Dentate gyrus microstructure is associated with resilience after exposure to maternal stress across two human cohorts

van Dijk, M. T. et al. (2023) Dentate gyrus microstructure is associated with resilience after exposure to maternal stress across two human cohorts. Biological Psychiatry, (doi: 10.1016/j.biopsych.2023.06.026) (PMID:37393047) (In Press)

Abstract

Background: Maternal stress (MS) is a well-documented risk factor for impaired emotional development in offspring. Rodent models implicate the dentate gyrus (DG) of the hippocampus in the effects of MS on offspring depressive-like behaviors, but mechanisms in humans remain unclear. Here, we test across two independent cohorts whether MS is associated with depressive symptoms and with DG micro- and macro-structural alterations in offspring. Methods: We analyzed DG DTI mean diffusivity (DG-MD) and volume in a 3-Generation Family Risk for Depression study (TGS; n=69, mean age 35.0) and the Adolescent Brain Cognitive Development Study (ABCD; n=5196, mean age 9.9) using generalized estimating equation models and mediation analysis. MS was assessed by the Parenting Stress Index (in TGS) and a measure compiled from the Adult Response Survey (ABCD). PHQ-9 and rumination scales (TGS) and Child Behavior Checklist (ABCD) measured offspring depressive symptoms at follow-up. Schedule for Affective Disorders and Schizophrenia–Lifetime interview measured depression diagnoses. Results: Across cohorts, MS was associated with future symptoms and higher DG-MD (indicating disrupted microstructure) in offspring. Higher DG-MD was associated with higher symptom scores measured 5 years (TGS) and 1-year (ABCD) after MRI. In ABCD, DG-MD is increased in high-MS offspring who have depressive symptoms at follow-up, but not in offspring who remain resilient or whose mother had low MS. Conclusions: Converging results across two independent samples extend previous rodent studies and suggest a role for the DG in exposure to MS and offspring depression.

• Item Type: Articles
• Additional Information: This project was supported by the National Institute of Mental Health R01MH036197 (MMW, JP) and by National Institute of Mental Health K99MH129611 (MvD), an AFSP Young Investigator Award YIG-R-001-19 (MvD), National Institute of Mental Health R00MH108719 (CA), NARSAD Young Investigator Award (CA).
• Status: In Press
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cullen, Dr Breda
• Authors: van Dijk, M. T., Talati, A., Kashyap, P., Desai, K., Kelsall, N., Gameroff, M., Aw, N., Abraham, E., Cullen, B., Cha, J., Anacker, C., Weissman, M. M., and Posner, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Journal Name: Biological Psychiatry
• Publisher: Elsevier
• ISSN: 0006-3223
• ISSN (Online): 1873-2402
• Published Online: 29 June 2023
• Copyright Holders: Copyright © 2023 Elsevier Inc. on behalf of Society of Biological Psychiatry
• First Published: First published in Biological Psychiatry 2023
• Publisher Policy: Reproduced in accordance with the publisher copyright policy