Resurrecting the So-Called 'Depression Gene'::Genes May Play Role in Response to Adversity

Resurrecting the So-Called 'Depression Gene'::Genes May Play Role in Response to Adversity

  8:01:00 PM    Science Lover

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University of Michigan Health System researchers have found new evidence that our genes help determine our susceptibility to depression.

Our genes help determine our susceptibility to depression, 
new research suggests. (Credit: iStockphoto/
Nicholas Belton)

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."

Srijan Sen, M.D., Ph.D, an assistant professor of psychiatry at the University of Michigan 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 to 2010 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," says Sen.

The U-M analysis supports previous findings that individuals who had a short allele on a particular area the serotonin gene had a harder time bouncing back from trauma than those with long alleles.

Rudolf Uher, Ph.D., 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 major strength of the analysis is that it is the first such work that included all studies that were available on the topic," Uher says. "And it gives a very clear answer: the 'short' variant of the serotonin transporter does make people more sensitive to the effects of adversity."

The authors of the initial study from 2003 were also excited by the U-M team's results.

"Their careful and systematic approach reveals why the JAMA meta-analysis got it wrong," says Terrie Moffitt, Ph.D., a professor at Duke University and one of the authors of the 2003 study. "We hope that the same journalists who were so hasty to publish a simplistic claim in 2009 will cover this more thoughtful new analysis."

When the U-M team restricted their analysis to the 14 studies included in the 2009 JAMA paper, they also failed to find a genetic link, suggesting to Sen that the scope of the analysis, not the methodology, was responsible for the new findings.

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. For instance, 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.

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.

"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," Sen says.

Funding: The research was supported by grants from the National Institutes of Health, University of Michigan Depression Center and Studienstiftung des Deutschen Volkes.

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

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Men and Women Respond Differently to Stress

Men and Women Respond Differently to Stress

  10:50:00 AM    Science Lover

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Age and gender play a major role in how people respond to stress, according to a new study on 20-to-64-year-olds. Published in the journal Psychophysiology, the investigation was led by scientists from the Université de Montréal and the Montreal Heart Institute in collaboration with colleagues from the Université du Québec à Montréal and McGill University.

"Our findings suggest that women who are more defensive are at increased cardiovascular risk, whereas low defensiveness appears to damage the health of older men," says Bianca D'Antono, a professor at the Université de Montréal Department of Psychiatry and a Montreal Heart Institute researcher.

Defensiveness is a trait characterized by avoidance, denial or repression of information perceived as threatening. In women, a strong defensive reaction to judgment from others or a threat to self-esteem will result in high blood pressure and heart rate. Contrarily, older men with low defensive reactions have a higher cardiovascular rates.

The study was conducted on 81 healthy working men and 118 women. According to Dr. Jean-Claude Tardif a Université de Montréal professor and Montreal Heart Institute researcher, the physiological response to stress in women and older men is linked to this desire of maintaining self-esteem and securing social bonds.

"The sense of belonging is a basic human need," says D'Antono. "Our findings suggest that socialization is innate and that belonging to a group contributed to the survival of our ancestors. Today, it is possible that most people view social exclusion as a threat to their existence. A strong defensive reaction is useful to maintain one's self-esteem faced with this potential threat."

As part of the experiment, participants completed four tasks of varying stress levels. The first task involved reading a neutral text on Antarctica's geography before a person of the same sex. The second and third tasks involved role-playing in which participants followed a script where they were sometimes agreeable and sometimes aggressive. The final task involved a non-scripted debate on abortion.

Heart rate and blood pressure were measured during each of these tasks as was the level of cortisol in saliva. Results showed that women and older men had elevated cardiovascular, autonomic and endocrine responses to stress -- all potentially damaging to their health. The research team cautions, however, that more studies are needed to evaluate the long-term effects of defensiveness and its association to stress response patterns in disease development.

This study was supported by the Canadian Institutes of Health Research and the Fonds de la recherche en santé du Québec.

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