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.
|Share |||Randall Parker, 2003 June 17 04:37 PM Brain Genetics|