Support from others during stressful times can moderate the impact of genetic depression risk

Support from others during stressful times can moderate the impact of genetic depression risk

Support from others during stressful times can moderate the impact of genetic depression risk

Abstract: Social support during stressful periods helps reduce the risk of developing symptoms in people with a genetic predisposition to depression.

Source: University of Michigan

Supporting a person when they are stressed is always a good idea. But a new study suggests that support may be especially important for someone whose genetic makeup makes them more likely to develop depression.

The study shows the importance of social support in mitigating the risk of developing depressive symptoms in general, using data from two very different groups of people under stress: new doctors in their most intensive training year and elderly people whose spouses have recently died.

But the biggest effect was seen in those who had the most genetic variations that increase the risk of depression.

The paper uses a measure of genetic risk called the polygenic risk score, which is based on decades of research into which small variations in certain genes are associated with depression risk.

Compared to individuals in the study who had low polygenic risk scores for depression, physicians and widows with higher risk scores had higher rates of depression after losing social support, but also had lower rates of depression when they gained social support during stressful periods .

The study, published in American Journal of Psychiatry by the University of Michigan team, suggests that more could be done to target social support to those who can benefit the most.

Genes, stress and social connections

“Our data show wide variability in the level of social support individuals received during these stressful times and how it changed over time,” said first author Jennifer Cleary, MS, a UM psychology doctoral student conducting her research with senior author Srijan Sen, MD, Ph.D., Faculty of Medicine, UM.

“We hope that these findings, which include genetic risk scores as well as measures of social support and depressive symptoms, shed light on gene-environment interactions, and in particular the importance of social connectedness in depression risk.”

Sen, who is director of the Eisenberg Family Depression Center and a professor of psychiatry and neuroscience, adds that while genetic research is uncovering more DNA variations associated with vulnerability to depression, learning how these variations lead to depression is critical.

“Further understanding of the different genetic profiles associated with vulnerability to loss of social support, insufficient sleep, excessive work stress and other risk factors could help us develop personalized guidelines for depression prevention,” he said.

“Meanwhile, these findings reaffirm how important social connections, social support, and individual sensitivity to the social environment are as factors in well-being and depression prevention.”

Different populations, similar patterns

The new study used data from two long-term studies that both record genetic, mood, environmental and other data from the population of participating individuals.

One is the Intern Health Study, which enrolls first-year medical residents (also called interns) across the United States and abroad, and which Sen directs.

The second is the Study of Health and Retirement, which is based at the Institute for Social Research of the UM.

Data for the new paper came from 1,011 interns training at hospitals across the country, nearly half of whom were women, and from 435 recently widowed women, 71% women, who had available data from surveys taken before and after the death of their spouses.

In trainees, as Sen and his team showed in previous work, depressive symptoms rose dramatically (126%) during a stressful year of training that included long and irregular work hours—often in environments far from friends and family.

In widows and widowers, depressive symptoms increased by 34% compared to their scores before widowhood. That correlates with past research showing that losing a spouse can be one of the biggest stressors in a person’s life, Cleary said.

Crossover effect

The researchers then combined the depression symptom findings with each person’s polygenic risk score for depression and their individual responses to questions about relationships with friends, family, and other social supporters.

Most interns have lost the social support of their pre-internship days—which fits well with the common experience of leaving the place where they attended medical school and going to a new environment where they may not know anyone.

Interns who had the highest polygenic risk scores and who also lost social support had the highest scores on measures of depressive symptoms later in the stressful internship year.

However, those with the same high level of genetic risk who received social support had much less depressive symptoms. In fact, it was lower even than their peers at low genetic risk, regardless of what happened to their social support. Researchers call this the “crossover effect.”

Unlike interns, some widows reported increased social support following the loss of a spouse, potentially because friends and family stepped in to offer help or just listen.

But the crossbreeding effect was also visible in them. Widows with a high genetic risk for depression who received social support showed a much smaller increase in depressive symptoms than their peers with a similar genetic risk who lost social support after the loss of a spouse.

Support from others during stressful times can moderate the impact of genetic depression risk
But the biggest effect was seen in those who had the most genetic variations that increase the risk of depression. The image is in the public domain

There were also some widows who lost social support or experienced no change in support, and whose depressive symptoms did not change. Cleary notes that future work will be important to look at the history of this group in light of the care they may have provided for a spouse with a long-term illness.

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The team also hopes that other researchers will study the same interaction of genetic risk, stress, and social support in other populations.

In the meantime, Cleary and Sen say, the message for anyone going through stressful times or watching a friend or relative going through stressful times is to reach out and maintain or strengthen social bonds.

This can be beneficial for both the person under stress and the person addressing them, they note.

Reducing the level of ongoing stress a person faces, whether it’s at work, at school, after a personal loss, or in family situations, can be critical.

Although the study did not examine the role of professional mental health help, individual and group therapy is an important option for those who have developed depression or other mental health problems.

About this news about genetics and depression research

Author: Press office
Source: University of Michigan
Contact: Press Office – University of Michigan
Picture: The image is in the public domain

Original research: Closed access.
Polygenic risk and social support in predicting depression under stress” Jennifer L. Cleary et al. American Journal of Psychiatry


Polygenic risk and social support in predicting depression under stress


Despite significant progress in identifying genomic variations associated with major depression, the mechanisms by which genomic and environmental factors together influence depression risk remain unclear. Genomically conditioned sensitivity to the social environment may be one mechanism linking genomic variation and depressive symptoms. The authors assessed whether social support affects the likelihood of developing depression differently across the spectrum of genomic risk in two samples who experienced significant life stress: 1,011 first-year physicians (interns) in the Intern Health Study (IHS) and 435 recently widowed Health and Retirement Study participants. (HRS).


Depressive symptoms and social support of the participants were assessed with questionnaires administered before and after life stress. Polygenic risk scores (PRS) for major depressive disorder were calculated for both samples.

The results:

Depressive symptom scores increased by 126% after starting an internship in the IHS sample and by 34% after widowhood in the HRS sample. There was an interaction between PRS depression and change in social support in predicting depressive symptoms in both IHS samples (incidence rate ratio [IRR]=0.96, 95% CI=0.93, 0.98) and the HRS sample (IRR=0.78, 95% CI=0.66, 0.92), with higher depression PRS associated with greater sensitivity to changes in social support. Johnson-Neyman intervals indicated a crossover effect, with losses and gains in social support moderating the effect of PRS on depressive symptoms. (Johnson-Neyman interval in the IHS sample, -0.02, 0.71; in the HRS sample, -0.49, 1.92).


The study’s findings suggest that individuals at high genomic risk for developing heightened depressive symptoms in adverse social conditions also benefit more from a nurturing social environment.


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