Since 2003, the link between a gene that regulates the neurotransmitter serotonin and an individual’s ability to rebound from serious emotional trauma, such as childhood physical or sexual abuse has been hotly debated. Today, University of Michigan Health System researchers have found new evidence that our genes help determine our susceptibility to depression.

The journal Science ranked the findings among the top discoveries of the year, and the director of the National Institute of Mental Health has stated, “It is a very important discovery and a real advance for the field.”

The controversy started seven and a half years ago when researchers at Duke University first published reference to this genetic link and caused a tremendous stir in the mental health community. However in 2009 the research was questioned in a study published in the Journal of the American Medical Association (JAMA). That same year The New York Times reported that analysis, which examined results from 14 different studies, showed the initial 2003 findings had “not held up to scientific scrutiny.”

Today in the Archives of General Psychiatry online, Srijan Sen, M.D., Ph.D, an assistant professor of psychiatry at the University of Michigan Medical School, and his colleagues present a broader analysis of the follow-up studies recorded to date. The Michigan team examined 54 studies existing from 2001 to 2010 comprised of nearly 41,000 participants.

This has been the largest analysis of the serotonin gene’s relationship to depression ever conducted.

Dr. Sen states:

“This brings us one step closer to being able to identify individuals who might benefit from early interventions or to tailor treatments to specific individuals. When we included all the relevant studies, we found that an individual’s genetic make-up does make a difference in how he or she responds to stress.”

The University of Michigan analysis supports previous findings that individuals who had a short allele on a particular area of the serotonin gene had a harder time bouncing back from trauma than those with long alleles. An allele is an alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome. These DNA codings determine distinct traits that can be passed on from parents to offspring.

It is now confirmed that there is a link between sensitivity to stress and a short allele in those who had been mistreated as children and in people suffering with specific, severe medical conditions. Only a marginal relationship was found in those who had undergone stressful life events.

Note though that different stressful life events may have very different effects, Sen says. For example, there is no reason to think that the effects of divorce, at a biological level, would be similar to the effects of losing your home or being physically assaulted.

Terrie Moffitt, Ph.D., a professor at Duke University and one of the authors of the 2003 study proclaimed:

“Their careful and systematic approach reveals why the JAMA meta-analysis got it wrong. We hope that the same journalists who were so hasty to publish a simplistic claim in 2009 will cover this more thoughtful new analysis.”

However, when the U of M team restricted their analysis to the 14 studies as the 2009 study did, they also failed to find a genetic link. Dr. Sen believes that the scope of the analysis, and not the methodology, was responsible for the new findings.

From across the pond, London clinical researcher Rudolf Uher, Ph.D. at the Institute of Psychiatry in London says the American research will refocus the field on making new advances to help those affected by mental illness by helping cut through the debate about the genetic connection.

Usher continues:

“The major strength of the analysis is that it is the first such work that included all studies that were available on the topic and it gives a very clear answer: the ‘short’ variant of the serotonin transporter does make people more sensitive to the effects of adversity.”

Additional research will help to map an individual’s genetic profile for depression. It is a groundbreaking discovery that this is even possible.

Additional U-M Authors: Margit Burmeister, Ph.D., Kerby Shedden, Ph.D., former graduate student Katja Karg

Reference: Archives of General Psychiatry 10.1001/archgenpsychiatry.2010.189

Written by Sy Kraft, B.A.