MedWire News: Schizophrenia and bipolar disorder patients appear to have a partially shared molecular profile that may point to the discovery of a common pathophysiology and novel treatments, say US scientists.
The etiologies of schizophrenia and bipolar disorder are thought to involve multiple genetic variants and environmental influences. Owing to the two conditions being viewed largely through their clinical presentations and historical classifications, they are treated as independent classes of disease.
An examination of gene expression patterns in the brain may provide a characteristic signature for each disorder, say Marquis Vawter, from the University of California at Irvine, and team.
The researchers therefore studied RNA samples from Brodmann area 46 in the dorsolateral prefrontal cortex of 32 schizophrenia patients, 29 bipolar disorder patients, and 27 controls, aged an average of 42.9 years, 45.3 years, and 44.4 years, respectively.
The team used a bioarray platform to analyze the samples, and quantitative real-time polymerase chain reaction (PCR) to validate selected transcripts. Differential gene expression was defined as a gene significantly dysregulated in both bipolar disorder and schizophrenia and significance on ANCOVA analysis in samples with a pH above the median.
Brain pH was significantly decreased in both schizophrenia and bipolar disorder patients in comparison with controls, at 6.48 and 6.50 versus 6.64, respectively, while the refrigeration interval was significantly increased in the patient groups.
The results, published in the journal Biological Psychiatry, show that 78 candidate genes met the two criteria for differential gene expression in both bipolar disorder and schizophrenia, and these were commonly associated with nervous system development, immune system development and response, and cell death.
Five of the dysregulated genes were confirmed in bipolar disorder and schizophrenia, with three - alanine-glyoxylate aminotransferase 2-like 1 (AGXT2L1), solute carrier family 1 (glial high affinity glutamate transporter) member 2 (SLC1A2), and down regulated in renal cell carcinoma 1(TU3A) - highly enriched in brain expression. AGXT2L1 had a highly significant expression distribution in controls in comparison with bipolar disorder and schizophrenia patients.
The team concludes: "The shared genes merit further consideration in future neurogenomic and cognitive studies of schizophrenia and bipolar disorder candidate genes."
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