Diurnal rhythms in gene expression in the prefrontal cortex in schizophrenia

Marianne L Seney,Kelly Cahill,George Tseng,Wei Zong,John F Enwright,Ryan W Logan,Colleen A Mcclung,Zhiguang Huo

doi:10.1038/s41467-019-11335-1

Marianne L Seney, Kelly Cahill + Show 6 more

Open Access

https://doi.org/10.1038/s41467-019-11335-1

Copy DOI

Abstract

Schizophrenia is associated with disrupted cognitive control and sleep-wake cycles. Here we identify diurnal rhythms in gene expression in the human dorsolateral prefrontal cortex (dlPFC), in schizophrenia and control subjects. We find significant diurnal (24 h) rhythms in control subjects, however, most of these transcripts are not rhythmic in subjects with schizophrenia. Instead, subjects with schizophrenia have a different set of rhythmic transcripts. The top pathways identified in transcripts rhythmic only in subjects with schizophrenia are associated with mitochondrial function. Importantly, these rhythms drive differential expression patterns of these and several other genes that have long been implicated in schizophrenia (including BDNF and GABAergic-related transcripts). Indeed, differential expression of these transcripts is only seen in subjects that died during the night, with no change in subjects that died during the day. These data provide insights into a potential mechanism that underlies changes in gene expression in the dlPFC with schizophrenia.

Highlights

IntroductionWe identify diurnal rhythms in gene expression in the human dorsolateral prefrontal cortex (dlPFC), in schizophrenia and control subjects
Schizophrenia is associated with disrupted cognitive control and sleep-wake cycles
Our data demonstrates that subjects with schizophrenia have a set of genes that display a diurnal rhythm in the dorsolateral prefrontal cortex (dlPFC), while losing rhythmicity of genes that are normally rhythmic in control subjects

Summary

Introduction

We identify diurnal rhythms in gene expression in the human dorsolateral prefrontal cortex (dlPFC), in schizophrenia and control subjects. Differential expression of these transcripts is only seen in subjects that died during the night, with no change in subjects that died during the day These data provide insights into a potential mechanism that underlies changes in gene expression in the dlPFC with schizophrenia. Several studies have identified differential gene expression in numerous transcripts in human cortical regions in subjects with schizophrenia, these studies do not consider potential effects of circadian rhythms in gene expression. We performed a similar time-of-death analysis using RNAsequencing (RNA-seq) data generated by the CommonMind Consortium[13] comparing healthy comparison (control) subjects to subjects with schizophrenia

Methods

Results

Conclusion