U-M Health System researchers have found new evidence that our genes help determine our susceptibility to depression.
Their findings, published online in the Archives of General Psychiatry, challenge a 2009 study that called the genetic link into question and add new support to earlier research hailed as a medical breakthrough.
In the summer of 2003, scientists announced they had discovered a connection 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.
The journal Science ranked the findings among the top discoveries of the year and the director of the National Institute of Mental Health proclaimed, “It is a very important discovery and a real advance for the field.”
That excitement was dampened in 2009, however, after the research was called into question by a study published in the Journal of the American Medical Association. The New York Times reported that analysis, which examined results from 14 different studies, showed the initial findings had “not held up to scientific scrutiny.”
Today Dr. Srijan Sen, an assistant professor of psychiatry at the Medical School, and his colleagues are presenting a new, broader analysis of the follow-up studies to date. The U-M team examined 54 studies dating from 2001-10 and encompassing nearly 41,000 participants — making it the largest analysis of the serotonin gene’s relationship to depression.
“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,” Sen says.
The U-M 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.
Rudolf Uher, a clinical lecturer at the Institute of Psychiatry in London, says the U-M research will help cut through the debate about the genetic connection and refocus the field on making new advances to help those affected by mental illness.
The U-M analysis found robust support for the 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.
But that’s also common sense. Different stressful life events may have very different effects, Sen says.
Still, the study results don’t mean that everyone should run out and get a genetic test; additional susceptibility from having a short allele is only one factor among many that determine how an individual responds to stress, Sen says.
Additional research will help to map an individual’s genetic profile for depression.
Additional U-M authors are Margit Burmeister, Kerby Shedden and former graduate student Katja Karg.
