific behaviors but also the social consequences of those behaviors.
According to the investigation by behavioral geneticist S. Alexandra Burt, male college students who had a gene associated with rule-breaking behavior were rated most popular by a group of previously unacquainted peers.
The devil made me do it by giving me a serotonin gene variant.
Burt collected DNA from more than 200 male college students in two separate samples. After interacting in a lab setting for about an hour, the students filled out a questionnaire about whom they most liked in their group. In both samples, the most popular students turned out to be the ones with a particular form of a serotonin gene that was also associated with rule-breaking behavior.
“So the gene predisposed them to rule-breaking behavior and their rule-breaking behavior made them more popular,” Burt said.
Break the rules to become more popular. Blame your genes if you get caught.
6 genetic variants variants have been identified as possible contributing factors for obesity. 5 of them are expressed in the brain.
A genetic study of more than 90,000 people has identified six new genetic variants that are associated with increased Body Mass Index (BMI), the most commonly used measure of obesity. Five of the genes are known to be active in the brain, suggesting that many genetic variants implicated in obesity might affect behaviour, rather than the chemical processes of energy or fat metabolism.
Obesity is an increasing problem that results in individual risk to health as well as increasing burdens on health care systems. By identifying genetic variants that affect obesity, researchers hope to understand better the mechanisms regulating energy balance, which will guide the development of new therapies and help to develop improved diagnosis.
These genes reduce the human capacity to exercise free will. People who want to lose weight but find themselves compelled to eat do not have free will over the amount of food they consume.
For example, one of the genes, NEGR1, controls how your brain is wired as it is developing by regulating neuronal growth, Abecasis said.
"In younger children, ages 5-10, we found that with three of (the genes) the children were already heavier at that young age, and with the other three genes, we saw that there was no effect on children," he said. "For those, we only saw an effect in much older individuals. This points to different mechanisms influencing your weight at different ages."
Another example is SH2B1, which was first discovered by U-M researchers studying mice, Abecasis said. Researchers created an obese mouse then returned it to its normal weight by turning on the SH2B1 gene in the brain.
We are going to hear about many more genetic variants that influence behavior every year. The cost of genetic testing has dropped so far that studies search through large amounts of genetic data are becoming cheaper and more feasible to do. Costs of genetic testing and genetic sequencing will continue to plummet and the rate of discovery will continue to rise.
Are you easily startled? When DNA testing becomes very cheap you'll be able to find out if your COMT gene is to blame. If you can't stop from fixating on bad memories and fixate on bad scary things happening around you blame it on your COMT gene.
Inborn differences may help explain why trauma gives some people bad memories and others the nightmare of post-traumatic stress. Scientists in Germany and the United States have reported evidence linking genes to anxious behavior.
Researchers including Martin Reuter, PhD, of the University of Bonn, Germany, recruited 96 women averaging 22 years old from the Giessen Gene Brain Behavior Project, which investigates biomolecular causes of individual differences in behavior.
The researchers first determined which participants carried which variations (alleles) of the COMT gene, which encodes an enzyme that breaks down dopamine, weakening its signal. (COMT stands for a catabolic enzyme named catechol-O-methyltransferase.) Scientists call its two alleles Val158 and Met158. Depending on ethnicity, more or less half the population carries one copy of each. The rest of the population is roughly divided between carrying two copies of Val158 and two copies of Met158.
Using a well-validated psychophysiological measure, the researchers next measured the intensity of each participant's startle response by attaching electrodes to the eye muscles that, upon emotional arousal, contract and cause a blink. Participants then viewed pictures that were emotionally pleasant (such as animals or babies), neutral (such as a power outlet or hairdryer), or aversive (such as weapons or injured victims at a crime scene) -- 12 pictures of each type for six seconds each. A loud, 35-millisecond white noise, called a startle probe, sounded at random while they watched. When participants blinked, showing the startle response, a bioamplifier took readings from the electrodes and sent the information to a computer for analysis.
People carrying two copies of the Met158 allele of the COMT gene showed a significantly stronger startle reflex in the unpleasant-picture condition than did carriers of either two copies of Val158 allele or one copy of each. The two-Met carriers also disclosed greater anxiety on a standard personality test.
This finding confirms that specific variations in the gene that regulates dopamine signaling may play a role in negative emotionality. The authors speculated that the Met158 allele may raise levels of circulating dopamine in the brain's limbic system, a set of structures that support (among other things) memory, emotional arousal and attention. The researchers said that more dopamine in the prefrontal cortex could result in an "inflexible attentional focus" on unpleasant stimuli, meaning that Met158 carriers can't tear themselves away from something that's arousing -- even if it's bad.
Unpleasant stimuli are often undesirable conditions in one's environment. One can imagine why the tendency to focus on such things would be adaptive. Some of them would be problems that needed solving or threats that needed combating.
COMT is probably one of many genes that influence anxiety and the startle reflex. For some reason the Met158 allele of COMT is fairly new in human evolution. I wonder what the selective pressures were that led to its emergence.
The Met158 allele was created by a relatively recent mutation and only in the evolution of human beings. Other primate species such as chimpanzees carry only the Val/Val genotype. Co-author Christian Montag, Dipl. Psych., observes that for humans, wariness may have been adaptive. He points out, "It was an advantage to be more anxious in a dangerous environment."
Genetic variations in a protein that causes blood vessel growth, vascular endothelial growth factor (VEGF), appears to cause differences in brain size.
New Haven, Conn. — The size of a key area of the brain involved in memory and mood disorders is influenced by variation in a growth factor gene that influences blood vessel growth and has been widely studied in heart disease and cancer, Yale University researchers have found.
The magnetic resonance imaging brain scanning and genetics study, published online Tuesday in the journal Biological Psychiatry, is another piece of emerging evidence suggesting that vascular endothelial growth factor, or VEGF, may be crucial to mental health. And the variations in brain volume associated with the VEGF gene suggest a possible cause of cognitive symptoms reported by some patients using anti-VEGF therapies for cancer and other diseases.
We are on the cusp of a period of great discoveries in brain genetics. Hundreds (or perhaps thousands) of genetic variations that influence personality, behavior, and intellectual abilities will be discovered in the next decade. One use of this information will be to select between embryos for implantation when doing in vitro fertilization (IVF). In fact, the ability to use the genetic discoveries to select embryos will drive a surge in the use of IVF as people try to give their kids every possible competitive advantage.
Some of the genetic discoveries will be usable by those of us who already exist. For example, it will probably become possible to use gene therapy and cell therapy to change which genetic version of VEGF a person has as a way to boost blood vessel growth in the hippocampus. This might improve memory formation and reduce depression.
Now it appears that this growth factor may also be crucial for the development and repair of the hippocampus, an area of the brain where memory is consolidated and which has been implicated in mood disorders such as depression and in dementias such as Alzheimer’s disease.
Here's another report on our role as puppets with genes as the puppeteers. A group of researchers has published a paper in Nature Genetics offering evidence that genes involved in calcium ion flow across nerve membranes might contribute to bipolar depression.
The largest genetic analysis of its kind to date for bipolar disorder has implicated machinery involved in the balance of sodium and calcium in brain cells. Researchers supported in part by the National Institute of Mental Health, part of the National Institutes of Health, found an association between the disorder and variation in two genes that make components of channels that manage the flow of the elements into and out of cells, including neurons.
"A neuron's excitability – whether it will fire – hinges on this delicate equilibrium," explained Pamela Sklar, M.D., Ph.D., of Massachusetts General Hospital (MGH) and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, who led the research. "Finding statistically robust associations linked to two proteins that may be involved in regulating such ion channels – and that are also thought to be targets of drugs used to clinically to treat bipolar disorder – is astonishing."
People with bipolar disorder have my sympathy. Until researchers can come up with better treatments for it a lot of people have to go thru a lot of suffering. Nature is a sadistic bastard.
Since researchers think many genes contribute to bipolar it is hard to pick out the genes that contribute from all the background noise. But the genes they suspect are involved in key functions done by neurons and the researchers had a large sample of bipolar and non-bipolar study participants for which they did DNA tests.
To boost their odds, Sklar and colleagues pooled data from the latter two previously published and one new study of their own. They also added additional samples from the STEP-BD study and Scottish and Irish families, and controls from the NIMH Genetics Repository. After examining about 1.8 million sites of genetic variation in 10,596 people – including 4,387 with bipolar disorder – the researchers found the two genes showing the strongest association among 14 disorder-associated chromosomal regions.
Variation in a gene called Ankyrin 3 (ANK3) showed the strongest association with bipolar disorder. The ANK3 protein is strategically located in the first part of neuronal extensions called axons and is part of the cellular machinery that decides whether a neuron will fire. Co-authors of the paper had shown last year in mouse brain that lithium, the most common medication for preventing bipolar disorder episodes, reduces expression of ANK3.
Variation in a calcium channel gene found in the brain showed the second strongest association with bipolar disorder. This CACNA1C protein similarly regulates the influx and outflow of calcium and is the site of interaction for a hypertension medication that has also been used in the treatment of bipolar disorder.
The fact that a hypertension medication works against bipolar is interesting though not unprecedented. Lots of drugs are originally developed for one reason and found to have benefits for other disorders.
Note that they looked at 1.8 million sites of known genetic variation. Ongoing projects aimed at identifying all sites where we genetically differ make this sort of study possible where it wouldn't have been possible even 5 years ago. Faster and cheaper ways to do DNA testing are going to cause a massive torrent of brain gene discoveries over the next 5 years.
In 2001, Breiter collaborated with Daniel Kahneman, PhD, of Princeton University and Peter Shizgal, PhD, Concordia University, Montreal, to show how the brain's reward/aversion circuitry followed the principles of what is called prospect theory when responding to the anticipation and receipt of a financial reward, helping to lay the groundwork for the field now called neuroeconomics. Kahnemann was a co-recipient of the 2002 Nobel Prize in economics for his earlier development of prospect theory, which describes the different ways people evaluate positive and negative outcomes in uncertain situations.
The current report connects molecular genetics with earlier studies of choice and preference and with investigations of the brain's reward circuitry. The researchers focused on a gene called CREB1 that has been implicated in animal studies of the brain's reward/aversion function. Study lead author Roy Perlis, MD, medical director of the MGH Bipolar Program, and colleagues previously found that depressed men with a particular variation near the gene coding for CREB report greater difficulty suppressing anger. Another study of theirs associated the same variation with a threefold greater risk of suicidal thinking in major depressive disorder patients soon after beginning antidepressant therapy. The 28 participants in the current study had no evidence of any psychiatric disorder or physical disorder that might influence brain activity.
Willingness to view expressions of different emotions seems influenced by which version of CREB1 you have.
In addition to analyzing each participant's version of the CREB1 gene, the researchers conducted a set of experiments. As the participants viewed facial expressions reflecting different emotional states – happy, neutral, sad, fearful and angry – fMRI scans were taken to examine the activity of brain structures associated with processing pleasant or unpleasant experiences. In another test, participants viewed the same pictures and could change how long they viewed an image by the way they pressed keys on a keyboard. Many earlier studies have established the keypress experiment as a quantitative measure of preference. In the version used in this study, keypress responses reflected participants' judgment and decisions about how much or how little they preferred the facial expressions.
The fMRI study showed that, during the viewing of angry faces, the activity of a structure called the insula, involved in the response to unpleasant situations, depended on which version of the CREB1 gene a participant inherited. In the keypress experiment, responses indicating a preference against the angry expression paralleled the CREB1-affected fMRI activity seen in the insula in the first experiment and also differed depending on the CREB1 variant that had been inherited.
This one gene accounts for 20% of the differences seen in how people chose options in response to the facial expressions.
"We were surprised to see that variation in the CREB1 gene would account for more than 20 percent of the difference in how healthy participants weighed different options and expressed specific preferences," says Perlis. "Our previous studies and the work of other groups suggested that variation in this gene could be important for judgment and decision-making by the brain, but we needed to connect this to a measurable decision-making effect in both behavior and brain activity."
If more genes exist which influence how people react then future discoveries will leave even less room for free will. This process of discovery will repeat for more genes and more aspects of human behavior. These researchers are already looking into other genes which might influence thought and behavior.
Breiter adds, "This study connects quantitative measurements across three levels of observation – brain activity, genomic variation and the expression of preference. We now are investigating the potential role of other genes and will go on to assess how this relationship across three levels of observation may be affected by conditions such as depression and addiction."
Update: The more our personalities are found to be determined by genes the more human nature will change once selection of genes for offspring (basically offspring genetic engineering) becomes possible. People are bound to make some decisions for offspring genes that are different than what the offspring would get naturally. If people become empowered to make decisions that change a large variety of cognitive characteristics then they will make those decisions. What decisions will they make? That is one of the biggest questions we face about the future of humanity.
If you could get into a time machine and pop out 100 years in the future would you find the personalities you meet congenial? Enjoyable to be around? Cut-throat? Amoral? Extremely pushy and aggressive? Will something resembling civil society still exist? Will humans live in enormous tension with each other? The genetic variations exist to make all these outcomes possible. Which outcomes occur (and the answer may differ by country, religion, social class, etc) will be determined by the genetic choices people make for their offspring.
Before spending a lot of money on piano and singing lessons some day parents will be able to get their kids genetically tested to check for musically inclined genetic profiles. Why waste all that money on a kid who might turn out to be innately tone deaf? A fairly preliminary study in Finland finds evidence for a genetic component to musical ability.
Molecular and statistical genetic studies in 15 Finnish families have shown that there is a substantial genetic component in musical aptitude. Musical aptitude was determined using three tests: a test for auditory structuring ability (Karma Music test), and the Seashore pitch and time discrimination subtests. The study represents the first systematic molecular genetic study that aims in the identification of candidate genes associated with musical aptitude.
The identified regions contain genes affecting cell extension and migration during neural development. Interestingly, an overlapping region previously associated with genetic locus for dyslexia was found raising a question about common evolutionary background of music and language faculties. The results show that musical aptitude is likely to be regulated by several predisposing genes/variants.
“The identification of genes/genetic variants involved in mediating music perception and performance would offer new tools to understand the role of music in human brain function, human evolution and its relationship to language faculty”, says the leader of the study, Dr. Irma Järvelä from the University of Helsinki.
While this study did not identify specific genetic variants as causes of differences in musical ability that level of detail will not be a long time in coming. The continued rapid decline in genetic sequencing costs will make complete personal genetic sequencing affordable in the 2010s. The resulting flood of genetic sequencing data will make identification of genetic causes of cognitive abilities far easier to do than is the case today.
By the year 2035 I expect enhanced musical ability to become a very popular option for parents making genetic engineering decisions in the design of their children.
Some forms of a gene that controls the body's response to stress hormones appear to protect adults who were abused in childhood from depression, psychiatrists have found.
People who had been abused as children and who carried the most protective forms of the gene, called corticotropin-releasing hormone receptor one (CRHR1), had markedly lower measures of depression, compared with people with less protective forms, the researchers found in a recent study.
The findings could guide doctors in finding new ways to treat depression in people who were abused as children, says senior author Kerry Ressler, MD, PhD, assistant professor of psychiatry and behavioral sciences at Emory University School of Medicine.
This is not the first report of genetic variations of brain genes that affect how well developing children handle abuse and adversity. Previous research found that children who carry the low MAOA activity allele (MAOA-L) and who are abused demonstrate more aggressive and violent behavior as adults.
Some kids have genes that let them shrug off all sorts of abuse and basically keep trucking. Other kids aren't so lucky. Those latter kids become problems for the rest of us too. Violence prone adults pose a danger to whoever they come into contact with.
Early identification of kids with genetic vulnerabilities might some day get used to guide more aggressive state intervention into bad families. You can imagine social workers arguing to take a kid out of an abusive home more quickly if the has genes that make him or her vulnerable to permanent and problematic behavioral and personality alterations.
Once offspring genetic engineering becomes possible we can't assume parents should avoid giving offspring these genetic variations that make kids more vulnerable to abuse. There might be benefits to these alleles in more benign environments. Though I see a more compelling argument for discouraging the passing along of these alleles if either prospective parent has a genetic profile and brain scans that suggests he or she is likely to abuse kids.
Here is news some new moms can use. Whether breast feeding will boost offspring IQ comes down to which genetic variations the babies carry.
DURHAM, N.C. – The known association between breast feeding and slightly higher IQ in children has been shown to relate to a particular gene in the babies, according to a report this week in the Proceedings of the National Academy of Sciences.
In two studies of breast-fed infants involving more than 3,000 children in Britain and New Zealand, breastfeeding was found to raise intelligence an average of nearly 7 IQ points if the children had a particular version of a gene called FADS2.
The distribution of FADS2 genetic variants probably varies around the world. Anyone know of a source of data for FADS2 genetic variant distributions in human races and local ethnic groups? That information would probably indicate whether results would hold up in all human populations.
"There has been some criticism of earlier studies about breastfeeding and IQ that they didn't control for socioeconomic status, or the mother's IQ or other factors, but our findings take an end-run around those arguments by showing the physiological mechanism that accounts for the difference," said Terrie Moffitt, a professor of psychological and brain sciences in Duke University's Institute for Genome Sciences and Policy.
Moffitt, who performed the research with her husband and co-author Avshalom Caspi at King's College in London, found that the baby's intellectual development is influenced by both genes and environment or, more specifically, by the interaction of its genes with its environment.
"The argument about intelligence has been about nature versus nurture for at least a century," Moffitt said. "We're finding that nature and nurture work together."
These results suggest that most women should breast feed. Only 10% of the women in the study groups had babies with genetic profiles which prevented a benefit from breast feeding.
Ninety percent of the children in the two study groups had at least one copy of the "C" version of FADS2, which yielded higher IQ if they were breast-fed. The other 10 percent, with only the "G" versions of the gene, showed no IQ advantage or disadvantage from breastfeeding.
A cheap test for FADS2 variants could help millions of women weigh the costs and benefits of breast feeding. Find out from a genetic test whether newly born junior will turn out smarter if you structure your life so that breast feeding is practical.
The benefit of the "C" version of FADS2 might come from its ability to convert other fatty acids to DHA.
