January 25, 2003
Mouse Gene Linked To Anxiety, Aggression

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.

Share |      Randall Parker, 2003 January 25 04:47 PM  Brain Genetics

Bob said at January 25, 2003 9:44 PM:

Hmmm... It's interesting that the Pet-1 knockout mice exhibit behaviour very similar to humans with post-traumatic stress disorder. (PTSD)

I wonder if traumatic stress has a permanent effect on seratonin production or reception in humans? Or if some humans are more prone to PTSD due to seratonin irregularities in the first place?

Well, maybe google answered my question.

Perhaps, I should go for a walk.

Susan Miller said at March 16, 2004 3:26 PM:

There needs to be more information before we start making blanket policies regarding humans and the future of the human race. For example, is the study duplicated in other animals, and what is the result? Mice are already known for having high activity levels so maybe the research could only be relevant to already high level humans, such as the type A personality. This would change the way we think about applying policies in that it MAY change the applicability due to social and economic factors. Type A stock broker in handcuffs vs. Type A street kid? Also, what were the conditions of the mouse when it was en utero? What was it fed? How was it raised? Was it brought up the same way as other mice? What about the other mice? Was the other mouse a "normal" mouse, or was it covered in pheremones before the study began? If the study didn't expressly prohibit it, then that is theoretically plausible. Finally, who funded the research? What were their ties to the criminal justice system, the mental health care system, and the pharmaceutical industry? Did the funding occur when a new drug was coming on the market to treat aggressive behavior? When did the research begin? Was it during the Clinton (Gore) Administration, or other? These questions need to be asked, especially when the research affects the civil liberties of human beings. The constitutional rights of countless Americans are already being trampled on in the name of "care" and "prevention", and other misapplied terms to assist in feeding the legal drug industry and drain the social security system. It is so very ironic that the generation of the sixties is doing that to their children and parents (taking away estates in the process, also in the name of care)but explainable. --Susan

PunditPal said at April 14, 2004 5:35 PM:

I find it amusing to suggest that anything other than learning and environment causes aggression.

Sure, it is plausable to suggest that certain brain chemistries might affect impulse control, but I guarantee that a person needs to learn how to punch or kick before those movements approach anything close to a threat, which is what defines aggression. In fact, psychology defines aggression as a learned behaviour. The fact that I, myself, have never learned how to punch or kick effectively is proof that should I develop a lack of impulse control, my actions will only be threatening to the extent I have "perfected" those aggressive behaviours. Looking for a genetic cause for the actual behaviours we call "aggression" is like looking for a genetic cause for utensil use.

Mike Smith said at July 15, 2005 4:11 AM:

I disagree that aggression is purely learnt. A person can be aggressive without being a threat, so the fact that they're no good at punching or kicking means little.
More relevant research is the effect of removing genes coding for two different forms of nitric oxide synthase, nNOS and eNOS; removing one causes extreme aggression, amongst other effects, whilst removing the other causes docility. In addition, there are several medical conditions that cause behavioural changes including increased aggression, without any change in external stimuli which could cause a change in learned response.
A more realistic attitude towards aggression is therefore to accept that it is contributed to both by genetic "predestination", so to speak, and also by learned behaviour.

Bowie Lam said at September 14, 2005 2:03 PM:

I surely agreed that people are usually inherited the relevant character/behaviors, not only Depression and Anxiety. As one of my close friend, she is extremely agressive and impulsive, in spite of she is a well-educated person and ever feel guilty to her offensive behaviors. Perhaps it's true, everybody can't escape from predestination. The only way to combat with those negative thinking and actions are try to read more positive message, to hang out with more decent people and to engage in more healthy activities. I believe even the character can't be change thoroughly but to say the least, negative behaviors can be under control and so the frequencies of conflicts can be reduced.

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