Region-specific sex differences in the hippocampus

van Eijk, Liza, Hansell, Narelle K., Strike, Lachlan T., Couvy-Duchesne, Baptiste, de Zubicaray, Greig I., Thompson, Paul M., McMahon, Katie L., Zietsch, Brendan P., and Wright, Margaret J. (2020) Region-specific sex differences in the hippocampus. NeuroImage, 215. 116781.

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Abstract

The hippocampus is a brain region critical for learning and memory, and is also implicated in several neuropsychiatric disorders that show sex differences in prevalence, symptom expression, and mean age of onset. On average, males have larger hippocampal volumes than females, but findings are inconclusive after adjusting for overall brain size. Although the hippocampus is a heterogenous structure, few studies have focused on sex differences in the hippocampal subfields – with little consensus on whether there are regionally specific sex differences in the hippocampus after adjusting for brain size, or whether it is important to adjust for total hippocampal volume (HPV). Here, using two young adult cohorts from the Queensland Twin IMaging study (QTIM; N ​= ​727) and the Human Connectome Project (HCP; N ​= ​960), we examined differences between males and females in the volumes of 12 hippocampal subfields, extracted using FreeSurfer 6.0. After adjusting the subfield volumes for either HPV or brain size (brain segmentation volume (BSV)) using four controlling methods (allometric, covariate, residual and matching), we estimated the percentage difference of the sex effect (males versus females) and Cohen’s d using hierarchical general linear models. Males had larger volumes compared to females in the parasubiculum (up to 6.04%; Cohen’s d ​= ​0.46) and fimbria (up to 8.75%; d ​= ​0.54) after adjusting for HPV. These sex differences were robust across the two cohorts and multiple controlling methods, though within cohort effect sizes were larger for the matched approach, due to the smaller sub-sample. Additional sex effects were identified in the HCP cohort and combined (QTIM and HCP) sample (hippocampal fissure (up to 6.79%), presubiculum (up to 3.08%), and hippocampal tail (up to −0.23%)). In contrast, no sex differences were detected for the volume of the cornu ammonis (CA)2/3, CA4, Hippocampus-Amygdala Transition Area (HATA), or the granule cell layer of the dentate gyrus (GCDG). These findings show that, independent of differences in HPV, there are regionally specific sex differences in the hippocampus, which may be most prominent in the fimbria and parasubiculum. Further, given sex differences were less consistent across cohorts after controlling for BSV, adjusting for HPV rather than BSV may benefit future studies. This work may help in disentangling sex effects, and provide a better understanding of the implications of sex differences for behaviour and neuropsychiatric disorders.

Item ID: 67587
Item Type: Article (Research - C1)
ISSN: 1095-9572
Keywords: Hippocampus; Hippocampal subfields; volume; sex; gender; controlling methods
Copyright Information: © 2020 The Author(s). Published by Elsevier Inc.
Funders: The University of Queensland (UQ), National Institutes of Health (NIH), National Health and Medical Research Council (NHMRC)
Projects and Grants: NIH project ROI HD HD050735; NIH Award 1U54EB020403-01, subaward no. 56929223, NHMRC Grant 1009064, NHMRC Grant 496682
Research Data: https://doi.org/10.14264/uql.2019.465
Date Deposited: 06 May 2021 05:19
FoR Codes: 52 PSYCHOLOGY > 5202 Biological psychology > 520202 Behavioural neuroscience @ 50%
52 PSYCHOLOGY > 5205 Social and personality psychology > 520502 Gender psychology @ 20%
52 PSYCHOLOGY > 5202 Biological psychology > 520207 Social and affective neuroscience @ 30%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280121 Expanding knowledge in psychology @ 100%
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