Neuropsychopharmacology Reports (Sep 2023)

Lipid‐correlated alterations in the transcriptome are enriched in several specific pathways in the postmortem prefrontal cortex of Japanese patients with schizophrenia

  • Wataru Arihisa,
  • Takeshi Kondo,
  • Katsushi Yamaguchi,
  • Junya Matsumoto,
  • Hiroki Nakanishi,
  • Yasuto Kunii,
  • Hiroyasu Akatsu,
  • Mizuki Hino,
  • Yoshio Hashizume,
  • Shumpei Sato,
  • Shinji Sato,
  • Shin‐Ichi Niwa,
  • Hirooki Yabe,
  • Takehiko Sasaki,
  • Shuji Shigenobu,
  • Mitsutoshi Setou

DOI
https://doi.org/10.1002/npr2.12368
Journal volume & issue
Vol. 43, no. 3
pp. 403 – 413

Abstract

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Abstract Aims Schizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. There were studies showing that the phospholipid abnormalities in subjects with schizophrenia (Front Biosci, S3, 2011, 153; Schizophr Bull, 48, 2022, 1125; Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933). Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in subjects with schizophrenia (Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933; Schizophr Res, 215, 2020, 493; J Psychiatr Res, 47, 2013, 636; Int J Mol Sci, 22, 2021). For exploring the signaling pathways contributing to the lipid changes in previous study (Sci Rep, 7, 2017, 6), we performed two types of transcriptome analyses in subjects with schizophrenia: an unbiased transcriptome analysis solely based on RNA‐seq data and a correlation analysis between levels of gene expression and lipids. Methods RNA‐Seq analysis was performed in the postmortem prefrontal cortex from 10 subjects with schizophrenia and 5 controls. Correlation analysis between the transcriptome and lipidome from 9 subjects, which are the same samples in the previous lipidomics study (Sci Rep, 7, 2017, 6). Results Extraction of differentially expressed genes (DEGs) and further sequence and functional group analysis revealed changes in gene expression levels in phosphoinositide 3‐kinase (PI3K)‐Akt signaling and the complement system. In addition, a correlation analysis clarified alterations in ether lipid metabolism pathway, which is not found as DEGs in transcriptome analysis alone. Conclusions This study provided results of the integrated analysis of the schizophrenia‐associated transcriptome and lipidome within the PFC and revealed that lipid‐correlated alterations in the transcriptome are enriched in specific pathways including ether lipid metabolism pathway.

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