Genetic Risk for Depression Impacts Neural Responses to Rewards and Setbacks

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 studyopens in new tab/window in Biological Psychiatry: Cognitive Neuroscience and Neuroimagingopens in new tab/window, 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.”

Lead author of the article Yu Chen, PhD, Department of Psychiatry, Yale University School of Medicine, concludes, “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.”

Notes for editors

The article is "Polygenic Risks for Depression and Neural Responses to Reward and Punishment in Young Adults," by Yu Chen, Huey-Ting Li, Xingguang Luo, Guangfei Li, Jaime S. Ide, and Chiang-Shan R. Li (https://doi-org.ucc.idm.oclc.org/10.1016/j.bpsc.2025.05.008opens in new tab/window). It appears online in Biological Psychiatry: Cognitive Neuroscience and Neuroimagingopens in new tab/window, published by Elsevier.

The article is openly available athttps://www.biologicalpsychiatrycnni.org/article/S2451-9022(25)00167-3/fulltextopens in new tab/window.

Copies of this paper are also available to credentialed journalists upon request; please contact Rhiannon Bugno at [email protected]opens in new tab/window. Journalists wishing to interview the study’s authors should contact Yu Chen, PhD, at [email protected]opens in new tab/window.

The authors’ affiliations and disclosures of financial and conflicts of interest are available in the article.

Cameron S. Carter, MD, is Chair of the Department of Psychiatry & Human Behavior at the University of California, Irvine School of Medicine. His disclosures of financial and conflicts of interest are available hereopens in new tab/window.

This study is supported by NIH grants AG072893 and DA051922.

About Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Biological Psychiatry: Cognitive Neuroscience and Neuroimagingopens in new tab/window is an official journal of the Society of Biological Psychiatryopens in new tab/window, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal focuses on studies using the tools and constructs of cognitive neuroscience, including the full range of non-invasive neuroimaging and human extra- and intracranial physiological recording methodologies. It publishes both basic and clinical studies, including those that incorporate genetic data, pharmacological challenges, and computational modeling approaches. The 2024 Journal Impact Factor^TM score, from Clarivate, for Biological Psychiatry: Cognitive Neuroscience and Neuroimaging is 4.8.www.sobp.org/bpcnniopens in new tab/window

엘스비어 소개

엘스비어는 첨단 정보와 의사결정 지원 분야의 글로벌 선도 기업으로 100년 넘게 과학과 헬스케어의 발전을 지원하며 인류 진보에 기여해 왔습니다. 우리는 170개국 이상에서 학술 및 기업 연구 커뮤니티, 의사, 간호사, 미래의 의료 전문가와 교육자들을 지원합니다. 근거에 기반한 신뢰할 수 있는 과학·의학 콘텐츠와 최첨단 AI 기술을 결합해 중요한 통찰과 혁신적인 솔루션을 제공해, 의미있는 성과를 이루도록 돕고 있습니다. 또한 다양성과 지속 가능성을 제품과 기업 문화 전반에 내재화하며, 우리가 속한 커뮤니티와 협력합니다. 엘스비어 재단opens in new tab/window은 전 세계에서 연구와 보건 파트너십을 지원합니다.

엘스비어는 전문가 및 기업 고객에게 정보 기반의 분석과 의사결정 도구를 제공하는 글로벌 기업 RELXopens in new tab/window의 일원입니다. 자세한 내용은 www.elsevier.com에서 확인할 수 있으며, 소셜미디어 @elsevierconnect를 통해 최신 소식을 받아보실 수 있습니다.