The gene was singled out for the researchers' attention because it produces an enzyme that helps convert dietary fatty acids into the polyunsaturated fatty acids DHA (docosahexaenoic acid) and AA (arachidonic acid) that have been shown to accumulate in the human brain during the first months after birth.
A baby formula high in DHA might deliver the same benefit as breast feeding and deliver that benefit regardless of genetic variations carried by a baby. Mom eating salmon every day and then breast feeding might similarly deliver that benefit regardless of genetic variation.
A 7 point IQ boost is a really big deal. A country that boosted its average IQ by 7 points would experience a huge boost in economic growth and a rise in per capita GDP as the smarter kids made their way into the labor market.
The variation of apolipoprotein E known as apoE4 gene doesn't just increase the risk of Alzheimer's Disease. Carriers of the apoE4 genetic variant show differences in mental performance as children.
PORTLAND, Ore. - Children who possess a gene known to increase the risk of Alzheimer's disease already show signs of reduced cognitive function, an Oregon Health & Science University study has found.
Scientists in the OHSU School of Medicine discovered that 7- to 10-year-olds with a member of a family of genes implicated in development, nerve cell regeneration and neuroprotection display reduced spatial learning and memory, associated with later-life cognitive impairments.
Results of the study, presented today at Neuroscience 2007, the 37th annual meeting of the Society for Neuroscience in San Diego, suggest that changes predisposing a person to Alzheimer's and other forms of dementia might occur much sooner in the brain than previously thought.
"One of our questions has been is this a risk that only happens with age, or is it already - early on - the cause of differences in performance," said study co-author Jacob Raber, Ph.D., associate professor of behavioral neuroscience and neurology in the OHSU School of Medicine. "This study suggests there already are cognitive differences very early on in life."
The researchers looked at 55 kids aged 7 to 10.
"When we looked at non-demented healthy elderly, we saw the clear effect of apoE4," he said. "So it's not just Alzheimer's disease. ApoE4 carriers generally do worse in our tests. Among the nondemented oldest old, where the mean age is 82, those who have apoE4 do less well" on cognitive tests.
In their study on children, Raber and colleagues - lead author Summer Acevedo, Ph.D., OHSU postdoctoral fellow, and Byung Park, Ph.D., senior biostatistics associate in the OHSU Biostatistics & Bioinformatics Shared Resource - examined 55 healthy boys and girls ages 7 to 10. Among them were eight girls and six boys who carried the apoE4 gene, and 17 girls and 24 boys who didn't.
Quite a few leftists want us to accept as a matter of secular faith that genetic variants don't create substantial differences in intellectual performance. But the accumulating evidence unsurprisingly (after all, the mind is a manifestation of physical phenomena) says otherwise.
Falling costs and falling risks for starting pregnancies in vitro are probably going to lead many prospective parents to select against embryos that carry apoE4. What ambitious parent wants their son or daughter to do poorly on the "Memory Island" test? None I hope.
Raber, Acevedo and Park found that apoE4 carriers scored lower in location recognition tests, and non-apoE4 carriers outperformed apoE4 carriers in the "Memory Island" test by navigating closer to the visible target location. Also, non-apoE4 carriers showed spatial memory retention when a target wasn't present and searched more frequently for the targets in the appropriate quadrants while apoE4 carriers did not.In all, 75.6 percent non-apoE4 carriers showed target preference compared with only 43 percent of apoE4 carriers.
I'd like to know the frequency of apoE4 as a function of social class, level of education, tested IQ, and income. Does apoE4 show up at lower frequency in smarter people?
I'd also like to know what advantage apoE4 confers that allowed it to become fairly frequent in human populations. One source on apoE4 frequencies in different populations puts it at 11.7% in Tyrolean Europeans, 37% in Khoi San blacks, and 4.9% in Chinese. In recent centuries has apoE4 experienced selective pressure against it?
There's been controversy on whether those who take selective serotonin reuptake inhibitor (SSRI) antidepressants are at greater risk of thinking suicidal thoughts. It is a difficult effect to tease out since people depressed enough to take SSRIs are already at greater risk of depression and some of them probably become less at risk of suicide because SSRIs brighten their mood. But maybe others react to SSRIs by becoming more suicidal. Well, genetic testing might have allowed some scientists to discover who will be at greater risk of suicidal thoughts as a result of taking an SSRI. People taking the SSRI drug citalopram who have certain variants of glutamate receptor genes are at much higher risk of suicide thoughts.
Specific variations in two genes are linked to suicidal thinking that sometimes occurs in people taking the most commonly prescribed class of antidepressants, according to a large study led by scientists at the National Institutes of Health’s (NIH) National Institute of Mental Health (NIMH). Depending on the particular mix inherited, these versions increased the likelihood of such thoughts from 2- to15-fold, the study found. About 1 percent of adult patients were deemed to be at high genetic risk, 41 percent at elevated risk and 58 percent at lower risk.
If confirmed, the findings may hold promise for genetic testing, as more such markers are identified.
The "If confirmed" is important. They looked at many genes and so a false positive just by chance is possible.
Risk increased proportionately if a participant had two, as opposed to just one of the suspect versions. Both genes code for components of the brain’s glutamate chemical messenger system, which recent studies suggest is involved in the antidepressant response.
Overall, about 6 percent of 1,915 patients with depression reported that they started to have suicidal thoughts while taking an antidepressant. This rate soared to 36 percent among the few patients with both of the suspect gene versions; 59 percent of the patients who had suicidal thoughts had at least one of the versions.
Francis J. McMahon, M.D., Gonzalo Laje, M.D., NIMH Mood and Anxiety Disorders Program, and colleagues at the National Human Genome Research Institute (NHGRI), Mount Sinai School of Medicine, and the University of Texas Southwestern Medical Center, report on their findings in the October, 2007 issue of The American Journal of Psychiatry.
We are well within 10 years of widespread use of genetic testing when choosing between drugs and making other treatment decisions. Clinical practice will take a big turn when genetic tests can predict which drugs will cause which side effects in each patient.
The researchers found that certain versions of two genes that code for glutamate receptors – the receiving stations for the neurotransmitter’s chemical messages – were more prevalent in patients with suicidal thinking. How the newly identified versions affect the workings of glutamate receptors to confer increased risk remains to be discovered. It’s also not yet known whether the findings generalize to other antidepressants.
One percent of the study participants had a version of the kainate receptor gene, GRIK2, that increased the odds for suicidal thinking more than 8-fold. Forty-one percent of participants had a version of the AMPA receptor gene, GRIA3, that raised the odds nearly 2-fold. About one-half of 1 percent of participants had both high risk gene versions, boosting the odds 15 fold – but this was the case for only 11 participants, of whom four developed suicidal thinking.
The size of the observed effects makes it likely that their finding is real. It is the sort of result that could be confirmed pretty quickly with sufficient funding.
A discovery like this one is not just useful for making drug choices. It also provides clues about what causes people to become suicidal. A better understanding of the mechanisms which cause suicidal thoughts will lead to ways to stop suicidal thoughts.
Philadelphia, PA, September 26, 2007 – Do gene variants that convey risk for schizophrenia affect apparently healthy individuals" Although these genes are present in every human, individuals may have different versions of these genes, called alleles. While many people who possess these “risk alleles” do not end up with schizophrenia, this does not mean they are unaffected by the presence of the risk allele. In the largest study of its kind to date, scheduled for publication in the October 1st issue of Biological Psychiatry, researchers sought to examine the impact of a few particular genes, known to be associated with a diagnosis of schizophrenia, on a healthy population.
Stefanis and colleagues recruited more than 2000 young men and measured dimensions of their cognitive abilities that tend to be impaired in individuals diagnosed with schizophrenia. The authors also measured schizotypal personality traits, which represent behaviors that are associated with schizophrenia, such as atypical behaviors and beliefs, suspiciousness or paranoia, and discomfort in social situations. They then genotyped these volunteers in relation to the four most prominent schizophrenia candidate genes: Neuregulin1 (NRG1), Dysbindin (DTNBP1), D-amino-acid oxidase activator (DAOA), and D-amino-acid oxidase (DAAO). According to Nicholas Stefanis, the lead author on the paper, their study showed “that apparently normal individuals who posses several risk alleles within these susceptibility schizophrenia genes, have indeed minute decrements in cognitive ability such as decreased attentional capacity and worse performance on memory tasks, and alterations in schizotypal beliefs and experiences.” In other words, they found that the healthy individuals who possessed the risk variants within the DNTBP1, NRG1, and DAAO genes exhibited small reductions in their cognitive performance and had atypical experiences that might be associated with schizophrenia.
How many people have atypical beliefs because they are smart enough to think their way outside the box of the conventional consensus? How many have atypical beliefs because they carry genetic variations that alter the way they view evidence?
Do we as a total society benefit from some people carrying alleles that make them think atypical thoughts? Are smart people with schizophrenia risk genes who do not get schizophrenia more creative, on average, than smart people without these schizophrenia risk genes? Is there some optimal small dose schizophrenia risk alleles that, when combined with high IQ, produces great scientists, inventors, and innovators? Whatever genes made the unusual mind of Vincent Van Gogh might get clipped out of future generations of humanity.
One of my concerns with mental illness risk genes going forward comes from the ability we are gaining to screen and choose amongst our genes to decide what to pass on to our offspring. Will prospective parents take such a risk minimizing approach to offspring genetic allele selection that future generations will have brains that make them more likely to accept the conventional wisdom and to go along with the consensus of elites and masses? Will future societies become more sheepish and less free as a result?
A variation in a gene called GRIK4 appears to make people with depression more likely to respond to the medication citalopram (Celexa) than are people without the variation, a study by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, has found. The increased likelihood was small, but when people had both this variation and one in a different gene shown to have a similarly small effect in an earlier study, they were 23 percent more likely to respond to citalopram than were people with neither variation.
The finding addresses a key issue in mental health research: the differences in people’s responses to antidepressant medications, thought to be based partly on differences in their genes. Some patients respond to the first antidepressant they attempt, but many don’t. Each medication takes weeks to exert its full effects, and patients’ depression may worsen while they search for a medication that helps. Genetic studies, such as the one described here, may lead to a better understanding of which treatments are likely to work for each patient.
The ability to avoid the use of drugs that will fail will reduce time until effective treatments are used and therefore, reduce suffering, speed recovery, and reduce costs.
Genetic variations for serotonin and glutamate neuotransmitter receptors influenced how well people responded to citalopram.
In the newest study, researchers examined the genetic material of more of the patients who had participated in STAR*D, for a total of 1,816 samples, and repeated the comparison of DNA from citalopram responders and nonresponders. They discovered that people with the variation in the GRIK4 gene had a higher likelihood of response, and again found that the variation in the HTR2A gene also made people more likely to respond. The results were reproduced, strengthening their validity.
The protein produced by HTR2A acts as a receptor on brain cells for the chemical messenger serotonin, one of several neurotransmitters that enable the cells to communicate with each other. The discovery that a variation in a serotonin-related gene could affect response to citalopram was not entirely surprising, since the serotonin system is known to be involved in depression. Citalopram targets this system.
But GRIK4 makes a protein that acts as a receptor in a different neurotransmitter system, the glutamate system. Recent studies suggest that the glutamate system also is involved in depression, an assertion supported by the new finding.
Genetic testing for drug selection will also help to avoid drugs that will cause patients side effects. For each drug genetic profiles will be found that put one at much higher risk of adverse reactions,. Everyone will have a complete genetic profile that will help guide drug selection for most effect results with least risk of side effects.
A genetic variant of a neuron adrenergic receptor that binds neurotransmitter noradrenaline boosts recall of emotionally intense memories.
People with a particular gene variant are better at remembering emotionally laden memories than people with the more common version of the gene, research shows. The gene, called ADRA2B, is involved in detecting brain chemicals related to emotional arousal.
The research highlighted the effect of the gene in stark terms: survivors of the 1994 Rwandan genocide were more likely to harbour persistent memories of the conflict if they had the variant version of the gene. The variant is present in 12% of people of African ancestry and in 30% of Causasians.
The researchers showed Swiss and Rwandan experimental subjects pictures with neutral, emotionally negative, and emotionally positive content. Later they had the subjects write down memories of what they saw in the pictures. The Rwandans were refugees living in Uganda who had seen some terrible things in the intertribal kill-fests in Rwanda.
While more Europeans carry the genetic variant that enhances emotionally laden memory recall the Rwandans who had that genetic variant had better recall of negative emotional events.
The researchers found that, in both groups, people carrying the ADRA2B gene variant were "substantially more likely" to remember both positive and negative pictures than people with other forms of the gene. Neutral images were recalled to the same degree by people with and without the variant.
However, Rwandans with the variant had far higher recall of negative emotional events than the Europeans who carried it – and this was unrelated to whether or not they suffered from post traumatic stress disorder.
The Rwandans might have some other genetic variants that work synergistically with ADRB2B to enhance negative memory recall.
Think about the implications. Groups differ in their average tendency to remember bad memories. Does that make some groups and some individuals more likely to hold grudges, seek revenge, and dwell on past events? Do people who better remember bad and good events try harder to set themselves up for repeats of great past events and to avoid repeats of terrible past events? Does this create different cultures in different parts of the world?
As gene testing costs go down by orders of magnitude we are going to see a flood of reports of genetic variations that influence cognitive function in a large variety of ways. The amount of human behavior ascribed to free will is going to shrink. The amount ascribed to current environmental influences will shrink as well.
A new research report in Plos One provides support for the theory that abused children who have low level expression of the gene for monoamine oxidase A (MAOA) are more at risk of becoming violent and anti-social.
Previous research has reported that a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter can moderate the association between early life adversity and increased risk for violence and antisocial behavior. In this study of a combined population of psychiatric outpatients and healthy volunteers (N = 235), we tested the hypothesis that MAOA genotype moderates the association between early traumatic life events (ETLE) experienced during the first 15 years of life and the display of physical aggression during adulthood, as assessed by the Aggression Questionnaire. An ANOVA model including gender, exposure to early trauma, and MAOA genotype as between-subjects factors showed significant MAOA×ETLE (F1,227 = 8.20, P = 0.005) and gender×MAOA×ETLE (F1,227 = 7.04, P = 0.009) interaction effects. Physical aggression scores were higher in men who had experienced early traumatic life events and who carried the low MAOA activity allele (MAOA-L). We repeated the analysis in the subgroup of healthy volunteers (N = 145) to exclude that the observed G×E interactions were due to the inclusion of psychiatric patients in our sample and were not generalizable to the population at large. The results for the subgroup of healthy volunteers were identical to those for the entire sample. The cumulative variance in the physical aggression score explained by the ANOVA effects involving the MAOA polymorphism was 6.6% in the entire sample and 12.1% in the sub-sample of healthy volunteers. Our results support the hypothesis that, when combined with exposure to early traumatic life events, low MAOA activity is a significant risk factor for aggressive behavior during adulthood and suggest that the use of dimensional measures focusing on behavioral aspects of aggression may increase the likelihood of detecting significant gene-by-environment interactions in studies of MAOA-related aggression.
The first report I came across a few years ago on a relationship between low levels of monoamine oxidase A (MAOA), abused children, and violent behavior came from a Dunedin New Zealand twins study. See my post A violence promoting gene and the follow-up and additional related info in the post Serotonin Transporter Gene Linked To Depression, Binge Drinking. Plus, see the post Initial Bullying In Late In Adolescence Causes Most Harm.
What I find interesting about the MAOA variations: The variation that makes one more violent in response to abuse basically makes humans more sensitive to environmental influence. The higher MAOA activity variation makes humans less sensitive to the environment. So the ability of humans to be influenced by the environment is under genetic control.
The fact that genetic variations cause differences in environmental sensitivity has future implications. When offspring genetic engineering enters the realm of the safely doable prospective parents are going to choose against genetic variations that cause environmental sensitivity for behavioral attributes where the parents have strongly held preferences. For example, parents who want total "Goodie Two Shoes" kids are going to choose against genetic variations that create the risk that the kids might turn out violent.
My prediction: Parents will choose genetic variations that make their kids more genetically determined, not less. Parents will choose against genetic variations that put them at 10% risk of some undesired attribute if some other genetic variations would make them at only 1% or a tenth of a percent risk of that the undesirable attribute. Similarly, parents will choose genetic variations that greatly increase the odds of various desired attributes. Basically, genetic variations that leave offspring at moderate odds (say 30% to 70%) of some outcome will get rejected in favor of genetic variations that make attributes either highly likely or highly unlikely.
Minneapolis – April 05, 2007 - A new study in Journal of Personality shows that selfless and social behavior is not purely a product of environment, specifically religious environment. After studying the behavior of adult twins, researchers found that, while altruistic behavior and religiousness tended to appear together, the correlation was due to both environmental and genetic factors.
According to study author Laura Koenig, the popular idea that religious individuals are more social and giving because of the behavioral mandates set for them is incorrect. “This study shows that religiousness occurs with these behaviors also because there are genes that predispose them to it.”
“There is, of course, no specific gene for religiousness, but individuals do have biological predispositions to behave in certain ways,” says Koenig. “The use of twins in the current study allowed for an investigation of the genetic and environmental influences on this type of behavior.”
This research is another example of the way that genes have an impact on behavior. “Society as a whole assumes that home environments have large impacts on behavior, but studies in behavior genetics are repeatedly showing that our behavior is also influenced by our genes,” says Koenig.
Famed University of Minnesota twins researcher Thomas Bouchard is one of the names on the research paper. Koenig is working with experienced twins researchers. Here's an excerpt from the paper's abstract:
In order to investigate this question, religiousness, antisocial behavior, and altruistic behavior were assessed by self-report in a sample of adult male twins (165 MZ and 100 DZ full pairs, mean age of 33 years). Religiousness, both retrospective and current, was shown to be modestly negatively correlated with antisocial behavior and modestly positively correlated with altruistic behavior.
So religious people are both more altruistic and less anti-social on average. This part is interesting. Sounds like the same genetic factors that increase religiousness also increase altruism. What does that tell us about religiousness?
