Hippocampal Subfield Transcriptome Analysis in Schizophrenia Psychosis

We have previously demonstrated functional and molecular changes in hippocampal subfields in individuals with schizophrenia (SZ) psychosis associated with hippocampal excitability. In this study, we use RNA-seq and assess global transcriptome changes in the hippocampal subfields, DG, CA3, and CA1 from individuals with SZ psychosis and controls to elucidate subfield-relevant molecular changes. We also examine changes in gene expression due to antipsychotic medication in the hippocampal subfields from our SZ ON- and OFF-antipsychotic medication cohort. We identify unique subfield-specific molecular profiles in schizophrenia postmortem samples compared to controls, implicating astrocytes in DG, immune mechanisms in CA3, and synaptic scaling in CA1. We show a unique pattern of subfield-specific effects by antipsychotic medication on gene expression levels with scant overlap of genes differentially expressed by SZ disease effect versus medication effect. These hippocampal subfield changes could provide the basis for previously observed hippocampal SZ pathology and explain the lack of full efficacy of conventional antipsychotic medication on SZ symptomatology. With further characterization, the identified distinct molecular profiles of the DG, CA3, and CA1 in SZ psychosis may serve to identify potential hippocampal-based therapeutic targets. We compared hippocampal subfield-specific transcriptome profiling from individuals with schizophrenia and healty controls. We analyzed genome-wide expression levels in adult dentate gyrus (DG), cornu Ammonis 1 (CA1) and cornu Ammonis 3 (CA3) from 13 individuals with schizophrenia and 13 healthy controls. Gene expression was balanced for technical, biological, and surrogate covariates.