Subcortical volumes in offspring with a multigenerational family history of depression - A study across two cohorts.

Background: Having multiple previous generations with depression in the family increases offspring risk for psychopathology. Parental depression has been associated with smaller subcortical brain volumes in their children, but whether two prior generations with depression is associated with further decreases is unclear.
Methods: Using two independent cohorts, 1) a Three-Generation Study (TGS, N = 65) with direct clinical interviews of adults and children across all three generations, and 2) the Adolescent Brain Cognitive Development Study (ABCD, N = 10,626) of 9-10 year-old children with family history assessed by a caregiver, we tested whether having more generations of depression in the family was associated with smaller subcortical volumes (using structural MRI).
Results: In TGS, caudate, pallidum and putamen showed decreasing volumes with higher familial risk for depression. Having a parent and a grandparent with depression was associated with decreased volume compared to having no familial depression in these regions. Putamen volume was associated with depression at eight-year follow-up. In ABCD, smaller pallidum and putamen were associated with family history, which was driven by parental depression, regardless of grandparental depression.
Limitations: Discrepancies between cohorts could be due to interview type (clinical or self-report) and informant (individual or common informant), sample size or age. Future analyses of follow-up ABCD waves will be able to assess whether effects of grandparental depression on brain markers become more apparent as the children enter young adulthood.
Conclusions: Basal ganglia regional volumes are significantly smaller in offspring with a family history of depression in two independent cohorts.
Competing Interests: Declaration of competing interest Dr. Weissman receives funds from NIMH and Columbia University Institute for Developmental Sciences and book royalties from Perseus Press and Oxford Press. Dr. Posner has received research support from Takeda (formerly Shire) and Aevi Genomics and consultancy fees from Innovative Science and AlphaSights. None of these present a conflict of interest with or have influenced the research presented in this article.
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