Altruistic behavior also shared most all of its genetic influence, but only half of its shared environmental influence, with religiousness.
My question: Is altruism getting selected for in industrialized societies? I suspect so because religiousness is getting selected for. Also, selfish people are probably less willing to have kids due to all the work entailed.
Also see my post about previous research by Koenig: Twins Study Finds Adult Religiosity Heritable
A professor at the University of Maryland Child Development Laboratory claims the short version of a gene involved in metabolism of neurotransmitter serotonin combined with stress creates a shy kid.
In a study published in the February issue of Current Directions in Psychological Science, Nathan Fox, professor and director of the Child Development Laboratory, and his team found that kids who are consistently shy while growing up are particularly likely to be raised by stressed-out parents, and to possess a genetic variant associated with stress sensitivity.
Like all genes, the particular serotonin-related gene examined in this study has 2 alleles, which can be long or short. The protein produced by the short form of the gene is known to predispose towards some forms of stress sensitivity.
Fox's research found that among children exposed to a mother's stress, it was only those who also inherited the short forms of the gene who showed consistently shy behavior.
"If you have two short alleles of this serotonin gene, but your mom is not stressed, you will be no more shy than your peers as a school age child," says Fox. "But we found that when stress enters the picture, the gene starts to show a strong relationship to the child's behavior," says Fox. "If you are raised in a stressful environment, and you inherit the short form of the gene, there is a higher likelihood that you will be fearful, anxious or depressed."
From this press release we do not know the sample size of his study. But his result is at least plausible.
Suppose this gene's short version works as advertised. When offspring genetic engineering becomes possible will prospective parents choose to make shyness a thing of the past? Will some future generation be anywhere between extroverted and extremely extroverted? If so, what will we lose? My guess is that governments will become more corrupt as people with genetically engineered lack of shyness feel less fear of getting held up to public condemnation.
People are known to differ markedly in their response to sleep deprivation, but the biological underpinnings of these differences have remained difficult to identify. Researchers have now found that a genetic difference in a so-called clock gene, PERIOD3, makes some people particularly sensitive to the effects of sleep deprivation. The findings, reported by Antoine Viola, Derk-Jan Dijk, and colleagues at the University of Surrey's Sleep Research Center, appear online this week in the journal Current Biology, published by Cell Press.
There are two variants of the PERIOD3 gene found in the human population, encoding either long or short versions of the corresponding protein. Each individual will possess two copies of the gene, either of which might be the long or short form. Previous work had indicated that the different forms of the gene appear to influence characteristic morning and evening activity levels—for example, "owl" versus "lark" tendencies.
In the new work, a multidisciplinary research team consisting of biological scientists and psychologists compared how individuals possessing only the longer gene variant and those possessing only the shorter one coped with being kept awake for two days, including the intervening night. The researchers found that although some participants struggled to stay awake, others experienced no problems with the task.
The results were most pronounced during the early hours of the morning (between 4 and 8 a.m.), during which individuals with the longer variant of the gene performed very poorly on tests for attention and working memory.
But how do the carriers of the short and long versions perform during the day when they have plenty of sleep?
Carriers of the longer version spent a larger portion of their sleep time in the deepest sleep state. My guess is that confers some sort of advantage. Any idea what that advantage might be?
An additional finding was that the effects of this gene on performance may be mediated by its effects on sleep. When the volunteers were allowed to sleep normally, those possessing only the longer form of the gene spent about 50% more of their time in slow-wave sleep, the deepest form of sleep. Slow-wave sleep is a marker of sleep need, and it is known that carrying a sleep debt makes it very difficult to stay awake and perform at night.
What I'd like to know: Do the people with the longer form of the gene form more memories when they sleep? I ask this because if there are two versions of the gene widespread then likely each version provides advantages and disadvantages. What advantage does the long version provide that compensates for its disadvantages when one stays up all night?
When offspring genetic engineering becomes possible prospective parents are going to be faced with thousands or even tens of thousands of trade-offs between different genetic variations for their offspring. Make your kid a night owl? Or make him wake up at the crack of dawn? Make your kid able to handle lots of sleep disruptions and get by on less sleep? Or perhaps make her brain age more slowly or form more memories per time asleep?
BUDAPEST, HUNGARY, March 9 – Ever wonder why some women seem to be more ill-tempered than others? University of Pittsburgh researchers have found that behaviors such as anger, hostility and aggression may be genetic, rooted in variations in a serotonin receptor gene. Indrani Halder, Ph.D., of the Cardiovascular Behavioral Medicine Program at the University of Pittsburgh, will present the findings today at the American Psychosomatic Society's Annual Meeting, held in Budapest, Hungary.
Previous studies have associated the hormone serotonin with anger and aggression in both humans and animals and have shown that increased serotonin activity is related to a decrease in angry and aggressive behaviors. In the study being presented today, researchers sought to determine if this relationship was genetically determined. The study is the first to look at the relationship between variations in the serotonin receptor 2C gene and anger and hostility.
Completed at the University of Pittsburgh's Behavioral Physiology Laboratory, the study looked at 550 unrelated women of European descent. In order to find normal variations in genes and behavior, the women were not prescreened for behavioral type. Researchers found that those who had one or both of two alterations in the promoter region of the serotonin receptor 2C gene were more likely to score lower on two common tests for anger, hostility and aggression.
But not so fast. Robert Plomin, who has spent years trying to find gene alleles that produce differences in intelligence, thinks the search for genes that influence cognitive qualities is so hard that these latest results are unlikely to be correct.
"Individual differences in aggression and anger are influenced by genes -- as are all personality traits -- but progress in identifying the genes has been slower than researchers expected," added Prof Robert Plomin, deputy director of the Social, Genetic and Development Psychiatry Centre, London. "Thousands of reports of this gene or that gene being related to complex traits or common disorders in the end fail to replicate, not just for behaviour but also for medical problems such as dementia and heart disease."
I am very keen to find out which genetic variations create differences in personality, intelligence, and other aspects of cognitive function. But since Plomin and other scientists think each mental trait is controlled by many gene alleles and each variation contributes only a small amount to the total result. So identifying a genetic influence above the background noise of other genetic variations and environmental influences is very difficult.
The solution to this problem? Huge decreases in the cost of DNA testing. Gene chips that test hundreds of thousands of single letter DNA differences at once have already hit the market quite recently. We need gene testing cheap enough that thousands or tens of thousands of genetic variations can be checked in each person in a study. We also need costs so low that thousands or even tens of thousands of people can get checked at once. Then scientists will be able to control for enough genetic variations at once to identify those that are really influencing cognitive function.
We are waiting for advances in gene chip and microfluidics biotechnology so that scientific questions about human genomes become easy to answer. Most of what we are going to learn about human genetic differences is going to be figured out in a short period of time after decades of attempts to answer those questions. The instrumentation advances are more important than any one or ten of the scientific discoveries that will come from them.
Most people inherit a version of a gene that optimizes their brain's thinking circuitry, yet also appears to increase risk for schizophrenia, a severe mental illness marked by impaired thinking, scientists at the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) have discovered. The seeming paradox emerged from the first study to explore the effects of variation in the human gene for a brain master switch, DARPP-32.
The researchers identified a common version of the gene and showed how it impacts the way two key brain regions exchange information, affecting a range of functions from general intelligence to attention.
If higher intelligence was a longer running trait in the human species it is unlikely that we'd have IQ-boosting genetic variations that come with such serious downsides. Bad side effects of genes that provide some benefit are usually a sign that the genetic adaptation in question is a recent response to a recent selective pressure.
Three fourths of subjects studied had at least one copy of the version that results in more efficient filtering of information processed by the brain's executive hub, the prefrontal cortex. However, the same version was also more prevalent among people who developed schizophrenia, a severe mental illness marked by delusions, hallucinations and impaired emotion that affects one percent of the population.
"We have found that DARPP-32 shapes and controls a circuit coursing between the human striatum and prefrontal cortex that affects key brain functions implicated in schizophrenia, such as motivation, working memory and reward related learning," explained Andreas Meyer-Lindenberg, M.D.
"Our results raise the question of whether a gene variant favored by evolution, that would normally confer advantage, may translate into a disadvantage if the prefrontal cortex is impaired, as in schizophrenia," added Daniel Weinberger, M.D. "Normally, enhanced cortex connectivity with the striatum would provide increased flexibility, working memory capacity and executive control. But if other genes and environmental events conspire to render the cortex incapable of handling such information, it could backfire -- resulting in the neural equivalent of a superhighway to a dead-end."
I expect when offspring genetic engineering becomes widespread people will have to face many tough questions about how to weigh the benefits and risks of large numbers of genetic variations they could give their offspring. Some humans are not cognitively well designed to model complex trade-offs that involve probabilities I expect a lot of bad decision-making by prospective parents.
A study on twins and their offspring provides another chunk of evidence that the effect of environment has been overrated. The parents fight because it is in their genes to do so and so their kids behave poorly due to the same genes.
Children's conduct problems--skipping school, sneaking out of the house, lying to parents, shoplifting, or bullying other children--are a major source of concern for parents and teachers. As a potential cause of these problems, parents' marital conflict has received a lot of research attention. Now a new study finds that parents' fighting may not be to blame but rather that parents who argue a lot may pass on genes for disruptive behavior to their children.
The findings are published in the January/February 2007 issue of the journal Child Development.
A group of researchers from the University of Virginia and several other universities looked at this question, studying 1,045 twins and their 2,051 children. Some of the parents were identical twins and shared all of their genes and some were fraternal and shared only half of their genes. The study found that parents' fighting is not likely a cause of children's conduct problems. On the other hand, parents' genes influenced how often they argued with their spouses and these same genes, when passed to their children, caused more conduct problems.
"This study suggests that marital conflict is not a major culprit, but genes are," said K. Paige Harden, the lead researcher and professor of psychology at the University of Virginia. "Our findings have potential implications for treating conduct problems: Focusing on a child's parents, as is common in family therapy, may not be as effective as focusing on the child."
So if your kids are bad you and your spouse are still to blame. But you are to blame for your genes, not for your behavior.
What I want to know: When offspring genetic engineering becomes possible will people who tend to have low triggers for violence decide to edit out the genetic sequences that cause this when choosing genes for their offspring? Or will they give their kids even stronger doses of the genes that make them carry on yelling and screaming and fighting?
The completion of the Allen Institute for Brain Science's inaugural project signals a remarkable leap forward in one of the last frontiers of medical science -- the brain.
The Institute today announced the completion of the groundbreaking Allen Brain Atlas, a Web-based, three-dimensional map of gene expression in the mouse brain. Detailing more than 21,000 genes at the cellular level, the Atlas provides scientists with a level of data previously not available.
Since humans share more than 90 percent of their genes with mice, the Atlas offers profound opportunity to further understanding of human disorders and diseases such as Alzheimer's, Parkinson's, epilepsy, schizophrenia, autism and addiction. About 26 percent of American adults -- close to 58 million people -- suffer from a diagnosable mental disorder in a given year.
Many human brain diseases have mouse equivalents developed using genetic engineering on lab mice. As the cost of measuring gene activity drops a logical next step would be to repeat this work using mice which have a variety of brain disorders.
You can access the Brain Atlas for free online.
"This project is an unprecedented union of neuroscience and genomics," said philanthropist and Microsoft co-founder Paul G. Allen, who provided $100 million in seed money to launch the Allen Institute for Brain Science and its first project, the Allen Brain Atlas, in 2003. "The comprehensive information provided by the Atlas will help lead scientists to new insights and propel the field of neuroscience forward dramatically."
Publicly available at no cost, the map shows which genes are active -- or "expressed" -- within the brain and which regions and cells they are expressed in, thereby linking them to particular brain functions.
The brain uses most of the genome.
The project has already led to several significant new findings about the brain. It reveals that 80 percent of genes are turned on in the brain, much higher than the 60 to 70 percent scientists previously believed.
It indicates that very few genes are turned on in only one region of the brain -- paving the way for additional insight about the benefits and potential side effects of drug treatments. And it shows the location of genes associated with specific functions, providing scientists with valuable information about regional brain activity.
Many brain scientists use the Atlas.
Even before its announced completion, the Atlas was receiving more than 4 million hits monthly and being accessed by approximately 250 scientists on any given work day. Users are not required to provide information about their work, but anecdotal evidence indicates that the Atlas is already assisting research projects.
"I use it around the clock, night and day. My whole lab does," said Stanford University neurobiology professor Ben A. Barres, who is using the Atlas to confirm his team's findings about glial cells, a type of non-neuronal cell within the nervous system.
"It's completely essential. It's saved us years and years of work, maybe decades. We could never have done all this, either financially or in terms of the amount of labor and time. It was just so incredibly generous of Mr. Allen to do this, and I think it's hard to even overstate what the payoff is going to be for research."
Researchers at the Allen Institute created the database using a process known as in-situ hybridization. A mouse brain is sliced into thin layers and then labeled with a DNA "probe" that binds only to a single gene, highlighting the expression pattern for that gene.
In-situ maps were made for every gene in the mouse genome, then loaded into a massive database. To complete the entire database, researchers processed 170 genes per day, and produced some 1,000 gigabytes of data each day. The finished atlas cost about $41 million to produce.
The development of gene array chips and other technologies for measuring many parts of a biological system at once look set to continue to accelerate the rate at which scientists can collect information from cells and organisms. The Brain Atlas couldn't have been developed 10 years ago. 10 years from now we'll have still more orders of magnitude improvement in the ability to measure and collect data on the activites inside cells and organisms.
The next project, Jones said, will be to develop a digital, three-dimensional, interactive map of the genes at work in a human brain's neocortex, the outer layer that is the seat of higher thought and emotion, using brains from cadavers as well as tissue removed during brain surgeries.
We are coming to the end of the dark ages of how the human brain works.
Some people spend their whole lives in search of happiness and escape from a feeling of hopelessness and ennui. They lack the technology that would grant them immediate satisfaction. Knock out a gene and be happy.
A new breed of permanently 'cheerful' mouse is providing hope of a new treatment for clinical depression. TREK-1 is a gene that can affect transmission of serotonin in the brain. Serotonin is known to play an important role in mood, sleep and sexuality. By breeding mice with an absence of TREK-1, researchers were able create a depression-resistant strain. The details of this research, which involved an international collaboration with scientists from the University of Nice, France, are published in Nature Neuroscience this week.
"Depression is a devastating illness, which affects around 10 percent of people at some point in their life," says Dr. Guy Debonnel an MUHC psychiatrist, professor in the Department of Psychiatry at McGill University, and principal author of the new research. "Current medications for clinical depression are ineffective for a third of patients, which is why the development of alternate treatments is so important."
Mice without the TREK-1 gene ("knock-out" mice) were created and bred in collaboration with Dr. Michel Lazdunski, co-author of the research, in his laboratory at the University of Nice, France. "These 'knock-out' mice were then tested using separate behavioral, electrophysiological and biochemical measures known to gauge 'depression' in animals," says Dr. Debonnel. "The results really surprised us; our 'knock-out' mice acted as if they had been treated with antidepressants for at least three weeks."
One of the reasons I watch for mouse gene knock-out studies is that they are a glimpse into the choices prospective parents (and domineering governments) will face when it becomes possible to tinker with the DNA of eggs, sperm, and embryos. In the future some people will opt for offspring genetic engineering to make their kids congenitally happy uncurable optimists. Other people will genetically engineer their kids to be highly objective analytical realists. Not a few of the latter will want to come up with ways to infect the obnoxiously optimistic with viruses that will reprogram them for more realism and less optimism.
Other future parents will opt for drugs instead of genetic engineering to make their kids happy, calm, content, and confident. Make Johnny and Jill grow up as joyful kids but then tell them at age 18 they just have to stop taking the pills and they'll be able to suffer all the doubts, depression, and sadness that the older generations experienced.
Gene knock-out studies also provide glimpses into just how little free will we have (if we even have any at all).
The discoveries from gene knock-out studies will become a torrent when efforts to create mice with gene knock-outs for each mouse gene achieve their goals.
Genetic causes of behavior matter because they influence us right now. But they will matter even more in the future when offspring genetic engineering becomes a reality. I think it unlikely that people will consciously choose the same frequencies of genetic variations for their offspring as occur naturally. Every human nature that has some genetic causes is going to become either more or less frequent when people can choose which genetic variations to give their offspring. Hence every report about genetic causes of some human behavior is a report about something humans do that they'll become either more or less inclined to do in the future. Will parents choose to use genetic engineering make their kids more entrepreneurial?
Scott Shane, the Mixon Professor of Entrepreneurial Studies at Case Western Reserve University's Weatherhead School of Management; Nicos Nicolaou, a lecturer in entrepreneurship at the Tanaka School of Business of Imperial College London; and Janice Hunkin, Lynn Cherkas, and Tim Spector of the Twin Research & Genetic Epidemiology Unit at St Thomas' Hospital in London, home of the UK Twin registry of over 10,000 twins collaborated in this unique study. They compared rates of entrepreneurship between and among more than 1,200 pairs of identical and fraternal twins in the U.K and conclude that nearly half—48 percent—of an individual's propensity to become self-employed is genetic.
The authors studied self-employment among 609 pairs of identical twins, and compared it to self-employment among 657 pairs of same-sex fraternal twins in the U.K. Identical twins share 100% of their genetic composition, while fraternal twins share about 50%, on average. Thus differences in the rates at which pairs of identical twins both become entrepreneurs and the rates at which both members of fraternal twins both become entrepreneurs are attributable to genetics. "One can look at the patterns of concordance (the numbers of pairs of twins in which both members are or are not entrepreneurs) and reasonably infer that genetic factors account for the differences," says Shane.
The authors propose several methods by which genetic factors might influence people's tendency to become entrepreneurs. For example, genes may predispose an individual to develop traits such as being sociable and extroverted, which in turn facilitate skills such as salesmanship, which are vital to entrepreneurial success.
In addition, genes have been shown to affect the level of education an individual receives, and more highly educated people are likelier to become entrepreneurs because they are better able to recognize new business opportunities when they arise.
