Dentate gyrus volume deficit in schizophrenia

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1267-1277
Number of pages11
JournalPsychological medicine
Volume50
Issue number8
DOIs
StatePublished - Jun 1 2020

Keywords

  • genetics
  • genome-wide association analysis
  • hippocampus
  • imaging
  • subfield

ASJC Scopus subject areas

  • Applied Psychology
  • Psychiatry and Mental health

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