Shared gene expression alterations in schizophrenia and bipolar disorder.
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.
Shao
Ling
L
Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, School of Medicine, University of California, Irvine, California 92697-4260, USA. mvawter@uci.edu
Vawter
Marquis P
MP
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D014644:Genetic Variation / Q000235:genetics; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000503:physiopathology; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D012931:Social Environment; D000637:Transaminases / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D027342:Excitatory Amino Acid Transporter 2; C403503:FAM107A protein, human; D050491:Glutamate Plasma Membrane Transport Proteins; D009687:Nuclear Proteins; C493397:SLC1A2 protein, human; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase