Dentate gyrus volume deficit in schizophrenia

Soichiro Nakahara; Jessica A Turner; Vince D Calhoun; Kelvin O Lim; Bryon Mueller; Juan R Bustillo; Daniel S O'Leary; Sarah McEwen; James Voyvodic; Aysenil Belger; Daniel H Mathalon; Judith M Ford; Fabio Macciardi; Mitsuyuki Matsumoto; Steven G Potkin; Theo G M van Erp

doi:10.1017/S0033291719001144

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Dentate gyrus volume deficit in schizophrenia

Journal article

Peer reviewed

Dentate gyrus volume deficit in schizophrenia

Soichiro Nakahara, Jessica A Turner, Vince D Calhoun, Kelvin O Lim, Bryon Mueller, Juan R Bustillo, Daniel S O'Leary, Sarah McEwen, James Voyvodic, Aysenil Belger, …

Psychological medicine, Vol.50(8), pp.1-1277

06/03/2019

DOI: 10.1017/S0033291719001144

PMCID: PMC7068799

PMID: 31155012

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https://www.ncbi.nlm.nih.gov/pmc/articles/7068799View

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Abstract

Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined. Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed. This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = -0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = -0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10-8, 95% CI 7.0-14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume. This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.

genetics

subfield

hippocampus

imaging

genome-wide association analysis

Details

Title: Subtitle: Dentate gyrus volume deficit in schizophrenia
Creators: Soichiro Nakahara - Clinical Translational Neuroscience Laboratory,Department of Psychiatry and Human Behavior,University of California Irvine,Irvine, CA 92617,USA
Jessica A Turner - The Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) {Georgia State, Georgia Tech, Emory},Atlanta, GA 30300,USA
Vince D Calhoun - The Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) {Georgia State, Georgia Tech, Emory},Atlanta, GA 30300,USA
Kelvin O Lim - Department of Psychiatry,University of Minnesota,Minneapolis, MN 55454,USA
Bryon Mueller - Department of Psychiatry,University of Minnesota,Minneapolis, MN 55454,USA
Juan R Bustillo - Departments of Psychiatry & Neuroscience,University of New Mexico,Albuquerque, NM 87131,USA
Daniel S O'Leary - Department of Psychiatry,University of Iowa,Iowa City, IA 52242,USA
Sarah McEwen - Department of Psychiatry,University of California,San Diego, La Jolla, CA 92093,USA
James Voyvodic - Brain Imaging and Analysis Center, Duke University Medical Center,Durham, NC 27710,USA
Aysenil Belger - Department of Psychiatry,University of North Carolina at Chapel Hill,Chapel Hill, NC 27599,USA
Daniel H Mathalon - Department of Psychiatry,Weill Institute for Neurosciences, University of California,San Francisco, San Francisco, CA 94143,USA
Judith M Ford - Department of Psychiatry,Weill Institute for Neurosciences, University of California,San Francisco, San Francisco, CA 94143,USA
Fabio Macciardi - Department of Psychiatry and Human Behavior,University of California Irvine,Irvine, CA 92617,USA
Mitsuyuki Matsumoto - Virtual Venture Unit, Psychiatry, Drug Discovery Research,Astellas Pharma Inc.,21, Miyukigaoka, Tsukuba, Ibaraki 305-8585,Japan
Steven G Potkin - Department of Psychiatry and Human Behavior,University of California Irvine,Irvine, CA 92617,USA
Theo G M van Erp - Clinical Translational Neuroscience Laboratory,Department of Psychiatry and Human Behavior,University of California Irvine,Irvine, CA 92617,USA
Resource Type: Journal article
Publication Details: Psychological medicine, Vol.50(8), pp.1-1277
DOI: 10.1017/S0033291719001144
PMID: 31155012
PMCID: PMC7068799
NLM abbreviation: Psychol Med
ISSN: 1469-8978
eISSN: 1469-8978
Publisher: England
Grant note: UL1 TR000153 / NCATS NIH HHS P20 GM103472 / NIGMS NIH HHS R01 MH094524 / NIMH NIH HHS R21 MH097196 / NIMH NIH HHS U24 RR021992 / NCRR NIH HHS U24 RR025736 / NCRR NIH HHS
Language: English
Date published: 06/03/2019
Academic Unit: Psychiatry
Record Identifier: 9984003409502771

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