It is likely that entrepreneurship comes as a result of other qualities as mentioned above. Will parents choose those qualities based on a desire to make their kids self-employed? Or will they choose those qualities mainly for other reasons and will the effect on entrepreneurial behavior come as a side effect of choices made for other reasons?
People in different cultures, economic classes, occupations, religions, and with different genetically determined qualities for their own minds will make different choices on average. Will this tend to make the human race diverge? Or will there be a wide consensus on all the important genetically controlled qualities of the mind and will humanity tend to converge?
One split I expect: I predict some religious folks will choose genetic qualities that make their kids more inclined to have faith. Whereas more empirically minded folks will choose genetic qualities that make their kids highly skeptical, critical, and empirical. Though some of a more socialistic bent might choose qualities that make kids turn out more altruistic and group-oriented.
Scientists at the National Institutes of Health’s (NIH) National Institute on Alcohol Abuse and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individual’s risk for obsessive-compulsive disorder (OCD). The new functional variant, or allele, is a component of the serotonin transporter gene (SERT), site of action for the selective serotonin reuptake inhibitors (SSRIs) that are today’s mainstay medications for OCD, other anxiety disorders, and depression.
“Improved knowledge of SERT‘s role in OCD raises the possibility of improved screening, treatment, and medications development for that disorder,” said Ting-Kai Li, M.D., Director, National Institute on Alcohol Abuse and Alcoholism. “It also provides an important clue to the neurobiologic basis of OCD and the compulsive behaviors often seen in other psychiatric diseases, including alcohol dependence.”
Approximately 2 percent of U.S. adults (3.3 million people) have OCD, the fourth most prevalent mental health disorder in the United States. Individuals with OCD have intrusive, disturbing thoughts or images (obsessions) and perform rituals (compulsions) to prevent or banish those thoughts. Many other individuals demonstrate obsessive-compulsive behaviors that do not meet OCD diagnostic criteria but alter the individuals’ lives.
Drs. David Goldman, Chief, and Xianzhang Hu, Research Scientist, in NIAAA’s Laboratory of Neurogenetics discovered the linkage aided by new functional analyses of the SERT genetic variant. The researchers first compared the genotypes of 169 OCD patients to those of 253 controls in a large U.S. patient population[i] and found that the OCD patients were twice as likely to have the variant. Then they studied transmission and non-transmission of the variant in a Canadian population[ii] of 175 OCD parent-child trios (two healthy parents and a child with OCD) and found that the risk variant was twice as likely to be transmitted from a parent to a child with OCD. Specifically, of 86 informative trios, 48 children carried the new risk variant and 26 did not.
Not surprisingly considering this result Stanford researchers found that a serotonin selective reuptake inhibitor, citalopram, provides some relief from OCD.
The pace of genetic studies like the one above happen at a rate mostly driven by the cost of DNA sequencing. When DNA sequencing costs fall orders of magnitude further then scientists will able able to perform massive comparisons of gene sequences between people with and without a large number of disorders and diseases. This will lead to the discovery of large numbers of other genetic variations that influence cognitive function and the risk of cognitive and other disorders.
People are going to become far more interested in the sequences of other people once we know how many different genetic variations influence behavior. Companies will want to hire managers with genetic profiles that mark them as bound to perform well. Ditto for engineers, sales reps, and other types of workers.
Also see my previous posts "Gene Mutations Cause Rare Form Of Obsessive Compulsive Disorder" and "Compulsive Hoarders Have Unique Brain Scan Patterns".
Variations in the enzyme Monoamine Oxidase-A (which breaks down neurotransmitters such as serotonin) have been previously found to affect whether abuse as a child causes greater tendency toward anti-social behavior and violence. Now some researchers have looked at brains with the two different MAO-A variations and found that people with the short variation of MAO-A have less brain gray matter in an area that regulates mood.
The gene is one of two common versions that code for the enzyme monoamine oxydase-A (MAO-A), which breaks down key mood-regulating chemical messengers, most notably serotonin. The previously identified violence-related, or L, version, contains a different number of repeating sequences in its genetic code than the other version (H), likely resulting in lower enzyme activity and hence higher levels of serotonin. These, in turn, influence how the brain gets wired during development. The variations may have more impact on males because they have only one copy of this X-chromosomal gene, while females have two copies, one of which will be of the H variant in most cases.
Several previous studies had linked increased serotonin during development with violence and the L version of MAO-A. For example, a 2002 study* by NIMH-funded researchers discovered that the gene’s effects depend on interactions with environmental hard knocks: men with L were more prone to impulsive violence, but only if they were abused as children. Meyer-Lindenberg and colleagues set out to discover how this works at the level of brain circuitry.
Using structural MRI in 97 subjects, they found that those with L showed reductions in gray matter (neurons and their connections) of about 8 percent in brain structures of a mood-regulating circuit (cingulate cortex, amygdala) among other areas. Volume of an area important for motivation and impulse regulation (orbital frontal cortex) was increased by 14 percent in men only. Although the reasons are unknown, this could reflect deficient pruning — the withering of unused neuronal connections as the brain matures and becomes more efficient, speculates Meyer-Lindenberg.
The researchers then looked at effects on brain activity using functional MRI (fMRI) scans. While performing a task matching emotionally evocative pictures — angry and fearful faces — subjects with L showed higher activity in the fear hub (amygdala). At the same time, decreased activity was observed in higher brain areas that regulate the fear hub (cingulate, orbital frontal, and insular cortices) — essentially the same circuit that was changed in volume.
While these changes were found in both men and women, two other experiments revealed gene-related changes in men only. In a task which required remembering emotionally negative information, men, but not women, with L had increased reactivity in the fear (amygdala) and memory (hippocampus) hubs. Men with L were also deficient during a task requiring them to inhibit a simple motor response; they failed to activate a part of the brain (cingulate cortex) important for inhibiting such behavioral impulses. This region was, conspicuously, the cortex area that was most reduced in volume.
The findings echo those of a 2005 NIMH study** showing how another serotonin-related gene variant shapes the same mood-regulating circuit. In this study also, the gene version that boosts serotonin levels resulted in impaired emotion-related lower brain structures, increased fear hub activation and a weaker response of its regulatory circuits. Yet, the effects of the L version of MAO-A were more extensive, perhaps reflecting the fact that it also impacts another key mood-regulating neurotransmitter, norepinephrine.
The weakened regulatory circuits in men with L are compounded by intrinsically weaker connections between the orbital frontal cortex and amygdala in all men, say the researchers.
Next time someone tries to punch you out in a bar just calmly explain to him that he's only trying to beat you up because he doesn't have enough gray matter in his cingulate cortex and amygdala.
Do you believe in free will? I'm sure that there's some set of genetic variations that cause you to think such a thought.
LA JOLLA – Brains are marvels of diversity: no two look the same -- not even those of otherwise identical twins. Scientists at the Salk Institute for Biological Studies may have found one explanation for the puzzling variety in brain organization and function: mobile elements, pieces of DNA that can jump from one place in the genome to another, randomly changing the genetic information in single brain cells. If enough of these jumps occur, they could allow individual brains to develop in distinctly different ways.
This result might explain why humans differ in their intellectual abilities and behavioral tendencies in ways that are not accounted for by genetic inheritance or environment. Humans may end up being even more controlled by their genes than twins studies would suggest because some of the genetic patterns that control them are generated during fetal development.
"This mobility adds an element of variety and flexibility to neurons in a real Darwinian sense of randomness and selection," says Fred H. Gage, Professor and co-head of the Laboratory of Genetics at the Salk Institute and the lead author of the study published in this week's Nature. This process of creating diversity with the help of mobile elements and then selecting for the fittest is restricted to the brain and leaves other organs unaffected. "You wouldn't want that added element of individuality in your heart," he adds.
Precursor cells in the embryonic brain, which mature into neurons, look and act more or less the same. Yet, these precursors ultimately give rise to a panoply of nerve cells that are enormously diverse in form and function and together form the brain. Identifying the mechanisms that lead to this diversification has been a longstanding challenge. "People have speculated that there might be a mechanism to create diversity in brain like there is in the immune system, and the immune system's diversity is perhaps the closest analogy we have," says Gage.
The researchers were aware that the immune system rather systematically reshuffles antibody genes to produce a large variety of immune cells that make many different antibodies for different antigens it might encounter.
In the immune system, the genes coding for antibodies are shuffled to create a wide variety of antibodies capable of recognizing an infinite number of distinct antigens.
In their study, the researchers closely tracked a single human mobile genetic element, a so-called LINE-1 or L1 element in cultured neuronal precursor cells from rats. Then they introduced it into mice. Every time the engineered L1 element jumped, the affected cell started glowing green [WHY?]. "We were very excited when we saw green cells all over the brain in our mice," says research fellow and co-author M. Carolina N. Marchetto, "because then we knew it happened in vivo and couldn't be dismissed as a tissue culture artifact."
Transposable L1 elements, or "jumping genes" as they are often called, make up 17 percent of our genomic DNA but very little is known about them. Almost all of them are marooned at a permanent spot by mutations rendering them dysfunctional, but in humans a hundred or so are free to move via a "copy and paste" mechanism. Long dismissed as useless gibberish or "junk" DNA, the transposable L1 elements were thought to be intracellular parasites or leftovers from our distant evolutionary past.
It has been known for a long time that L1 elements are active in testis and ovaries, which explains how they potentially play a role in evolution by passing on new insertions to future generations. "But nobody has ever demonstrated mobility convincingly in cells other than germ line cells," says Gage.
Apart from their activity in testis and ovaries, jumping L1 elements are not only unique to the adult brain but appear to happen also during early stages of the development of nerve cells. The Salk team found insertions only in neuronal precursor cells that had already made their initial commitment to becoming a neuron. Other cell types found in the brain, such as oligodendrocytes and astrocytes, were unaffected.
At least in the germ line, copies of L1s appear to plug themselves more or less randomly into the genome of their host cell. "But in neuronal progenitor cells, these mobile elements seem to look for genes expressed in neurons. We think that's because when the cells start to differentiate the cells start to open up genes and expose their DNA to insertions," explains co- author Alysson R. Muotri. "What we have shown for the first time is that a single insertion can mess up gene expression and influence the function of individual cells," he adds.
However, it is too early to tell how often endogenous L1 elements move in human neurons and how tightly this process is regulated or what happens when this process goes awry, cautions Gage. "We only looked at one L1 element with a marker gene and can only say that motility is likely significantly more for endogenous L1 elements," he adds.
Maybe some mental illnesses are caused by L1 elements inserting in places where they mess up the functioning of some brain neurons.
If I'm right in my suspicion that this result shows how we could be even more genetically determined than twins studies suggest then we are genetically determined in ways that introduce randomness at an early stage of brain development. This leaves even less room for social environment to influence development. Eventually biotechnological means will be found to reduce the degree of randomness in the L1 insertions so that outcomes of the development of offspring will become more predictable. See my post Children Of The Future May Be More Genetically Determined for further elaboration of that argument.
The idea of jumping genes in our brains triggers a memory of Mark Twain's The Notorious Jumping Frog of Calaveras County. Seems faintly related because the genes jumping around in our brains seem whimsical. Oh, and for some reason unknown to me the story is also known as The Celebrated Jumping Frog of Calaveras County. So which title was the original?
ATLANTA - Why are some people shy while others are outgoing? A study in the current issue of Science demonstrates for the first time that social behavior may be shaped by differences in the length of seemingly non-functional DNA, sometimes referred to as junk DNA. The finding by researchers at the Yerkes National Primate Research Center of Emory University and the Atlanta-based Center for Behavioral Neuroscience (CBN) has implications for understanding human social behavior and disorders, such as autism.
In the study, Yerkes and former CBN graduate student Elizabeth A.D. Hammock, PhD, and Yerkes and CBN researcher Larry J. Young, PhD, also of the Department of Psychiatry and Behavioral Sciences at Emory University's School of Medicine, examined whether the junk DNA, more formally known as microsatellite DNA, associated with the vasopressin receptor gene affects social behavior in male prairie voles, a rodent species. Previous studies, including Dr. Young's gene-manipulation study reported in Nature's June 17, 2004, issue, have shown the vasopressin receptor gene regulates social behaviors in many species.
The researchers bred two groups of prairie voles with short and long versions of the junk DNA. By comparing the behavior of male offspring after they matured, they discovered microsatellite length affects gene expression patterns in the brain. In the prairie voles, males with long microsatellites had higher levels of vasopressin receptors in brain areas involved in social behavior and parental care, particularly the olfactory bulb and lateral septum. These males spent more time investigating social odors and approached strangers more quickly. They also were more likely to form bonds with mates, and they spent more time nurturing their offspring.
I picture women who want their men to stay faithful some day surreptitiously injecting gene therapy into neck arteries of sleeping boyfriends or husbands to reprogram their microsatellite DNA to longer lengths around the vasopressin gene. And here's the twist: If the guy discovers he has been reprogrammed by his woman he'll be so attached to her that he won't want to leave her because of it.
"This is the first study to demonstrate a link between microsatellite length, gene expression patterns in the brain and social behavior across several species," said Young. "Because a significant portion of the human genome consists of junk DNA and due to the way microsatellite DNA expands and contracts over time, microsatellites may represent a previously unknown factor in social diversity."
Hammock and Young's finding extends beyond social diversity in rodents to that in apes and humans. Chimpanzees and bonobos, humans' closest relatives, have the vasopressin receptor gene, yet only the bonobo, which has been called the most empathetic ape, has a microsatellite similar to that of humans. According to Yerkes researcher Frans de Waal, PhD, "That this specific microsatellite is missing from the chimpanzee's DNA may mean the last common ancestor of humans and apes was socially more like the bonobo and less like the relatively aggressive and dominance-oriented chimpanzee."
The researchers' finding also has set a clear course for the next step. They want to build upon previous studies that identified a microsatellite sequence in the human vasopressin receptor that varies in length. "The variability in the microsatellite could account for some of the diversity in human social personality traits," explains Hammock. "For example, it may help explain why some people are naturally gregarious while others are shy." In particular, Young wants his research team to expound upon studies that have identified a link with autism.
Research in prairie voles has provided evidence about vasopressin effects on pair bonding in prairie voles that led to the discovery that pair bonding in humans involves some of the same brain areas as are seen in prairie voles. It is not far fetched to take the discovery of vasopressin receptor microsatellite DNA's role behavior in prairie voles as a reason to look for similar DNA in humans playing a regulatory role in human behavior.
The researchers first showed in cell cultures that the vole vasopressin receptor microsatellites could modify gene expression. Next, they bred two strains of a monogamous species, the prairie vole – one with a long version of the microsatellites and the other with a short version. Adult male offspring with the long version had more vasopressin receptors in brain areas involved in social behavior and parenting (olfactory bulb and lateral septum). They also checked out female odors and greeted strangers more readily and were more apt to form pair bonds and nurture their young.
"If you think of brain circuits as locked rooms, the vasopressin receptor as a lock on the door, and vasopressin as the key that fits it, only those circuits that have the receptors can be 'opened' or influenced by the hormone," added Hammock. "An animal's response to vasopressin thus depends upon which rooms have the locks and our research shows that the distribution of the receptors is determined by the length of the microsatellites."
Prairie voles with the long version have more receptors in circuits for social recognition, so release of vasopressin during social encounters facilitates social behavior. If such familial traits are adaptive in a given environment, they are passed along to future generations through natural selection.
Variability in vasopressin receptor microsatellite length could help account for differences in normal human personality traits, such as shyness, and perhaps influence disorders of sociability like autism and social anxiety disorders, suggest the researchers.
Will humans choose to biologically engineer their male offspring to be much more social? If future generations of men want to gossip endlessly about human relations this could be a problem for those of us with natural male brains. If due to rejuvenation therapies I live to see society dominated by highly social males I'm going to found a club of old style men who can hang around and talk about cars or airplanes or anything else for that matter. Or better yet, go through long periods of not talking at all.
Dr. Essi Viding of the London Kings College Institute of Psychiatry and colleagues have found the tendency toward psychopathic behavior has a strong genetic component. (same press release here)
New research on the origins of antisocial behaviour, published in the Journal of Child Psychology and Psychiatry, suggests that early-onset antisocial behaviour in children with psychopathic tendencies is largely inherited.
...Dr Viding's research looked into the factors that contribute to antisocial behaviour in children with and without psychopathic tendencies. By studying sets of 7-year-old twins, Dr. Viding and her colleagues were able to pinpoint to what extent antisocial behaviour in these two groups was caused by genetic and/or environmental risk factors.
A sample of 3687 twin pairs formed the starting point for this research. Teacher ratings for antisocial behaviour and psychopathic tendencies (i.e. lack of empathy and remorse) were used to classify the twins. Those who were in the top 10% of the sample for antisocial behaviour were separated into two groups - those with and without psychopathic tendencies.
Following analysis, the results showed that, in children with psychopathic tendencies, antisocial behaviour was strongly inherited. In contrast, the antisocial behaviour of children who did not have psychopathic tendencies was mainly influenced by environmental factors. These findings are in line with previous research showing that children with psychopathic tendencies are at risk to continue their antisocial behaviour and are often resistant to traditional forms of intervention.
For those who recognize the name note that Robert Plomin is one of the co-authors.
Evidence for substantial genetic risk for psychopathy in 7-year-olds (Essi Viding, R. James R. Blair, Terrie E. Moffitt, Robert Plomin) is published in the June 2005 issue of The Journal of Child Psychology and Psychiatry.
Preliminary findings from the Twins Early Development Study (TEDS) indicate that within the early-onset group there are at least two etiologically distinct groups of children. Antisocial behavior in 7-year-old children with callous and unemotional traits is under strong genetic influence, whereas antisocial behavior in children without such personality traits is primarily environmentally mediated.
Such findings of etiological differences are prompting the search for risk genes, as well as highlighting the need to study environmental risk within a genetic framework. It must be emphasized that high heritability is not equivalent to immutability. Better understanding of gene-environment interactions can come to inform successful prevention programs that target young children. These prevention programs may well be different for etiologically distinct subgroups of children at risk for violent and antisocial outcomes.
