Polygenic risk for depression and anterior and posterior hippocampal volume in children and adolescents

Hailee Hurtado; Melissa Hansen; Jordan Strack; Uku Vainik; Alexandra L Decker; Budhachandra Khundrakpam; Katherine Duncan; Amy S Finn; Donald J Mabbott; Emily C Merz

doi:10.1016/j.jad.2023.10.068

Polygenic risk for depression and anterior and posterior hippocampal volume in children and adolescents

J Affect Disord. 2024 Jan 1:344:619-627. doi: 10.1016/j.jad.2023.10.068. Epub 2023 Oct 18.

Authors

Affiliations

¹ Department of Psychology, Colorado State University, Fort Collins, CO, USA.
² University of Tartu, Tartu, Estonia; Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
³ Department of Brain and Cognitive Sciences and McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
⁵ Department of Psychology, University of Toronto, Toronto, ON, Canada.
⁶ Department of Psychology, University of Toronto, Toronto, ON, Canada.; Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.; Department of Psychology, Hospital for Sick Children, Toronto, ON, Canada.
⁷ Department of Psychology, Colorado State University, Fort Collins, CO, USA. Electronic address: emily.merz@colostate.edu.

PMID: 37858734
PMCID: PMC10842073 (available on 2025-01-01)
DOI: 10.1016/j.jad.2023.10.068

Abstract

Background: Depression 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.

Methods: Participants 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.

Results: Children and adolescents with higher polygenic risk for depression were more likely to have a parent with a history of anxiety/depression. Higher polygenic risk for depression was significantly associated with smaller anterior but not posterior hippocampal volume. PGS-EA was not associated with anterior or posterior hippocampal volumes.

Limitations: Participants in these analyses were all of European ancestry.

Conclusions: Polygenic 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 the design of more effective, personalized treatment strategies.

Declarations of interest: none.

Declarations of interest: None.

Keywords: Brain structure; Depression; Genetics; hippocampus.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adolescent
Child
Depression* / diagnostic imaging
Depression* / genetics
Educational Status
Female
Genome-Wide Association Study*
Hippocampus / diagnostic imaging
Humans
Magnetic Resonance Imaging
Male

Grants and funding

RC2 DA029475/DA/NIDA NIH HHS/United States