Polygenic Risk for Depression and Anterior and Posterior Hippocampal Volume in Children and Adolescents

Abstract

AbstractBackgroundDepression has frequently been associated with smaller hippocampal volume. The hippocampus varies in function along its anterior-posterior axis, with the anterior hippocampus more strongly associated with stress and emotion processing. The goals of this study were to examine the associations among parental history of anxiety/depression, polygenic risk scores for depression (PGS-DEP), and anterior and posterior hippocampal volumes in children and adolescents. To examine specificity to PGS-DEP, we examined associations of educational attainment polygenic scores (PGS-EA) with anterior and posterior hippocampal volume.MethodsParticipants were 350 3– to 21-year-olds (46% female). PGS-DEP and PGS-EA were computed based on recent, large-scale genome-wide association studies. High-resolution, T1-weighted magnetic resonance imaging (MRI) data were acquired, and a semi-automated approach was used to segment the hippocampus into anterior and posterior subregions.ResultsChildren and adolescents with higher PGS-DEP were more likely to have a parent with a history of anxiety/depression. Higher PGS-DEP was significantly associated with smaller anterior but not posterior hippocampal volume. PGS-EA were not associated with anterior or posterior hippocampal volumes.LimitationsParticipants in these analyses were all of European ancestry.ConclusionsPolygenic risk for depression may lead to smaller anterior but not posterior hippocampal volume in children and adolescents, and there may be specificity of these effects to PGS-DEP rather than PGS-EA. These findings may inform the earlier identification of those in need of support and in the future could inform the design of more effective, personalized treatment strategies.