Genetic risk for depression linked to muted brain response to wins and losses

Novel imaging research indicates that young adults with a higher genetic risk for depression showed less brain activity in several areas when responding to rewards and punishments. The study also uncovered notable differences between men and women. The findings from this new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, highlight potential early indicators for depression before clinical symptoms fully manifest.

Depression is one of the most common mental health conditions, and many people with depression have trouble processing rewards and punishments. It is known that genetics plays a role in depression, but it is not yet clear how genetic risk might affect the brain's response to positive and negative experiences. The researchers of the current study explored this connection in young adults before symptoms of depression fully developed.

In one of the first studies to show how genetic risk for depression might affect how the brain responds to good and bad outcomes in everyday decision-making, researchers explored how neural markers of reward and punishment processing reflect the overall genetic risks for depression, whether these markers are distinct from those associated with depression severity, and whether men and women show differences in these genetically informed neural markers.

"The study's focus on individuals who are not yet diagnosed with depression paves the way for a better understanding of how genetic predisposition interacts with brain function in the context of reward and punishment, opening up new avenues for early detection and targeted therapies for depression," comments Editor-in-Chief of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging Cameron S. Carter, MD, University of California Irvine.

Researchers evaluated functional MRI brain scans and genotyping data from nearly 900 healthy twins or siblings (ages 22-35) in the Human Connectome Project (HCP) while they played a gambling game that involved winning or losing money. They looked at how the participants' brains responded during wins and losses, and how that related to their genetic risk for depression.

Lead investigator Chiang-Shan R. Li, MD, PhD, Department of Psychiatry and Department of Neuroscience, Yale University School of Medicine, and Inter-department Neuroscience Program and Wu Tsai Institute, Yale University, reports, "We found that individuals with higher genetic risk for depression showed less activity in brain areas linked to attention and decision-making like the frontal, parietal, and occipital cortical regions of the brain. One area, the posterior cingulate cortex, was strongly associated with punishment but not reward processing. This potential punishment-specific region opens up interesting new questions. We also observed sex-dependent neural responses that suggest potentially sex-specific neurobiological pathways linking genetic risk to depression."

This research shows that genetic risk for depression can quietly influence how the brain reacts to everyday rewards and setbacks—even before someone feels depressed. These early brain markers could help us detect who is at risk and find better ways to intervene before symptoms appear. The gender differences identified make this work exceptionally timely, as the field moves toward more personalized mental healthcare."

Yu Chen, PhD, lead author of the article, Department of Psychiatry, Yale University School of Medicine