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. 2023 Oct:335:111710.
doi: 10.1016/j.pscychresns.2023.111710. Epub 2023 Aug 28.

Auditory oddball hypoactivation in schizophrenia

Soichiro Nakahara  1 , Alie G Male  2 , Jessica A Turner  3 , Vince D Calhoun  4 , Kelvin O Lim  5 , Bryon A Mueller  5 , Juan R Bustillo  6 , Daniel S O'Leary  7 , James Voyvodic  8 , Aysenil Belger  9 , Adrian Preda  10 , Daniel H Mathalon  11 , Judith M Ford  12 , Guia Guffanti  13 , Fabio Macciardi  10 , Steven G Potkin  10 , Theo G M Van Erp  14
Affiliations

Auditory oddball hypoactivation in schizophrenia

Soichiro Nakahara et al. Psychiatry Res Neuroimaging. 2023 Oct.

Abstract

Individuals with schizophrenia (SZ) show aberrant activations, assessed via functional magnetic resonance imaging (fMRI), during auditory oddball tasks. However, associations with cognitive performance and genetic contributions remain unknown. This study compares individuals with SZ to healthy volunteers (HVs) using two cross-sectional data sets from multi-center brain imaging studies. It examines brain activation to auditory oddball targets, and their associations with cognitive domain performance, schizophrenia polygenic risk scores (PRS), and genetic variation (loci). Both sample 1 (137 SZ vs. 147 HV) and sample 2 (91 SZ vs. 98 HV), showed hypoactivation in SZ in the left-frontal pole, and right frontal orbital, frontal pole, paracingulate, intracalcarine, precuneus, supramarginal and hippocampal cortices, and right thalamus. In SZ, precuneus activity was positively related to cognitive performance. Schizophrenia PRS showed a negative correlation with brain activity in the right-supramarginal cortex. GWA analyses revealed significant single-nucleotide polymorphisms associated with right-supramarginal gyrus activity. RPL36 also predicted right-supramarginal gyrus activity. In addition to replicating hypoactivation for oddball targets in SZ, this study identifies novel relationships between regional activity, cognitive performance, and genetic loci that warrant replication, emphasizing the need for continued data sharing and collaborative efforts.

Keywords: Cognition; Functional MRI; Genome-wide association analysis; Imaging; Polygenic risk score; Replication.

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Conflict of interest statement

Declaration of Competing Interest Dr. Nakahara is employed by Astellas Pharma Inc. Dr. Bustillo consulted with Novartis and Otsuka Pharmaceuticals. Dr. Mathalon is a consultant for Bristol-Myers Squibb and consulted for Roche Pharmaceuticals. Dr. Preda consulted for Boehringer-Ingelheim. Dr. Potkin has financial interests in Bristol-Myers Squibb, Eisai, Inc., Eli Lilly, Forest Laboratories, Genentech, Janssen Pharmaceutical, Lundbeck, Merck, Novartis, Organon, Pfizer, Roche, Sunovion, Takeda Pharmaceutical, Vanda Pharmaceutical, Novartis, Lundbeck, Merck, Sunovion and has received grant funding from Amgen, Baxter, Bristol-Myers Squibb, Cephalon, Inc., Eli Lilly, Forest Laboratories, Genentech, Janssen Pharmaceutical, Merck, Otsuka, Pfizer, Roche, Sunovion, Takeda Pharmaceutical, Vanda Pharmaceutical, NIAAA, NIBIB, NIH/NCRR, University of Southern California, UCSF, UCSD, Baylor College of Medicine. The remaining authors declare no potential conflict of interest. None of the authors of this manuscript are affiliated with or receive compensation from NeuroComp Systems, Inc., MATRICS Assessment, Inc., or Neurcog Trials, Inc.

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