Twin studies can help distinguish between genetic and environmental determinants of violence, said Essi Viding of the Institute of Psychiatry in London. In antisocial 7-year-olds with callous and unemotional traits, Viding found, the antisocial behavior was strongly genetic in origin (a group heritability of 80%). If these youths can be identified early, perhaps with a genetic test on cells from a cheek swab, one could target programs for them. "Genes are not a blueprint that determines outcome," said Viding. "Rather, they act together with other risk or protective factors to increase or reduce the risk of disorder."
Antisocial behavior and physical violence, it turns out, are moderately heritable. A recent meta-analysis of behavioral genetic studies estimated that 41% of the variance on antisocial behavior is due to genetic factors, about 16% to shared environmental factors, and about 43% to nonshared environmental factors.
Viding's group is currently trying to find genes associated with callous-unemotional traits. If such genes can be identified, the researchers can explore how environment affects the outcomes of children who carry the genes. For example, they may be able to see whether the same genes place children at risk for both antisocial behavior and hyperactivity. They may also be able to assess how risk genes interact with risk environments throughout development.
Genes are not a blueprint that determines outcome. Genes alone are neither sufficient, nor necessary, in causing the antisocial behavior.
I am highly skeptical of claims that genes alone are never sufficient to cause antisocial behavior. Certainly some genotypes make people more at risk of being violent or antisocial only in response to specific types of environmental influences. But surely other genotypes must make other children born "bad to the bone". Claims that environmental interventions can always override genetic influences strike me as denial. Sorry, sometimes the genome wins.
To put my argument another way: Some people are more genetically determined than others. (and I predict people will become more genetically determined in the future) Some people have genes that make them highly susceptible to programming by environmental influences. But others have genes that make them highly resistant to various types of environmental influences. For example, some people are going to be happy or unhappy regardless of their environment. Others will have moods and motivations that are greatly influenced by disappointments or good fortune. Some will become violent as a result of child abuse. Others will stay pacifist no matter how much abuse they suffer.
Also, in some cases where genes make someone highly susceptible to environmental influences the effect is to make that person more prone to become criminal or otherwise problematic for the rest of us. Genes can make a person prone to going down an undesirable developmental path or so prone to antisocial behavior that without taking some rather severe steps to isolate such people from "the slings and arrows of outrageous misfortune" some of them are going to go over to the "dark side of the force". The degree to which they can be triggered by environmental stimuli is so great that the ability of environment to influence them is not a reason for optimism.
Even in cases where one twin becomes a psychopath and the other does not become a psychopath that is not automatic proof that therefore social environment made the difference. Some part of deveopmental outcome is due to random noise. Genes do not perfectly control development. Hardwired differences in brains of twins will be present at birth due to chance. Throw in additional noise in very early childhood and before many social influences are felt genetic and non-genetic but developmentally caused and irreversible (at least with current biotechnology) differences will already be well established.
Genes control the extent to which a person is susceptible to various events in the environment and genes exercise great influence over how a person will respond to abuse as a child or a threat uttered in a bar or other events in a person's life. Genes even control the extent to which developmental outcomes are due to random noise from the environment and from Brownian motion. Hopes that socialization can always compensate for genetic inheritance to prevent antisocial thought patterns and behavior strike me as hopelessly naive.
Once psychopathy as a genetically caused condition becomes accepted and genetic testing and genetic engineering becomes possible do you favor or oppose the use of either genetic testing (for selective abortion) or genetic engineering (perhaps delivered in utero) to prevent the development of psychopaths? Consider your other choices. Early and lifetime institutionalization of kids who are bad to the bone would prevent them from preying on others but conflict with the assumption of "innocent until one has committed a crime", let alone "innocent until proven guilty". The other option is what we do now: let those kids grow up and victimize people before being caught committing crimes. That latter option consigns some people to future victimhood and, worse yet, not all psychopaths are ever caught by the criminal justice system. "Successful psychopaths" with an increased corpus callosum but with a symmetrical hippocampus are much less likely to get caught by the police than psychopaths that also have an asymmetrical hippocampus.
Suppose early environmental conditioning techniques which can reverse psychopathy are discovered. Parentheticaly I'm extremely skeptical of the notion than any socialization practices can counteract the effects of gross differences in brain morphology characteristic of psychopaths. But suppose I'm wrong. Would you favor removing a very young budding psychopath from his parents in order to put him through a social conditioning therapy to reverse his psychopathy?
A German team has found that congenital prosopagnosia (CP), a conditon where a person has a hard time recognizing faces, is genetically inherited. Thomas Grüter, himself a CP sufferer, and his team at the Institute for Human Genetics in Münster, Germany traced CP in 7 families and found evidence that CP is inherited through a single genetic defect.
The team recruited members of a prosopagnosia support group and their families into the study, plus Grüter's own relatives. Using a questionnaire to identify prosopagnosia symptoms, the team found 38 prosopagnosics in seven families. By plotting the condition on family trees, the team showed that the inheritance pattern is consistent with the trait being carried by a single gene: just one defective copy of the gene could make the carrier face-blind.
Other people suffer from prosopagnosia due to trauma to the brain that caused brain damage. But for those who have prosopagnosia from birth the open question has been whether the condition is the result of trauma or toxin exposure during early development or inheritance.
The fact that this disorder can be caused by genetic defect demonstrates that at least for one important cognitive ability the brain's structure that supports that ability is coded for genetically. This result then is another piece of evidence against a blank slate view of the brain.
PITTSBURGH--Recognizing faces is effortless for most people, and it's an ability that provides great evolutionary and social advantages. But this ability is impaired in people who have suffered brain damage or in those with a rare congenital condition, and research by Carnegie Mellon University psychologists reveals startling insights into how the brains of those individuals operate. Psychology Professor Marlene Behrmann and postdoctoral associate Galia Avidan have found that people with congenital prosopagnosia--in which their ability to recognize faces is impaired from birth--are not just deficient at recognizing individuals they know, but they are also poor at simply discriminating between two faces when presented side by side. The researchers also have discovered through functional Magnetic Resonance Imaging (fMRI) scans that, contrary to their expectations, the regions of the brain that are activated when normal individuals perceive and recognize faces also are activated in individuals with congenital prosopagnosia (CP). Behrmann and Avidan will summarize the results of their findings in the April issue of the journal Trends in Cognitive Sciences.
Behrmann and Galia said that much remains to be learned from the individuals in their research. They have begun to examine the anatomical details of the brains of their participants, and preliminary findings show that some brain structures are smaller in the region known to control face recognition.
Did Michelangelo or Leonardo Da Vinci have a larger region of their brains for facial recognition? Did they from birth have more neurons dedicated to understanding facial structures? Or were their mental gifts due to more general enhancements of cognitive abilities?
Normally in each cell of a female body one of the two X chromosomes has been deactivated by the placement of methyl groups (a carbon and 3 hydrogens) along the backbone of the DNA double helix. That deactivation is random. Suppose there are two X chromosomes in a woman called A and B where the A chromosome came from her mother and the B chromosome came from her father. In approximately half of the cells the A's will be deactivated and in the other half of the cells the B's will be deactivated. Well, in women who have gay sons the deactivation of the X chromosomes is skewed with one of the X's more often deactivated than the other.
But when Sven Bocklandt of the University of California, Los Angeles, compared blood and saliva samples from 97 mothers of gay men with samples from 103 mothers without gay children he found this process was extremely skewed in the mothers with gay sons, with one X chromosome being far more likely to be inactivated than the other. Only 4% of the mothers without gay sons showed this skewing, compared with 14% of mothers with at least one gay son. Among mothers with two or more gay sons, the figure was 23%.
This result suggests that eventually any woman will be able to have a genetic test done what will predict the odds that one of her sons will be born homosexual.
One can easily imagine all sorts of responses to this. It is safe to say that most women and most men do not want to have homosexual children. The degree of that preference varies and some people do not have a strong preference against their own children being homosexual. There is no doubt even a minority of people who would prefer their children to be homosexual.
So will women who are at greater risk of having homosexual sons become more reticent to have children? Or will they use reproductive technologies such as MicroSort to tip their odds toward having a daughter instead?
One question unanswered by this study is whether the skewing of X chromosome shut-down also increases the odds of lesbianism. The mechanism for producing lesbian female children may be (and I'm guessing is) entirely unrelated to the mechanism for producing homosexual sons. But a follow-up study could easily answer this question by repeating the same analysis with the mothers of lesbian daughters.
Of course, understanding of a genetic mechanism for the development of homosexuality will eventually lead to the development of treatments to alternatively prevent or cause a homosexual outcome. One question I do not have a guess about is whether control over sexual orientation of offspring will produce more or fewer homosexuals. You might argue that since most people either prefer heterosexual children or have no preference (or are at least so politically correct that they won't publically admit to a preference) it is hard to see how control over sexual orientation could increase the number of homosexuals. But there is one big point to consider: It takes only a small fraction of the population to choose having a homosexual child to increase the number that are born. Suppose that only 3% of male births are homosexual. It would take only 1 in 20 women (or gay men who hire a surrogate woman to carry a baby) deciding they'd rather have homosexual son to increase the number born.
My guess is that there is a greater chance that control of reproduction could increase the number of lesbians. After all, it is women who carry the babies, not men. Will most lesbian women want to have heterosexual or homosexual daughters? Anyone have a reason to think they know the answer?
This question of preferences for offspring sexual orientation is part of what I consider to be a huge coming issue: when people can control more characteristics of their offspring what choices will they make? Some choices are not hard to guess. People will want their kids to be smarter and better looking. But what will be the chosen frequency of, say, blondness or introversion versus extroversion? Or height? Tall overall is my guess. But how much taller? Will the distribution of heights become narrower since people won't want to burden their kids with excessive height? (that is my guess). Will personality choices for offspring become problematic for society as a whole? See my posts Altruistic Punishment And Genetic Engineering Of The Mind and Brain Rewards For Carrying Out Altruistic Punishment for more on that question.
A variant in the GRM3 glutamate receptor gene may increase the risk for schizophrenia while simultaneously lowering cognitive ability.
Glutamate is a key neurotransmitter long thought to play a role in schizophrenia. The gene identified in this study makes the glutamate receptor (GRM3) which is responsible for regulating glutamate in synapses — spaces in between brain cells — where chemicals like glutamate transfer information from cell to cell. The amount of glutamate remaining in the synapse may have a downstream impact on cognition.
GRM3 alters glutamate transmission, brain physiology and cognition, increasing the risk for schizophrenia. To pinpoint the section of the gene responsible for these changes, scientists are exploring a region where the gene may differ by one letter at a location called SNP4. The normal variation is spelled with either an 'A' — the more common of the two — or a 'G'. Patients with schizophrenia are more likely to inherit an 'A' from either parent, indicating the 'A' variant slightly increases risk. The 'A' variant is also associated with the pattern of traits linked with the disorder. This was true in patients, their healthy siblings, and normal volunteers.
In the study, people with an 'A' variant have differences in measures of brain glutamate. In a postmortem study of brain tissue, the 'A' variant was associated with lower levels of the chemical that promotes gene expression for the protein responsible for regulating the level of glutamate in the cell. N-acetylaspartate, a measure of cell health evaluated through the use of MRI spectroscopy, was lower in 'A' participants. 'A' carriers had poorer performance on several cognitive tests of prefrontal and hippocampal function than people with the 'G' variant. The 'G' marker was associated with relatively more 'efficient' processing in the prefrontal cortex. Those who inherit the 'G' variant scored higher on verbal and cognitive tests than those who have two of the 'A' variant. Scientists think the less common 'G' variant may exert a protective effect against the disease.
People with schizophrenia and their healthy siblings share the inefficient brain physiology, and cognition patterns, which suggests a link to genetic risk, though the disease itself is most likely caused by a combination of genetic and environmental factors. The gene seems to affect the mechanism of memory encoding only as there was no genotype effect seen during retrieval in the memory tests.
What I find more interesting than the link to schizophrenia risk is that these two genetic variants differ in their impact on normal cognitive function. GRM3 SNP4 looks like it will turn out to be one of the locations in the human genome which have variations that produce different levels of intelligence. In the next 10 years expect to see the identification of dozens and perhaps even hundreds more of additional locations of genetic variants that influence intellectual abilities and personality. Declining costs of DNA testing will drive the rate of such discoveries up by orders of magnitude.
MADISON - For children growing up poor, money isn't the only solution to overcoming the challenges of poverty.
According to a new study, the genes and warm support received from parents also can buffer these children against many of the cognitive and behavioral problems for which poverty puts them at risk. The findings are published in the May issue of the journal Child Development.
Numerous studies show that economic hardship during childhood elevates a person's risk of developing conduct problems and lower intelligence, says Julia Kim-Cohen, co-author of the recent paper and postdoctoral fellow in psychology at the University of Wisconsin-Madison and the Institute of Psychiatry at King's College London.
But, as she notes, some children overcome these odds and, in fact, perform better on intelligence or behavioral tests than would be expected, given the level of poverty in which they're raised. These children, says Kim-Cohen, are considered to be "resilient" - or capable of doing well despite adversity.
Interested in understanding the factors that contribute to a child's resilience to poverty, Kim-Cohen and her colleagues studied genetic and environmental differences among 1,116 mothers and their five-year-old same-sex twins, part of the E-Risk longitudinal study being conducted in England and Wales.
"Children in our study experienced more than just poverty, as measured by family income level," explains Kim-Cohen, adding that often their parents were poorly educated, owned no car and held menial jobs or no job at all. "Living in the poorest neighborhoods, their homes were rated as being overcrowded, damp or in disrepair," she says.
Comparisons of identical and fraternal twins show that there is a strong genetic component to how people respond to lousy childhood environments.
After determining the economic conditions of each family, the researchers conducted interviews and tests to evaluate the mother's warmth and support toward her children, as well as the children's temperament and intelligence. The children who performed better than expected on behavioral and cognitive tasks, says Kim-Cohen, are the ones more resilient to the poor conditions in which they were raised.
To determine the role of genes in buffering children against poverty, the researchers studied differences among the twins, some who were identical (sharing all genes) and others who were fraternal (sharing half their genes). If identical twins have levels of resilience similar to each other, compared to that between fraternal twins, Kim-Cohen says it would be due, in part, to genetics.
"Genetic endowment is known to influence a variety of children's capabilities, such as how well they use language, how quickly they learn new skills, and how outgoing and cheerful they are," says co-author Terrie Moffitt, a psychology professor at UW-Madison and King's College London. Given these genetically influenced capabilities, Moffitt adds, "We reasoned that they might help poor children in their struggle to overcome their lack of economic advantages."
Results from the study show that genetic makeup does play a part in resilience. According to the statistical analysis, genes explained 70 percent of the variability in children's behavioral resilience and 46 percent of the difference in their cognitive ability.
"This means that when the children in a classroom or neighborhood differ on behavior problems or cognitive achievement," explains Moffitt, "about half of that variation across the group emerges from the fact that every child has his or her own individual genetic endowment."
What is interesting here is that the effect was stronger for behavior resilience than for cognitive ability. This is not surprising. My guess is that achieved level of cognitive ability is less affected by social environment than is personality because personality adjustment in development provides ways to adapt to the kinds of social conditions developing children found themselves in. Think of the resilience as a product of both genetic variations for cognitive ability (which affect the basic capacity to develop strategies to deal with others) and genetic variations for personaliy that affect behavior more directly. There is at least one known gene which comes in variations that make one more or less susceptible to becoming anti-social as a result of mistreatment when young. Terrie Moffitt, one of the participants in this latest study, previously participated in an analysis of twins from the longitudinal Dunedin Multidisciplinary Health and Development Study which found that Mono Amine Oxidase A (MAOA) variants affected whether mistreatment will produce violent personalities. I've previously reported on this work.
It would be very helpful to know whether the children that are behaviorally more resilient reproduce more or less than children or who are less behaviorally resilient. Is natural selection in industrialized countries currently selecting for or against people who behave well? From the standpoint of cogntive ability there are indications that genes for higher cogntive ability are being selected against. For instance, an Australian Twin Registry study found that those who reach a higher level of educational achievement have fewer children and that this scales across a large range of levels of educational achievement. So pushing smart people to go on to college and graduate school may be providing society a short term benefit of higher skilled workers at the expense of having a dumber future population.
Researchers at Mount Sinai School of Medicine are first to strongly link a specific gene with autism. While earlier studies have found rare genetic mutations in single families, a study published in the April issue of the American Journal of Psychiatry is the first to identify a gene that increases susceptibility to autism in a broad population.
Approximately 1 in 1,000 people have autism or autistic disorder. It appears to be the most highly genetic of all psychiatric disorders. If a family with one autistic child has another child the chance that this child would be autistic is 50 to 100 times more likely to than would be expected by chance. However, it's clear that no single gene produces the disorder. Rather, the commonly accepted model states that it is a result of the accumulation of between five to ten genetic mutations.
"Identifying all or most of the genes involved will lead to new diagnostic tools and new approaches to treatment," said Joseph Buxbaum, PhD, Associate Professor of Psychiatry, Mount Sinai School of Medicine and lead author of the study.
Several studies have implicated a region on chromosome 2 as likely to be involved in autism. An earlier study by Dr. Buxbaum and his colleagues narrowed the target to a specific region on this chromosome. He and his colleagues conducted a systematic screening of this region in 411 families that have members with autism or autistic disorder. The families were recruited through The Seaver Autism Research Center at Mount Sinai School of Medicine and the Autism Genetic Resource Exchange.
They found genetic variations in one gene that occur with greater frequency in individuals with autism disease and their family members. This gene codes for a protein that is involved in production of ATP, the molecule that acts as fuel providing the energy cells need to function. The mutations identified lead to production of excessive amounts of this protein. Dysfunction of this gene could lead to irregularities in the production of molecules that fuel the cells. Since brain cells consume large amounts of energy even minor disruptions in production of such fuel can significantly affect the cells ability to function normally.
The abstract of the paper identifies the gene as Mitochondrial Aspartate/Glutamate Carrier SLC25A12.
