Can Genetics Help Predict Depression After a Major Stressor?

Experiencing a major life stressor is a risk factor for developing depression. What patterns of depressive symptoms follow a major stressor, and can genetic information help predict which pattern an individual may experience? Work recently published by Katharina Schultebraucks and colleagues in JAMA Psychiatry addresses these questions.

These investigators utilized data from the Health and Retirement Study (HRS), a prospective longitudinal study of U.S. citizens born between 1931 and 1947. Participants in this study were age 50 years and older, and of European ancestry. They were assessed on “mental and physical health-related aspects” of their lives every two years between 1992 and 2010. Genetic information was also collected from some of the individuals. The severity of depressive symptoms was assessed with a standardized depression scale, the 10-item version of the Center for Epidemiologic Studies-Depression (CES-D).

The researchers identified previous studies that used HRS data to examine patterns of depressive symptoms before and after a major life stressor. They then examined whether an individual’s genetic profile could be helpful in predicting which pattern of depressive symptoms an individual would experience.

They included data from studies that assessed depressive symptoms following one of five major stressors: bereavement, myocardial infarction, divorce, cancer, and job loss. Individuals experiencing more than one stressor were excluded from the study, as were those with no available genetic information. In all, data from 2,071 individuals were included in the analysis.

Four Patterns of Depressive Symptoms

The previous studies found that individuals followed one of four patterns of depressive symptoms after the stressor. One pattern was characterized by few depressive symptoms prior to the stressor followed by increasing symptoms after the stressor that rose above the threshold for clinically significant depression. This pattern was labeled “emerging depression;” 8 percent of individuals in the combined data set followed this pattern. A second pattern was labeled “recovery.” This pattern was characterized by elevated depressive symptoms prior to the event and steadily improving symptoms following the event; 8 percent of individuals followed this pattern. The third pattern followed a “preexisting chronic” course, meaning that elevated depressive symptoms existed both prior to and after the stressor; about 6 percent of individuals followed this pattern. The largest group of participants (79 percent) was categorized as “resilient.” These individuals had minimal depressive symptoms prior to and after the stressor.

The major research question addressed in the Schultebraucks et al. study was whether genetic information that can be obtained from a blood test would be useful in predicting the outcome. To approach this question, the investigators utilized polygenic scores (PGSs), which combine “genome-wide contributions into an overall score reflecting an individual’s overall genetic propensity for a given trait or disorder.” Combining PGSs “increase[s] the predictive power for psychosocial outcomes.” In the current study, the investigators calculated PGSs related to 21 psychiatric or other health-related conditions for each individual. An analytic approach called “deep neural net” modeling was utilized to determine if the genetic profiles could predict which of the four depressive patterns individuals would follow.

Study Results

The results were encouraging. The genetic information allowed reasonably accurate predictions of which depressive pattern an individual experienced following a major life stressor. The accuracy of the prediction was highest for the preexisting chronic group and lowest for the resilient group.

Thus, genetic information was effective in predicting the pattern of depressive symptoms following a life stressor. If these results are confirmed by others, it suggests that genetic information could possibly assist in designing the most appropriate therapeutic strategy for an individual experiencing a major life stressor. It will also be important to determine whether this analytic strategy is helpful in younger individuals and individuals with other major stressors.

It should not be surprising that genes are very much involved in how individuals respond to major life stressors. The possibility of being able to use genetic information to predict how much help a person may require to deal with such a stressor is exciting.

This column was written by Eugene Rubin, MD, PhD, and Charles Zorumski, MD.