Researchers identify specific genes, brain regions, and cognitive features associated with depression

In studies that examine the depressed brain, researchers were able to identify specific genes, molecules, brain regions, and cognitive features that are associated with the disorder. The findings will be presented on Monday, November 13, 10–11 a.m. EST at Neuroscience 2023, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

More than 8% of adults in the United States suffer from severe depression, and the percentage is higher among specific groups, including adolescents and older adults. Depression is a complex condition that includes many different genetic components and environmental risk factors. Scientists are working to understand the exact mechanisms in the brain that correspond with the risk or development of depression in the hopes of developing earlier identification and more effective treatment options.

New findings show that:

• Genetic variants seem to correspond with risks for depression as indicated by changes in brain structure in adolescents, in ways both sex-specific and not. (Yu Chen, Yale University)
• In depression, distributed brain regions involved in attention and emotion processing (i.e., the salience network) have increased size/representation in adolescents -; a potential biological target for early intervention. (Sanju Koirala, University of Minnesota)
• Higher depressive symptoms have a stronger detrimental effect on reasoning in older adults, who were studied for several years. (Denise Park, University of Texas at Dallas)
• Adolescents diagnosed with depression have unique epigenetic signatures in blood samples. (Cecilia Flores, McGill University)

Identifying brain markers and risk factors for depression gets us closer to diagnosing and treating the disorder more effectively. This research will ultimately allow us to pursue a more targeted approach, especially with regards to early intervention and personalized treatment strategies in vulnerable populations."

Diego A. Pizzagalli, professor of psychiatry at Harvard Medical School and moderator of the press conference

This research was supported by national funding agencies including the National Institutes of Health and private funding organizations. Find out more about depression and the brain on BrainFacts.org.

Monday, November 13, 2023

10–11 a.m. EST

Walter E. Washington Convention Center, Room 202B

Press conference summary

• These presentations identify dysregulations in the brain and peripheral blood that are correlated with depression. Three of the studies focus on adolescents and identify specific markers (genetic variants, brain networks, and microRNAs) that suggest a connection with risk for developing the disorder. The third study focuses on depression over time and establishes a connection between depression and decline in reasoning in older age.

Gray matter volumetric correlates of depression and genetic risks in children: preliminary evidence from the Adolescent Brain Cognition Development (ABCD) study

Yu Chen, [email protected], Abstract PSTR098.07

• Researchers studied 6,186 research participants (2,774 of which were girls ages 9–10) from the ABCD project to learn how genetic risks manifest in young people with depression; the study used voxel-based morphometry and computed polygenic risk scores (PRS) for depression.
• For every participant, depression symptoms were assessed and PRS and gray matter volumes (GMV) across the brain were computed. In all subjects, more depressive symptoms and greater PRS were associated with smaller regional GMV across the brain, including frontal, parietal, temporal, insular and subcortical regions, with boys and girls alone showing most of GMV deficits in association with depression symptoms and PRS, respectively.
• These findings suggest that, with regard to depression in children, there are brain structural markers shared by depression symptoms and genetic risks -; but only some are sex-specific.

Individual variation in the size of salience network relates to depression

Sanju Koirala, [email protected], Abstract PSTR098.16

• Major depression has its origins in childhood, making it crucial to identify brain markers to prevent and treat the condition.
• In a study of 5,530 adolescents from the Adolescent Brain Cognition Development (ABCD) Study, researchers found an increased size and representation of the salience network implicated in attention and emotion processing in participants with higher depressive symptoms.
• This finding reveals a promising neural target for identifying and treating depression in youth.

Aging and depression trajectories on cognition

Denise Park, [email protected], Abstract PSTR307.10

• Researchers investigated the relationship between depression and cognitive performance, predicting that depression would worsen with cognitive decline.
• The study included 264 participants ages 20–89 who completed cognitive measures and questionnaires over an average of nearly four years. Analysis showed that baseline depressive symptoms peaked in young adulthood, declined through middle age, and returned to a smaller degree in very old age.
• They also found that, for older adults, higher depressive symptoms resulted in a more detrimental effect on reasoning, which provides evidence of associations between depression and cognitive decline.

MicroRNA expression profiles from peripheral blood may serve as biomarkers for depression risk in children and adolescents

Cecilia Flores, [email protected], Abstract PSTR225.12

• Researchers are working to identify reliable molecular indicators for risk of depression using microRNA profiles in blood samples from adolescents, using a minimally-invasive method.
• They identified several differentially expressed microRNAs in dry blood spot samples from adolescents diagnosed with clinical depression as well as in blood of children from an ethnically different background and who exhibit high depression scores. A common microRNA is elevated in both cohorts.
• The identified microRNAs are highly expressed in the brain and their predicted gene targets are involved in neurodevelopmental and cognitive processes.
• The levels of microRNAs linked to depression in blood samples can predict future severity of symptoms.