Hippocampal subfield transcriptome analysis in schizophrenia psychosis

Jessica Marie Perez, Stefano Berto, Kelly Gleason, Subroto Ghose, Chunfeng Tan, Tae Kyung Kim, Genevieve Konopka, Carol A. Tamminga

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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 with 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 serve to confirm and extend our previous model of SZ and can explain the lack of full efficacy of conventional antipsychotic medication on SZ symptomatology. With future characterization using single-cell studies, the identified distinct molecular profiles of the DG, CA3, and CA1 in SZ psychosis may serve to identify further potential hippocampal-based therapeutic targets.

Original languageEnglish (US)
Pages (from-to)2577-2589
Number of pages13
JournalMolecular psychiatry
Volume26
Issue number6
DOIs
StatePublished - Jun 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Hippocampal subfield transcriptome analysis in schizophrenia psychosis'. Together they form a unique fingerprint.

Cite this