TY - JOUR
T1 - Dentate gyrus volume deficit in schizophrenia
AU - Nakahara, Soichiro
AU - Turner, Jessica A.
AU - Calhoun, Vince D.
AU - Lim, Kelvin O.
AU - Mueller, Bryon
AU - Bustillo, Juan R.
AU - O'Leary, Daniel S.
AU - McEwen, Sarah
AU - Voyvodic, James
AU - Belger, Aysenil
AU - Mathalon, Daniel H.
AU - Ford, Judith M.
AU - MacCiardi, Fabio
AU - Matsumoto, Mitsuyuki
AU - Potkin, Steven G.
AU - Van Erp, Theo G.M.
N1 - Publisher Copyright:
Copyright © Cambridge University Press 2019.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.Methods 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.Results 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.Conclusions 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.
AB - Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.Methods 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.Results 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.Conclusions 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.
KW - genetics
KW - genome-wide association analysis
KW - hippocampus
KW - imaging
KW - subfield
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U2 - 10.1017/S0033291719001144
DO - 10.1017/S0033291719001144
M3 - Article
C2 - 31155012
AN - SCOPUS:85066482579
SN - 0033-2917
VL - 50
SP - 1267
EP - 1277
JO - Psychological medicine
JF - Psychological medicine
IS - 8
ER -