Why don't we already know all the genes that contribute to autism? It costs too much to do genetic sequencing. If the cost of DNA sequencing was about 3 orders of magnitude lower then the entire genomes of tens of thousands of autistic and non-autistic people could be sequenced and we'd find out very quickly which genetic variations contribute to autism and to most other diseases as well.
Since the costs of DNA sequencing and of testing individual DNA letters (Single Nucleotide Polymorphisms or SNPs) continues to drop and since it is reasonable to expect the costs to drop by two or three orders of magnitude within the next 10 years I expect all the genetic variations that contribute to autism, Alzheimer's, Parkinson's and most other neurological diseases to be known by 2015. The rate of discovery of contributing genetic variations will rise by orders of magnitude as the costs drop by orders of magnitude.
Some people claim that there is no evidence that natural selection has caused differences in different human populations in the frequency of genetic variations that create differences in cognitive performance. However, a recent combination of reports about a single gene which affects cognitive function provides such evidence. Recent research reports on the effects that variations of the prion protein gene (PRNP) have on cognitive ability, other reports that PRNP variations affect the risk for getting prion diseases such as kuru and Creutzfeld Jacob Disease (CJD), and still other reports on the distribution of the PRNP gene variations in different human populations suggest that in different ecological niches natural selection has indeed operated to produce differences in human cognitive function.
For a specific example of a genetically caused difference in cognitive ability in different human populations that has been caused by natural selection first see my previous post Prion Gene Influences Cognitive Ability which reported on how the M129V variations in the prion protein gene (PRNP) may cause differences in cognitive ability between those who and those who do not have that variation. Here's an excerpt from the abstract of a research paper on PRNP genetic variations and cognitve function.
We have recently shown that methionine at codon 129 in the prion protein is associated with white matter reduction in a group of healthy volunteers and schizophrenic patients. The present study examines the influence of the same genetic variation on psychometric cognitive performance measurements in 335 community-based healthy volunteers. The polymorphism was associated with Full Scale IQ (genotype: F=4.38, df=2/317, P=0.013; allele: F=8.04, df=1/658, P=0.005), as measured by HAWIE-R (German version of the Wechsler Adult Intelligence Scale, Revised). Genotype accounted for 2.7% of the total variability in Full Scale IQ (partial eta2=0.027).
Why is this interesting in terms of natural selection for cognitive performance in different human environments? We know that the M129V variation occurs at different frequencies in different in populations. In fact, cannibalism have have selected for the heterozygous occurrence of M129V variations in cannibals in Papua New Guinea.
From approximately 1920 to 1950, a kuru epidemic devastated the Fore in the Highlands of Papua New Guinea. At mortuary feasts, kinship groups would consume deceased relatives, a practice that probably started around the end of the 19th Century, according to local oral history. The Australian authorities imposed a ban on cannibalism there in the mid-1950s.
The same genetic variation in the prion protein that helps protect against Creutzfeld Jacob disease turned out to do the same for kuru. Studying Fore women who had participated in mortuary feasts, Collinge's group found that 23 out of the 30 women were heterozygous for the prion protein gene, possessing one normal copy and one with the M129V mutation.
The researchers sequenced and analyzed the prion protein gene in more than 2000 chromosome samples from people selected to represent worldwide genetic diversity. They found either M129V or E219K in every population, with the prevalence decreasing in East Asia (except for the Fore, who have the highest frequency in the world).
Collinge's team also studied the diversity of sequence variations in a block of DNA containing the prion protein gene, in European, African, Japanese, and Fore populations. The prevalence of the M129V and E219K variations, even when the sequence at other spots was highly variable, indicated that the variations were ancient--more than 500,000 years old, according to authors' estimates.
Finally, the researchers identified a telltale signature of balancing selection in the gene: a greater than average number of highly variable sites, and a smaller than average number of low-frequency variations.
These findings are consistent with other lines of evidence indicating that prehistoric populations practiced cannibalism, such as cuts and burn marks on Neanderthal bones, and biochemical analysis of fossilized human feces.
M129V allele frequencies do not differ only among populations which were recently cannibals as compared to populations that were not recently cannibals. For instance, allele frequencies for M129V are different in Turkey than in most of Europe and East Asia.
Three known polymorphisms but no other gene variants were detected in the PRNP coding sequence of the Turkish individuals. Genotype frequencies at codon 129 were 57% Met/Met, 34% Met/Val and 9% Val/Val, with an allele frequency of 0.740:0.260 Met:Val. These distributions are considerably different from those reported for other normal populations residing in Western Europe and East Asia, except in Crete. The higher frequency of 129 Met-homozygotes in Turkey than in Western Europe suggests that the Turkish are at greater risk of developing CJD.
If the research work which shows that M129V reduces brain volume and reduces intelligence is confirmed upon further investigation then this will be an example of a difference in selective pressures in different environments causing differences in frequencies of alleles that affect cognitive function.
The researchers, led by Howard Hughes Medical Institute (HHMI) investigator Bruce Lahn at the University of Chicago, reported their findings in an advance access article published on January 13, 2004, in the journal Human Molecular Genetics. Patrick Evans and Jeffrey Anderson in Lahn's laboratory were joint lead authors of the article.
“People have studied the evolution of the brain for a long time, but they have traditionally focused on the comparative anatomy and physiology of brain evolution,” said Lahn. “I would venture, however, that there really hasn't been any convincing evidence until now of any gene whose changes might have contributed to the evolution of the brain.”
In this study, the researchers focused on a gene called the Abnormal Spindle-Like Microcephaly Associated (ASPM) gene. Loss of function of the ASPM gene is linked to human microcephaly - a severe reduction in the size of the cerebral cortex, the part of the brain responsible for planning, abstract reasoning and other higher brain function. The discovery of this association by HHMI investigator Christopher A. Walsh and colleagues at Beth Israel Deaconess Medical Center is what prompted Lahn to launch an evolutionary study of the gene.
Lahn and his colleagues compared the sequence of the human ASPM gene to that from six other primate species shown genetically to represent key positions in the evolutionary hierarchy leading to Homo sapiens. Those species were chimpanzee, gorilla, orangutan, gibbon, macaque and owl monkey.
“We chose these species because they were progressively more closely related to humans,” said Lahn. “For example, the closest relatives to humans are chimpanzees, the next closest are gorillas, and the rest go down the ladder to the most primitive.”
For each species, the researchers identified changes in the ASPM gene that altered the structure of the resulting protein, as well as those that did not affect protein structure. Only those genetic changes that alter protein structure are likely to be subject to evolutionary pressure, Lahn said. Changes in the gene that do not alter the protein indicate the overall mutation rate - the background of random mutations from which evolutionary changes arise. Thus, the ratio of the two types of changes gives a measure of the evolution of the gene under the pressure of natural selection.
Lahn and his colleagues found that the ASPM gene showed clear evidence of changes accelerated by evolutionary pressure in the lineage leading to humans, and the acceleration is most prominent in recent human evolution after humans parted way from chimpanzees.
“In our work, we have looked at evolution of a large number of genes, and in the vast number of cases, we see only weak signatures of adaptive changes,” said Lahn. “So, I was quite surprised to see that this one gene shows such strong and unambiguous signatures of adaptive evolution — more so than most other genes we've studied.”
By contrast, the researchers' analyses of the ASPM gene in the more primitive monkeys and in cows, sheep, cats, dogs, mice and rats, showed no accelerated evolutionary change. “The fact that we see this accelerated evolution of ASPM specifically in the primate lineage leading to humans, and not in these other mammals, makes a good case that the human lineage is special,” said Lahn.
According to Lahn, among the next steps in his research will be to understand how ASPM functions in the brain. Studies by Walsh and others hint that the protein produced by the gene might regulate the number of neurons produced by cell division in the cerebral cortex. Lahn and his colleagues plan functional comparisons of the ASPM protein among different species, to understand how this gene's function or regulation changes with evolution.
The acceleration of ASPM functional changes in the whole lineage this suggests that there was evolutionary selective pressure for changes in cognitive function not just from the point where humans split off from chimpanzees but even much early as well. Was that pressure consistent and continuing? Or did it happen periodically? One can only speculate at this point. Perhaps something about the shape of a primate makes higher intelligence more useful. If so then the more that shape changes in certain directions the more the selective pressure increases. That could come as a result of the types of habitats primates moved into or how they functioned in those habitats or from what they used as food sources or still other factors. There are a lot of possibilities.
One thing interesting about intelligence as an adaptive mutation is that it allows an animal to learn how to adapt itself to new environments. An animal that is in exactly the same environment that its ancestors evolved in might be able to do well in that environment just by following instincts. But in a new environment a species has to either get mutated into a new shape that better adapts the species to the environment or it has to learn how to function in that environment without changing shape. Look at human clothing. A species with fur that migrates into a colder environment might simply gradually develop metabolic changes for cold weather and fur thickness changes that adapt that species to the colder environment. Humans whose ancestors lived in colder environments do have genetic variations in their mitochondria that allow them to be warmer in cold weather. But humans also were smart enough to develop the ability to kill furry animals and use their pelts for clothing to be warmer. So humans could use their intelligence to adapt themselves to cold climates more rapidly than specific mutational changes would happen to help in the adaptation. Humans spread out across all the continents and adapted themselves to a very wide range of environments even before the modern age of science and technology. What will be interesting to find out is whether specific types of ancient environments required greater cognitive abilities and, if so, what was it about those environments that levelled greater demands on the brain.
You might be wondering how exactly scientists can detect selective pressure on a gene. Note how the article talks about mutations that are not functionally significant versus mutations that are functionally significant. Well, compare two related species for the ratio of functionally significant to functionally insignificant variations in the same gene. The higher the ratio the higher the selective pressure must have been.
Here's an intuitive example of why ratios of functionally signficant to functionally insignificant mutations reveal the extent of past selective pressure: Suppose at some point in the past there was a species that has only a million animals of that species. Suppose they had some gene we will call X. Suppose they all had only functionally insignificant mutations in X and that between the million animals of that species they had 20 different combinations of mutations in X. Then suppose a single animal in that species was born that had a mutation in X that caused a functional change that made that animal more adaptive. Perhaps the mutation in X made the animal smarter and therefore more successful in finding food. Well, that animal with the "smart X" variation also had one of the existing 20 combinations of functionally insignificant mutations. The other 19 combinations existed only in animals that did not have the "smart X" intelligence-enhancing mutation. All the other animals of that species will therefore be less successful, on average, at reproducing. That will, over a period of generations, cause those other 19 combinations in the X gene to become far less common. Many of the combinations in X likely will disappear entirely as their carriers become outcompeted in the search for food and fail to reproduce successfully. The 1 combination of insignificant variations that occurs with the "smart X" mutation will become far more common and may become the only combination of insignificant variations in the X gene until new insignificant combinations start accumulating across generations as new mutations happen in animals that have the "smart X" mutation.
The point is that a valuable mutation will mprove the relative reproductive success of the first animal that gets it. But then any unimportant or less important mutations that animal also has will be propagated along with the important mutation. The amount of overall variation in that gene will go down in future generations as the animals that do not have the valuable mutation but which have various functionally insignificant mutations do not reproduce as successfully. Valuable mutations have the effect of reducing the number of functionally unimportant mutational variations that will be found around genes that has the valuable mutations.
Update: Nicholas Wade of the New York Times has more details about the historical frequency of ASPM mutations.
"There has been a sweep every 300,000 to 400,000 years, with the last sweep occurring between 200,000 and 500,000 years ago," Dr. Lahn said, referring to a genetic change so advantageous that it sweeps through a population, endowing everyone with the same improved version of a gene.
By this measure humans may be due for another ASPM mutation. Perhaps there is some human out there walking around with the next intelligence-enhancing ASPM mutation.
Where Lahn talks about a mutation that "sweeps through a population" understand what that really means: All animals that did not have the mutation in a given species were outcompeted and, over some generations, failed to reproduce. The mutation didn't just jump from one ape to another ape like a viral infection. The line of successive mutations were each so helpful for enhancing survival and reproduction that animals that didn't have them were outcompeted for food or for mates or in fights and perhaps in all of those ways.
Wade says at least 5 other genes cause microcephaly but they have not yet been identified. Once they are expect evolutionary geneticists to repeat the same comparison between species as was done with ASPM. While few humans appear to have functional variations in ASPM (aside from victims of microcephaly) it is possible that some of these yet-to-be-discovered genes will turn out to vary between humans. Humans do vary in brain size and brain shape. Genetic variations in some genes must be causing this. Though some of those variations might be occurring in genes that are not responsible for microcephaly.
In a report in Molecular Psychiatry entitled "M129V variation in the prion protein may influence cognitive performance" German scientists Dan Rujescu, Annette Hartmann, Claudia Gonnermann, Hans-Jürgen Möller, and Ina Giegling of Ludwig-Maximilians-University, in Munich, Germany report that the gene for prion protein has genetic variations that influence cognitive ability.
Cognitive abilities are influenced by an interplay of genes and environment. With regard to the genetic component, multiple genes are assumed to be responsible for interindividual variation in cognitive abilities. Despite tremulous progress in molecular genetics, little is known about specific genes that contribute to this complex behavior. In an attempt to further delineate the genetic component of cognitive abilities, the authors investigated the relationship between a genetic variation in the prion protein and variations in cognitive abilities in 335 healthy volunteers. The main result is that a common variation in the prion protein gene is associated with cognitive abilities in our sample of healthy volunteers. These findings are further strengthened by the observation that the effect occurs in a gene dose dependent manner. The effect of this variation accounted for 2.7% of the total variability in cognitive abilities, further strengthening the assumption that many genetic variations with only a small effect influence human cognitive abilities. The mechanisms by which the prion protein might actually act on cognitive performance are unclear, but several lines of evidence suggest that this protein is involved in neuroprotection. To the authors' knowledge, this is one of the first reports on the influence of a common genetic variation on individual differences of cognitive abilities in healthy individuals. Nevertheless, it should be emphasized, that replications of our findings are needed before firm conclusions can be drawn.
Researchers on cognitive ability believe a large number of sites in the genome have genetic variations that influence cognitive abilities. In one of his books brain genetics researcher Robert Plomin says the same holds true for personality types. So it will take a large number of reports such as the one above to identify all the genetic variations that cause intelligence and personality differences.
OTTAWA, Oct 17, 2003 (Canada NewsWire via COMTEX) -- After a pioneering seven-year study, Canadian scientists have discovered a new genetic difference in people suffering from severe depression and in those who have committed suicide. The findings by collaborative researchers at the University of Ottawa and the Institute of Mental Health Research, and McGill University's Douglas Hospital, Montreal -- represent a significant step forward in identifying individuals at risk for debilitating depression or even death.
The study - "Impaired repression at a 5-hydroxytryptamine -1A receptor gene polymorphism associated with major depression and suicide", published in a recent issue of the Journal of Neuroscience, showed the same genetic difference or 'single nucleotide polymorphism (SNP)' in a gene that contributes to the serotonin system which regulates mood cycles in human beings. This SNP in the serotonin-1A gene was two-fold enriched in people with depression, and four-fold enriched in those who had completed suicide, as compared to normal control groups.
The studies showed for the first time that the polymorphism of the serotonin-1A gene impacts by inhibiting the function of a protein called NUDR, leading to abnormal levels of serotonin-1A gene expression and decreased serotonin, and a key factor in the incidence of depression.
The researchers found a mutation in the gene encoding for the receptor, a protein that transmits brain signals, which more than doubles the risk of suicidal behaviour in those who carry it.
An analysis of the DNA showed 41% of the suicidal patients had the 5-HT2A receptor mutation, compared with 24% of the non-suicidal patients and 18% of the healthy subjects.
A genetic variability might also explain why suicide rates vary strongly between populations with different ethnic origins. For example, the annual suicide rate in Finland (for males) is 43 per 100,000 people, one of the highest rates in the world.
But the rate for neighbouring Norway is only 21 per 100,000, less than half.
"It may be interesting to look into the distribution of the [mutation] in these countries," said Dr. Hrdina.
As the costs of DNA Single Nucleotide Polymorphism (SNP) testing of single letter differences (a.k.a. alleles) in DNA sequences become cheaper the distributions of various alleles that affect mental state and behavior will become better known. Populations at greater risk for assorted mental illnesses and behavioral problems will have their problems traced down to a genetic level.
Whether it will be possible to develop compounds to target the various alleles that cause mental problems remains to be seen. Certainly pharmaceutical companies will try. My guess is that the answer will be "Yes" for some but not all. An allele that causes overexpression, for instance, may simply have no easy way for a compound to be designed that can reach all the way into the nucleus and selectively bind somewhere to repress it. The level of specificity needed may be beyond what a conventional drug can achieve. Also, for more rare alleles the market may not be big enough for a drug company to spend hundreds of milions on development. If you are going to have a major mental problem caused by a genetic variation best to have a variation that is fairly common in industrialized countries.
Aside: I think the above article misspells the receptor abbreviation. The journal abstract below for the original paper spells it slightly differently.
From the abstract of the published paper Impaired Repression at a 5-Hydroxytryptamine 1A Receptor Gene Polymorphism Associated with Major Depression and Suicide in the Journal of Neuroscience:
Our data indicate that NUDR is a repressor of the 5-HT1A receptor in raphe cells the function of which is abrogated by a promoter polymorphism. We suggest a novel transcriptional model in which the G(-1019) allele derepresses 5-HT1A autoreceptor expression to reduce serotonergic neurotransmission, predisposing to depression and suicide.
The discovery could lead to the development of genetic tests to identify those at risk. But it also poses questions about the ramifications of such testing. During their 10-year study investigating the causes of suicide, the Canadian team discovered a genetic variation that affects brain chemistry. They found that depressed individuals with a mutation in the gene encoding the serotonin 5-HT2A receptor are more than twice as likely to attempt suicide as those who suffered from depression but did not carry the mutation, says Pavel Hrdina, a neurobiologist at the Royal Ottawa Hospital and study co-author. Serotonin is a neurotransmitter that carries messages between brain cells and is thought to be involved in the regulation of emotion, among other functions. For some years, scientists have suspected that the genes regulating the serotonin system could be one of the culprits.
