Researchers believe psychiatric disorders triggered by genes, stress

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Most researchers now believe that serious psychiatric disorders are triggered by both genetic susceptibility and stresses in the environment.

Joel Gelernter, a geneticist at Yale University, believes he and his colleagues have found such a genetic vulnerability for people who go on to get post-traumatic stress disorder or depression.

It involves a gene variant known as 5HTTLPR, which controls a protein that affects the amount of a brain chemical known as serotonin. There are two common forms of the variant — known as S for short and L for long . Those with the S variant are more likely to get PTSD and depression if they are exposed to stress or adversity.

Dr. Gelernter said people with the S variant have fewer copies of a protein that helps the brain reabsorb serotonin after it has been used in the brain, and because the condition exists from birth, it probably means that those people’s brains produce less serotonin overall.

Most major antidepressant drugs work by making more serotonin available in the brain, and “we can imagine that extra serotonin can help buffer the brain against the stresses that might lead to PTSD or depression,”

He compared the impact of the 5HTTLPR gene variant to a decorative fountain that recirculates its water through a nozzle. “Imagine 5HTTLPR as the nozzle size — S is smaller, L is larger — and serotonin as the water,” he said, “and think of a situation where your brain might need serotonin, for example to respond to stress.”

Those with the S-sized nozzle would have more difficulty mobilizing enough serotonin to respond to traumatic situations, he said.

People who inherit two copies of the L variant of the gene, he said, seem to be less susceptible to PTSD and depression, but at the same time, they have a higher risk for obsessive-compulsive disorder.

That drives home the lesson that in the brain, “you often find evidence of balancing forces” that can affect brain chemicals and behavior, he said.

If the S variant of the 5HTTLPR gene makes people vulnerable to psychiatric problems, why hasn’t evolution weeded it out of the population?

Dr. Gelernter doesn’t know for sure, but he pointed out that the L version increases the risk for other problems, and said there is considerable evidence linking mood disorders to artists and other creative individuals.

“Highly creative people in the arts and music and playwriting have a higher rate of affective disorder than people in the general population,” he said, and that trait may have been vital in helping humans prosper, even if it came at the risk of some psychiatric disorders.

Mark Roth:, 412-263-1130 and on Twitter: @markomar.

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