Shared Gene Expression Alterations in Schizophrenia and Bipolar Disorder

Shao, Ling; Vawter, Marquis P.

doi:10.1016/j.biopsych.2007.11.010

« Previous Next »Biological Psychiatry
Volume 64, Issue 2 , Pages 89-97, 15 July 2008

Shared Gene Expression Alterations in Schizophrenia and Bipolar Disorder

Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, School of Medicine, University of California, Irvine, California.

Received 26 June 2007; received in revised form 6 November 2007; accepted 8 November 2007. published online 15 January 2008.

Background

Schizophrenia and bipolar disorder together affect approximately 2.5% of the world population, and their etiologies are thought to involve multiple genetic variants and environmental influences. The analysis of gene expression patterns in brain may provide a characteristic signature for each disorder.

Methods

RNA samples from the dorsolateral prefrontal cortex (Brodmann area 46) consisting of individuals with schizophrenia (SZ), bipolar disorder (BPD), and control subjects were tested on the Codelink Human 20K Bioarray platform. Selected transcripts were validated by quantitative real-time polymerase chain reaction (PCR). The strong effects of age, gender, and pH in the analysis of differential gene expression were controlled by analysis of covariance (ANCOVA). Criteria for differential gene expression were 1) a gene was significantly dysregulated in both BPD and SZ compared with control subjects and 2) significant in ANCOVA analysis with samples that have a pH above the median of the sample.

Results

A list of 78 candidate genes passed these two criteria in BPD and SZ and was overrepresented for functional categories of nervous system development, immune system development and response, and cell death. Five dysregulated genes were confirmed with quantitative Q-PCR in both BPD and SZ. Three genes were highly enriched in brain expression (AGXT2L1, SLC1A2, and TU3A). The distribution of AGXT2L1 expression in control subjects versus BPD and SZ was highly significant (Fisher's Exact Test, p < 10⁻⁰⁶).

Conclusions

These results suggest a partially shared molecular profile for both disorders and offer a window into discovery of common pathophysiology that might lead to core treatments.

Key Words: AGXT2L1, antipsychotic medication, apoptosis, bipolar disorder, BUB1B, dorsolateral prefrontal cortex, EMX2, ERBB2, FGF2, FTH1, IL2RA, LGALS3, MAFG, microarray, neurogenesis, NFATC1, PVR, quantitative PCR, RERG, schizophrenia, SLC1A2, SMCY, SMO, SOX9, TU3A, TXNIP