GAD2, which sits on chromosome 10, acts by speeding up production of a neurotransmitter in the brain called GABA, or gamma-amino butyric acid. When GABA interacts with another molecule named neuropeptide Y in a specific area of the brain - the paraventricular nucleus of the hypothalamus - we are stimulated to eat.
The researchers behind this study believe that people who carry a more active form of the GAD2 gene build up a larger than normal quantity of GABA in the hypothalamus, and suggest that this over accumulation of GABA drives the stimulus to eat further than normal, and is thus a basis for explaining why obese people overeat.
Professor Philippe Froguel, senior author of the research, from Imperial College London, and Hammersmith Hospital, London, and who carried out the research while at the Institut Pasteur de Lille, France, said: "The discovery that this one gene plays a role in determining whether someone is likely to overeat could be crucial in understanding the continued rise in obesity rates around the world.
"Genetic factors alone can not explain the rapid rise in obesity rates, but they may provide clues to preventative and therapeutic approaches that will ease the health burden associated with obesity.
"Having identified this gene, it may be possible to develop a screening programme to identify those who may be at risk of becoming obese later in life, and take effective preventative measures."
The team compared genome-wide scans of 576 obese and 646 normal weight adults in France, from which they identified two alternative forms, or alleles, of the GAD2 gene.
One form of the gene was found to be protective against obesity, while another increased the risk of obesity. The normal weight group of French adults had a higher frequency of the protective form of the GAD2 gene. Obesity is three to five times less prevalent in France than in the USA.
The discovery, which will be published in an upcoming issue of the journal Public Library of Science (http://www.plos.org), involves researchers originally from Sweden and France who collaborated at the University of Washington in Seattle.
The gene, on Chromosome 10, was first connected to diabetes in 1991 by Dr. Åke Lernmark, R. H. Williams Professor of Medicine and adjunct professor of immunology at the UW. The GAD2 gene is responsible for the protein GAD65, which plays a role in the healthy use of insulin by the body. Lernmark is a native of Sweden, which has one of the highest rates of Type I diabetes incidence in the world.
If this result is confirmed in other populations expect GAD2 expression and the activity of the GAD6 protein to become targets for drug development.
US and Japanese researchers have discovered a rare serotonin transporter gene mutation causes some cases of obsessive compulsive disorder. (same article here)
Analysis of DNA samples from patients with obsessive compulsive disorder (OCD) and related illnesses suggests that these neuropsychiatric disorders affecting mood and behavior are associated with an uncommon mutant, malfunctioning gene that leads to faulty transporter function and regulation. Norio Ozaki, M.D., Ph.D., and colleagues in the collaborative study explain their findings in the October 23 Molecular Psychiatry.
Researchers funded by the National Institutes of Health have found a mutation in the human serotonin transporter gene, hSERT, in unrelated families with OCD. A second variant in the same gene of some patients with this mutation suggests a genetic “double hit,” resulting in greater biochemical effects and more severe symptoms. Among the 10 leading causes of disability worldwide, OCD is a mental illness characterized by repetitive unwanted thoughts and behaviors that impair daily life.
“In all of molecular medicine, there are few known instances where two variants within one gene have been found to alter the expression and regulation of the gene in a way that appears associated with symptoms of a disorder,” said co-author Dennis Murphy, M.D., National Institute of Mental Health (NIMH) Laboratory of Clinical Science. “This step forward gives us a glimpse of the complications ahead in studying the genetic complexity of neuropsychiatric disorders.”
These mutations do not appear to be the causes of most cases of OCD.
Psychiatric interviews of the patients’ families revealed that 6 of the 7 individuals with the mutation had OCD or OC personality disorder and some also had anorexia nervosa (AN), Asperger’s syndrome (AS), social phobia, tic disorder, and alcohol or other substance abuse/dependence. Researchers found an unusual cluster of OCD, AN, and AS/autism, disorders together with the mutation in approximately one percent of individuals with OCD.
The scientists analyzed DNA from 170 unrelated individuals, including 30 patients each with OCD, eating disorders, and seasonal affective disorder, plus 80 healthy control subjects. They detected gene variants by scanning the hSERT gene’s coding sequence. A substitution of Val425 for Ile425 in the sequence occurred in two patients with OCD and their families, but not in additional patients or controls. Although rare, with the I425V mutation found in two unrelated families, the researchers propose it is likely to exist in other families with OCD and related disorders.
Having the pair of mutations appears to make symptoms worse.
In addition to the I425V mutation, the two original subjects and their two siblings had a particular form of another hSERT variant, two long alleles of the 5-HTTLPR polymorphism. This variant, associated with increased expression and function of the serotonin transporter, suggests a “double hit,” or two changes within the same gene. The combination of these changes, both of which increase serotonin transport by themselves, may explain the unusual severity and treatment resistence of the illnesses in the subjects and their siblings.
“This is a new model for neuropsychiatric genetics, the concept of two or maybe more within-gene modifications being important in each affected individual. This is also probably the first report of a modification in a transporter gene resulting in a gain rather than a decrease in function,” said NIMH Director Thomas Insel, M.D.
SERT allows neurons, platelets, and other cells to accumulate the chemical neurotransmitter serotonin, which affects emotions and drives. Neurons communicate by using chemical messages like serotonin between cells. The transporter protein, by recycling serotonin, regulates its concentration in a gap, or synapse, and thus its effects on a receiving neuron’s receptor.
Transporters are important sites for agents that treat psychiatric disorders. Drugs that reduce the binding of serotonin to transporters (selective serotonin reuptake inhibitors, or SSRIs) treat mental disorders effectively. About half of patients with OCD are treated with SSRIs, but those with the hSERT gene defect do not seem to respond to them, according to the study.
People who have more rare mutations have a tougher time finding effective treatments for the obvious reason that they make up a smaller market for any potential drug development. However, the ability to test for rarer mutations opens up the possibility of identifying subcategories of sufferers of a particular disorder to test them with a wider range of existing drugs than would normally be used on people for whom effective treatments are already known.
Also see the previous post Stanford Researchers Discover Treatment For Obsessive Shopping Disorder.
About nine per cent of people have at least one copy of a gene for 5HT2a that call for the amino acid tyramine at one point in the receptor protein. The rest call for histamine. People with the tyramine variant make receptors that are less readily stimulated by serotonin.
De Quervain's team compared 70 people with the tyramine form to 279 with the histamine form. The tyramine group was 21 per cent worse at remembering a list of five words or simple shapes five minutes after seeing them.
There is going to be a veritable torrent of additional such discoveries in the next 10 or so years. Lots of genetic variations that contribute to intelligence will be identified. The identification of these variations will be useful for breeding decisions and offspring genetic engineering. The use of the term "breeding decisions" may seem cold but depending on how quickly offspring genetic engineering becomes available a great many people may make decisions about mating for reproduction based on the genetic profiles of potential mates. If many genetic variations that contribute to cognitive differences are identified in many years before offspring genetic engineering becomes possible then people will opt to choose their mates based on what genetic contributions their prospective mates can make to the cognitive ability of their offspring.
Some of the variations that raise and lower intelligence will turn out to do so by changing levels of expression of genes. Attempts will be made to develop drugs that will bind at targets in the regulatory chains that control the expression of those genes in order to make those genes express in less mentally capable people in ways that mirror their expression levels in smarter people. Also, attempts will be made to develop drugs that bind to receptors and change their shapes to be more like the shapes found in smarter people. The bottom line is that many of the genetic variations that contribute to cognitive ability will provide targets for pharmaceutical development. Every such discovery is another potential target for drug development.
It was already known that some anti-depressants that work on the 5HTa gene's receptor product and that those drugs have the side effect of interfering with short term memory. Another recent published report found that there is also a genetic variation in 5HT2a that appears to impact whether anti-depressant Paroxetine (a.k.a. Paxil) causes intolerable side effects in patients.
One variation of the 5HT2a gene, based on a single nucleotide change in the DNA sequence, is thought to affect the amount of the receptor on nerve cells. When the researchers compared the version of this gene that a patient had to his or her experience taking the drug, the differences due to gene variation were striking. People with the one version of the gene were much more likely to discontinue therapy due to intolerable side effects when compared to the two other versions (46 percent vs. 16 percent).
Unfortunately the press release for the second report doesn't state whether the same nucleotide is involved as in the first case.
Researcher Robert Plomin has found from a study of twins in Britain that genes which have variations which cause learning disabilities also have variations that are responsible for causing differences in normal variations in intelligence.
Research from the largest study of twins ever conducted in the UK shows that genetic influences on common learning disabilities are not specific to each disorder.
Professor Robert Plomin of the Institute of Psychiatry, King’s College London today presents evidence on common learning disabilities to the BA Festival of Science at the University of Salford, Greater Manchester.
The Twins Early Development Study (TEDS) compares identical and non-identical twins born in England in 1994-6 and latest findings are from year-long assessments by teachers of reading and maths at age seven.
Researchers found three main reasons that genes involved in common learning disabilities are generalists in three ways. First, genes that affect these disabilities are the same genes responsible for normal variation in learning abilities. Second, genes are not specific to one aspect of a learning disability but are general to many aspects of the disorder. Thirdly, genes affecting one learning disability also affect others.
Professor Plomin says: ‘Although simple genetic anomalies can lead to specific syndromes, most common problems such as language and reading problems are caused by a range of genetic and environmental risk factors. Many of these causal factors overlap in their effects on different disorders.’
What does this mean? Many learning disabilities may simply be the result of inheriting too many intelligence lowering variations of different genes that contribute to determining mental abilities.
The study also shows that genes that affect common learning disabilities are also responsible for normal variation in learning abilities."The abnormal is normal - what we call abnormal is merely the low end of the same genetic and environmental factors responsible for normal variation."
"We found the same genes responsible for ability and disability," he said. "In one sense abnormal is normal. There are no disabilities, just distributions of genes."
This result supports the argument that the general measure of intelligence known as 'g' has a biological foundation. Many of the genes that affect intellectual ability affect ability throughout the brain.
"There is a general set of genes that operates in the brain to affect all learning processes," he said.
People with short versions of the serotonin transporter gene are more prone to binge drinking and anxiety. (bold emphasis added)
NIAAA clinical investigators Paolo B. DePetrillo, M.D., and Research Fellow Aryeh I. Herman B.A., along with researchers from George Washington University in Washington, D.C., conducted the study of 262 male and female college students and analyzed data from the largest homogenous group: 204 male and female Caucasian college students aged 17 to 23 years. To assess the frequency and patterns of alcohol consumption, the scientists asked all the students a set of questions, for example, how many times in the past two weeks they had engaged in binge drinking (five or more drinks for men and four or more drinks for women on one occasion).
The research team also analyzed each student's genotype with a focus on the 5-HTT gene, which is involved in recycling the chemical serotonin after it is secreted into the synapse of a cell. The researchers determined which students had long or short versions of this so-called serotonin transporter gene.
Everyone inherits two copies of each gene, one from each parent. There are two normal variations, or polymorphisms, of the serotonin transporter gene, labeled the long and the short variants. Most people are heterozygous, that is, they have one copy of each variant, but about 30 percent of the Caucasian population are homozygous (carry duplicate copies) of either the long or the short version. This percentage varies depending on the ethnic background of the individual.
The researchers found that the students who carried two copies of the short version of 5-HTT were more likely to report troublesome drinking patterns. Dr. DePetrillo says, "Our findings reveal a significant association of the serotonin transporter promoter polymorphism with increased alcohol consumption behavior in the students that we studied. Taken together with other research, this finding suggests that genetically mediated differences in serotonergic response play an important role in mediating patterns of alcohol intake." The students with two copies of the short form of the gene engaged more frequently in binge drinking, drank more often to get drunk, and consumed more alcoholic drinks per occasion than did students with the other genotypes.
Another difference the researchers observed was that students with at least one copy of the long variant of the 5-HTT gene tended to consume a smaller number of drinks at a sitting, even though they went out to drink as often as the other students.
Why should the presence of the shorter gene variant make such a difference? The authors speculate that, because individuals who are homozygous for the short version are known to be at risk for higher levels of anxiety, they may use alcohol to reduce tension. Further studies are needed to understand the influence of the serotonin transporter gene on drinking behavior, with special attention given to replication in other ethnic groups.
Does anyone happen to know what the distribution of 5-HTT variations is in various ethnicities and races? There are probably regional differences in distribution well below the level of the major races.
The short version of the serotonin transporter gene also predisposes a person to depression in response to stressful life events.
Among people who suffered multiple stressful life events over 5 years, 43 percent with one version of a gene developed depression, compared to only 17 percent with another version of the gene, say researchers funded, in part, by the National Institute of Mental Health (NIMH). Those with the "short," or stress-sensitive version of the serotonin transporter gene were also at higher risk for depression if they had been abused as children. Yet no matter how many stressful life events they endured, people with the "long" or protective version experienced no more depression than people who were totally spared from stressful life events. The short variant appears to confer vulnerability to stresses, such as loss of a job, breaking up with a partner, death of a loved one, or a prolonged illness, report Drs. Avshalom Caspi and Terrie Moffitt, University of Wisconsin and King's College London, and colleagues, in the July 18, 2003 Science.
The serotonin transporter gene codes for the protein in neurons, brain cells, that recycles the chemical messenger after it's been secreted into the synapse, the gulf between cells. Since the most widely prescribed class of antidepressants act by blocking this transporter protein, the gene has been a prime suspect in mood and anxiety disorders. Yet, its link to depression eluded detection in eight previous studies.
"We found the connection only because we looked at the study members' stress history," noted Moffitt. She suggested that measuring such pivotal environmental events — which can include infections and toxins as well as psychosocial traumas — might be the key to unlocking the secrets of psychiatric genetics.
Although the short gene variant appears to predict who will become depressed following life stress about as well as a test for bone mineral density predicts who will get a fractured hip after a fall, it's not yet ready for use as a diagnostic test, Moffitt cautioned. If confirmed, it may eventually be used in conjunction with other, yet-to-be-discovered genes that predispose for depression in a "gene array" test that could help to identify candidates for preventive interventions. Discovering how the "long" variant exerts its apparent protective effect may also lead to new treatments, added Moffitt.
Everyone inherits two copies of the serotonin transporter gene, one from each parent. The two versions are created by a slight variation in the sequence of DNA in a region of the gene that acts like a dimmer switch, controlling the level of the gene's turning on and off. This normal genetic variation, or polymorphism, leads to transporters that function somewhat differently. The short variant makes less protein, resulting in increased levels of serotonin in the synapse and prolonged binding of the neurotransmitter to receptors on connecting neurons. Its transporter protein may thus be less efficient at stopping unwanted messages, Moffitt suggests.
There is one odd thing about their dataset: half of them had one of each variant. But far more had two long versions than had two short versions.
Moffitt and colleagues followed 847 Caucasian New Zealanders, born in the early l970s, from birth into adulthood. Reflecting the approximate mix of the two gene variants in Caucasian populations, 17 percent carried two copies of the stress-sensitive short version, 31 percent two copies of the protective long version, and 51 percent one copy of each version.
Is this dataset representative of the larger population of New Zealanders? If so, then something interesting is going on. If the carriers of the short and long gene versions were equally likely to reproduce and equally likely to mate with others regardless of whether the others are the same or different for this gene and if half the population was heterozygous for this gene then we'd expect to see equal numbers homozygous for the short and long versions. But in this study group the homozygous short versions were less common than homozygous long versions even though half the study participants were heterozygous short-long.
Is there some kind of preferential mating going on where those who pair up with opposite homozygous types have more children than matings between pairs who are homozygous for the short version? Or are heterozygous people more fecund than the homozygous for this gene? Or are homozygous shorts less likely to mate with their own kind but more likely to have more children when they pair up with a member of the other groups? There are a lot of possibilities and those are just a few of them.
The reseachers ought to survey these people for how many children they've had and at what age. Also, they should test the serotonin transporter genes of their children and the other parents of their children to see if there are any obvious patterns at work.
"We now understand the biological basis of some people's ability to bounce back successfully from adverse life events," said Science's deputy editor, life sciences, Katrina Kelner. "This is tremendously exciting. The research adds to the findings published in Science by the same team last year which showed why certain maltreated children grow up to be healthy adults and certain ones develop antisocial behaviors."
So this is the same research team that published a report showing that a particular variation in the gene for monoamine oxidase-A caused mistreated children to become violent and anti-social.
By age 11, 36 percent of the subjects had been maltreated (8 percent severely), as defined by frequent changes in primary caregiver, rejection by the mother and physical or sexual abuse. Although only 12 percent of the maltreated children had low activity levels of the MAO A, they accounted for 44 percent of their generation's total convictions for assault and other violent crimes.
"As adults, 85 percent of the severely maltreated children who also had the gene for low MAO A activity developed antisocial outcomes, such as violent criminal behavior," says Moffitt. "The combination of maltreatment and the genetic variation magnified the odds by nine times."
On the other hand, the group found that children who had been maltreated but who had higher levels of MAO A were unlikely to develop behavior problems, suggesting that the gene regulating the enzyme does serve a protective function. "The genotype of high MAO A activity," explains Moffitt, "may promote 'trauma resistance.'"
Based on these initial findings, Moffitt says, "The combination of the low-activity MAO A genotype and maltreatment predicts antisocial behaviors about as well as high cholesterol predicts heart disease."
Low levels of the MAO A enzyme may help explain why some abused children are more likely to develop aggressive or criminal behavior, but Moffitt stresses that it does not explain why people are violent: "Low levels of the enzyme did not predict antisocial outcomes in the whole population. It's relation to aggression only emerged when we considered whether the children had been maltreated."
However, the UW-Madison researchers suspect that the MAO A genetic variation may play a similar role in protecting people who have experienced other stressful events, such as car accidents or wars.
Differences in the brain derived neurotrophic factor (BDNF) gene cause differences in memory formation and recall capabilities.
In the new research, reported in the Journal of Neuroscience, Daniel R. Weinberger and his colleagues at the National Institute of Mental Health in Bethesda, Maryland, studied 28 people who carried genes that encoded either the “Val” form or the “Met” form of the BDNF protein.
People with the "Val" form of BDNF are better at recalling visual memories.
The researchers noticed significant differences in brain activity between the two groups during both the encoding and retrieval phases of the task. Those with the “Val” form of the gene were better at remembering pictures than were those with the “Met” form, and they also had greater brain activity during the encoding and retrieval phases of memory.
Remarkably, the interaction between the BDNF val66met genotype and the hippocampal response during encoding accounted for 25% of the total variation in recognition memory performance. These data implicate a specific genetic mechanism for substantial normal variation in human declarative memory and suggest that the basic effects of BDNF signaling on hippocampal function in experimental animals are important in humans.
So you might be thinking that it is better to have two copies of the "Met" form of BDNF. Well, not so fast. It depends on what kind of memory you want to be better at forming and recalling. Earlier work by the same group of scientists showed that the "Val" variant is better for recalling episodic memory.
Drawing on participants in the NIMH intramural sibling study of schizophrenia, Egan and colleagues first assessed their hippocampal function and related it to their BDNF gene types.
Among 641 normal controls, schizophrenia patients, and their unaffected siblings, those who had inherited two copies of the "met" variant scored significantly lower than their matched peers on tests of verbal episodic (event) memory. Most notably, normal controls with two copies of "met" scored 40 percent on delayed recall, compared to 70 percent for those with two copies of "val." BDNF gene type had no significant effect on tests of other types of memory, such as semantic or working memory.
The researchers then measured brain activity in two separate groups of healthy subjects while they were performing a working memory task that normally turns off hippocampus activity. Functional magnetic resonance imaging (fMRI) scans revealed that those with one copy of "met" showed a pattern of activation along the sides of the hippocampus, in contrast to lack of activation among those with two copies of "val."
Next, an MRI scanner was used to measure levels of a marker inside neurons indicating the cell's health and abundance of synapses -- tiny junctions through which neurons communicate with each other. Again, subjects with one copy of "met" had lower levels of the marker, N-acetyl-aspartate (NAA), than matched individuals with two copies of "val." Analysis showed that NAA levels dropped as the number of inherited "met" variants increased, suggesting a possible "dose effect."
Unlike other growth factors, hippocampal BDNF is secreted, in part, in response to neuronal activity, making it a likely candidate for a key role in synaptic plasticity, learning and memory. To explore possible mechanisms underlying the observed "met"- related memory effect, the researchers examined the distribution, processing and secretion of the BDNF proteins expressed by the two different gene variants within hippocampal cells. When they tagged the gene variants with green fluorescent protein and introduced them into cultured neurons, they discovered that "val" BDNF spreads throughout the cell and into the branch-like dendrites that form synapses, while "met" BDNF mostly clumps inside the cell body without being transported to the synapses. To regulate memory function, BDNF must be secreted near the synapses.
"We were surprised to see that 'met' BDNF secretion can't be properly regulated by neural activity," said Lu.
These scientists are tracing the differences in memory recall all the way down to the molecular level.
Neurons transfected with met-BDNF-GFP showed lower depolarization-induced secretion, while constitutive secretion was unchanged. Furthermore, met-BDNF-GFP failed to localize to secretory granules or synapses. These results demonstrate a role for BDNF and its val/met polymorphism in human memory and hippocampal function and suggest val/met exerts these effects by impacting intracellular trafficking and activity-dependent secretion of BDNF.
It is quite possible that there exist variations of other genes which complement either the "Val" or "Met" variations so as to allow superior memory formation and recall for both episodic and visual memories.
A couple of interesting reports just out have identified additional genes with variants that are linked to mental disorders. A research team at the University of California at San Diego has identified a genetic variation of the GRK3 gene that may be responsible for 10% of all cases of bipolar disorder (aka manic depression).
Published in the June 16, 2003 issue of the journal Molecular Psychiatry, the findings indicate that a mutation in a gene that regulates sensitivity to brain neurotransmitters such as dopamine, causes bipolar disorder in as many as 10 percent of bipolar cases. The mutation in this gene, G protein receptorkinase 3 (GRK3), occurs in a portion of the gene called the promoter, that regulates when the gene is turned on.
The research team hypothesizes that this mutation causes the individual to become hypersensitive to dopamine, leading to the mood extremes that characterize biopolar disorder.
A complex and variable illness, bipolar disorder is thought to be caused by multiple genes. Although previous research has suggested candidate genes or general DNA regions where faulty genes may reside, the UCSD study is the first to pinpoint a precise gene involved in the disease.
Also known as manic depression, bipolar disorder is characterized by extreme mood states alternating between euphoric peaks and terrible depression. Current treatments help many who suffer from bipolar disorder, but physicians estimate that one-third to one-half of the 1 million bipolar patients worldwide receive little benefit from existing therapies.
The UCSD scientists used amphetamines in rats to mimic the effect of the manic phase of bipolar disorder and found that GRK3 was upregulated by the administration of amphetamines.
In a parallel study, Kelsoe and collaborators Bob Niculescu, David Segal and Ron Kuczenski, used DNA micro arrays, also called gene chips, to look at 8,000 genes from rats treated with amphetamine so as to mimic the mania of bipolar disorder. This relatively new technology allows scientists to track the expression – the turning on and off – of thousands of genes in a single, high-speed test.
“GRK3 had the largest change in levels of expression, indicating that it played a substantial role in the brain’s response to dopamine and possibly other neurotransmitters,” Kelsoe said. He added that “this was one of the most exhilarating moments for all of us involved. We had the positional piece from the linkage studies, and then the expression data which identified the same gene. We call this convergent functional genomics – identifying a gene based on both its position on a chromosome and on its function.”
One obvious use for this result would be to look at the people who have bipolar disorder due to the GRK3 variant and see if the best drugs for treating them are different than the drugs that work best for people who have bipolar disorder for other reasons. Every time a new genetic variation is linked to some mental disease then drug treatment regimes can be tested for that subset of people suffering from the disorder who have that variation. In the longer run new drugs can be developed that specifically target expression of the gene which is found to be playing a role in the disease.
A gene that codes for the human serotonin transporter has been found to be linked to anxiety. People with a tendency toward anxiety are more likely to abuse drugs and hence one version of serotonin transporter may contribute to drug abuse.
Researchers found that one version of the human serotonin transporter gene (5HTT-LPR) was strongly associated with anxious personalities. Individuals with this gene variant were the sort who find social interaction stressful and may take refuge in substance abuse.
But wait, that is not the only genetic variation that contributes to drug abuse. In a separate result a variation of the D4 dopamine receptor gene has also been found to be linked to a personality trait that contributes to drug abuse.
And a version of the gene for a receptor of the neurotransmitter dopamine - the D4 receptor - was associated with having a more outgoing personality. It is well-established that both these personality traits are more likely to lead to substance misuse.
Leave aside the focus on drug abuse in the reports on these last two results. Here we are seeing the identification of more genetic variations that contribute to personality. There are certainly dozens and perhaps even hundreds more such variants waiting to be found. As DNA sequence assaying technology continues to advance to make it easier and cheaper to test for DNA variations the rate at which personality influencing genetic variations will be found will continue to accelerate.
As each new genetic variant that influences behavior is identified there are predictably people such as one Dr Jonathan Chick who rush forth to proclaim that we still have free will.
He said: "There is no genetic condition that completely removes free will with respect to drinking or smoking.
Well, how does he know there is no genetic condition that at least in some individuals does not make their compulsion to smoke so strong as to be uncontrollable? There are people who have other kinds of completely uncontrollable compulsions. Some bite their lips. Some bang their heads against walls. People with Tourette's can't keep from blurting out all sorts of random thoughts. It is not inconceivable that there are people who have uncontrollable compulsions to smoke. However, whether there are or not is besides the point when it comes to the question of free will because we already know that there are other biochemical conditons which are probably genetically based which cause some people to have uncontrollable compulsions.
There are limits to free will. We are going to learn of many more genetic variations that tilt the odds in various ways to change group average behavior. This fact is disturbing to many. Heck, it is disturbing to me. But if we do not accept it we will do a poor job of dealing with all the implications.
A gene that affects serotonin neuron function in mice has been identified. (my bold emphasis added below)
"We have now shown that Pet-1 is required specifically for fetal development of serotonin neurons," says Deneris. In mice missing this gene, most serotonin neurons fail to be generated in the fetus and the ones that remain are defective. This leads to very low serotonin levels throughout the developing brain, which in turn results in altered behavior in adults. "This is the first gene shown to impact adult emotional behavior through specific control of fetal serotonin neuron development."
Deneris and his colleagues employed sensitive tests of aggression and anxiety to compare the behavior of the knockout mice to wild type mice. One such aggression test measures a mouse's response time to an intruder mouse entering its territory. The Pet-1 knockout mice attacked intruders much more quickly and more often than wild type mice. In fact, knockout mice often would not engage in normal exploratory behavior directed toward the intruder before attacking it. Excessive anxiety-like behavior was evident in another test, measuring the amount of time a mouse spends in open unprotected areas of a test chamber compared to closed protected areas. Unlike normal mice, which will enter and explore an unprotected portion of the test chamber, the Pet-1 knockout mice avoided this area all together, indicating abnormal anxiety-like behavior.
The human and mouse serotonin systems share many anatomical and functional features, and the same Pet-1 gene is present in the human genome. Therefore, Deneris' discovery creates the first animal model for gaining a greater understanding of the causes of abnormal anxiety and aggression brought about through defective early serotonin neuron development. Deneris also sees this knockout mouse being used as a model for screening new drugs that can treat both aggression and anxiety. "If in fact particular genetic variants of Pet-1 are associated with excessive anxiety or violent activity in humans, then tests to detect these variants might be useful for early diagnosis of people who may be at risk for developing these abnormal behaviors," Deneris says. His lab plans more studies in mice to see how the gene affects sleep-wake patterns, learning and memory, and sexual behavior – all functions controlled in part by serotonin.
It seems likely that within 20 or at most 30 years all the genes that influence behavior and mental state will be identified. Work in animal models will lead to the identification of genes that are important in the brain. Declining costs of DNA sequencing will ensure that all the genetic variations will be identified. Once sequencing costs drop low enough large groups of people with different variations will be able to be compared to see if and how they differ in behavior, personality, and intelligence. This will accelerate efforts to identify which variations are important. The most important variations will tend to be found first because they will cause the most dramatic and easily measurable differences within groups.
It will take much longer to learn how all of the mind-influencing genes work in every detail. But long before we understand everything about the brain's function we will at least be able to identify which genes and genomic regulatory areas (i.e. regulatory areas of the genome which affect when and how each gene is expressed) come in multiple versions where the different versions cause humans to differ from each other in how their minds work.
Far more than space, the mind is the final frontier. That we are on the threshold of answering basic questions about the mind seems remarkable. For centuries humans have wondered and argued about human nature. Many have puzzled over why they have felt compelled to do things that were harmful to themselves or to others. They've battled their emotions or wallowed in them. Why is one person shy or another person easily irritated or easily distracted? Why is one person seemingly perpetually happy while another is perpetually sad? Noone has known the answers to these questions. While all the details of how the mind functions will take decades to fully understand we will know many practical consequences of a large number of genetic variations long before that. This information will be useful for a assortment of purposes.
The ability to analyse an individuals's DNA to check for specific variations will be used to speed the diagnosis of mental illness and to choose the most effective treatment. For instance, depression will likely be found to have many different genetic causes. Guided by the knowledge of which genes and which variations of those genes are contributing to a specific case of depression a doctor will be able to choose drugs which have been found most effective in treating patients with that particular contributing set of genetic variations. To do this it will not even be necessary to understand why specific drugs work best with specific genetic variations (though that knowledge will be helpful when it comes). Also, the identification of genetic variations that contribute to depression will serve as a guide for the development of drugs that target the proteins that those genes code for.
The mouse gene in this latest report is linked to aggression. Consider what it will mean for the criminal justice system when someone can be tested for genetic factors that contribute to aggressiveness. If genetic variations become routinely available in criminal trials will judges decide to give longer prison sentences to those who have a genetic propensity toward repeated acts of violence? Or will defense attorneys successfully argue that defendants with genetic variations that are linked to violence can't be held responsible because "their genes made them do it"? Another possibility is that if a convict has a genetic variation that makes him more hostile and if a drug is available that targets that genetic variation to suppress its effects on behavior then a condition of parole might be to require the convict to take the drug that suppresses the aggression-enhancing genetic variation. Advances in neurobiology will at least partially undermine the Western notion of free will and will change our view of individual responsibility.
Mice that do not have the gastrin-releasing peptide (GRP) gene show enhanced learning of fear.
The researchers next explored whether eliminating GRP's activity could affect the ability to learn fear by studying a strain of knockout mice that lacked the receptor for GRP in the brain.
In behavioral experiments, they first trained both the knockout mice and normal mice to associate an initially neutral tone with a subsequent unpleasant electric shock. As a result of the training, the mouse learns that the neutral tone now predicts danger. After the training, the researchers compared the degree to which the two strains of mice showed fear when exposed to the same tone alone — by measuring the duration of a characteristic freezing response that the animals exhibit when fearful.
"When we compared the mouse strains, we saw a powerful enhancement of learned fear in the knockout mice," said Kandel. Also, he said, the knockout mice showed an enhancement in the learning-related cellular process known as long-term potentiation.
"It is interesting that we saw no other disturbances in these mice," he said. "They showed no increased pain sensitivity; nor did they exhibit increased instinctive fear in other behavioral studies. So, their defect seemed to be quite specific for the learned aspect of fear," he said. Tests of instinctive fear included comparing how both normal and knockout mice behaved in mazes that exposed them to anxiety-provoking environments such as open or lighted areas.
"These findings reveal a biological basis for what had only been previously inferred from psychological studies — that instinctive fear, chronic anxiety, is different from acquired fear," said Kandel.
In additional behavioral studies, the researchers found that the normal and knockout mice did not differ in spatial learning abilities involving the hippocampus, but not the amygdala, thus genetically demonstrating that these two anatomical structures are different in their function.
The regulation of the expression of a large variety of genes in the brain varies from person to person because there are genetic variations in genes and regulatory areas that govern how much each gene makes its resulting protein product(s). Personality types will eventually be shown to have genetic causes. This will of course lead to a desire on the part of prospective parents to exercise some control over which personality-related genetic variations their offspring will get. Genetic engineering of personality will become a hotly debated topic when it becomes clear to the general public that this will be technically possible.
The Val/Val variants might boost schizophrenia risk.
Those who performed poorly on visual memory recall tests were found to have two characteristics: less brain activity in the region known to regulate long-term memory, and the presence of a particular form of the BDNF gene.
The gene comes in two forms (known as "met" and "val"), and the research found that people with one or two copies of "met" had less memory recall.
The COMT gene comes in two common forms or alleles, Val and Met. As with any gene, people inherit one allele from each parent. Participants with the Val/Val version of the COMT gene performed worse on the card-sorting test than those with Val/Met or Met/Met variations. The researchers also examined transmission of the gene from 126 "heterozygous" parents (who had the Val/Met version) to their schizophrenic children. They found that 75 schizophrenics inherited the Val allele, compared to 51 who inherited the Met allele, suggesting that the Val allele increases risk slightly.
The researchers think the Val allele may compromise dopamine function in the prefrontal cortex, impairing working memory. The authors write, "Thus the COMT Val allele … might add to or interact with other causes of prefrontal malfunction in those at risk for schizophrenia and thereby increase their susceptibility."
It is possible that either Val/Val or Val/Met offer advantages in other areas. Likely that is the case or else the Val variant would have been selected out of existence.
The region they've narrowed the search to is also linked to autism. However, since they haven't yet narrowed the search to a single gene it is not yet proven that the same gene is involved in both disorders. However, what is important here is that the search for a major genetic contributor to ADHD is getting close to a culprit:
UCLA Neuropsychiatric Institute researchers have localized a region on chromosome 16 that is likely to contain a risk gene for Attention Deficit Hyperactivity Disorder, the most prevalent childhood-onset psychiatric disorder.
Their research, published in the October edition of the American Journal of Human Genetics, suggests that the suspected risk gene may contribute as much as 30 percent of the underlying genetic cause of ADHD and may also be involved in a separate childhood onset disorder, autism.
Pinpointing a gene with a major role in ADHD will help researchers and clinicians better understand the biology of this disorder and likely lead to the development of improved diagnosis, treatment and early intervention.
"We know there are about 35,000 genes in the human genome. By highlighting this region on chromosome 16, we have narrowed our search for a risk gene underlying ADHD to some 100 to 150 genes," said Susan Smalley, principal investigator of the study and co-director of the Center for Neurobehavioral Genetics at the UCLA Neuropsychiatric Institute.
Once it becomes possible to control whether progeny get the genes that contribute to mental disorders it will become possible to totally eliminate a large variety of mental disorders from some future generation. This will result in an intergenerational difference in attitudes as the average younger person will be brighter and happier than any previous generation.
How important will personal genetic sequencing be in changing mating decisions? It partly depends on how many genetic variations are found to influence personality and behavior (obviously health and appearance genes will be important in mating choices as well) . Therefore I'm going to post every good study I come across that shows links between genetic variations, personality, and behavior.
This is a report about a gene that codes for monoamine oxidase-A which breaks down neurotransmitters (there are even MAO inhibitor drugs used for treating mental illness). The genetic variation studied here sounds like its in the gene expression regulatory region. Note how children with the high risk variation become a threat in adult life only if abused as children:
The results were clear. Only 12% of the group had both abused childhoods and low-activity promoter regions, yet this group accounted for 44% of those who had criminal convictions for violence. Fully 85% of the 12% showed some form of routine anti-social behaviour. The next most anti-social combination (high-activity promoters and an abused childhood) resulted in only about 45% of men showing routine anti-social behaviour, while only a quarter of those who had had tranquil childhoods were anti-social in adulthood, regardless of their promoter type.
This result also begins to explain the phenomenon of kids who have terrible childhoods who turn out to be wonderful adults. They just don't have the requisite genetic makeup to be antisocial.