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Differences in lymphocyte electron transport gene expression levels between subjects with bipolar disorder and normal controls in response to glucose deprivation stress.

Naydenov AV, MacDonald ML, Ongur D, Konradi C

Laboratory of Neuroplasticity and Schizophrenia and Bipolar Disorders Program, McLean Hospital, Belmont, MA, USA.

CONTEXT: Bipolar disorder (BPD) is among the top 10 causes of disability worldwide. Recent findings on the etiology of the disease point to a disturbed mitochondrial energy metabolism in the brain of subjects with BPD. OBJECTIVE: To test whether gene transcripts for proteins of the mitochondrial respiratory chain have altered levels in glucose-deprived lymphocytes from patients with BPD. DESIGN: Microarrays were used to measure gene expression levels in fresh lymphocytes and in lymphocytes cultured for 5 days in regular or low-glucose medium. SETTING: Subjects with BPD were recruited through the Schizophrenia and Bipolar Disorders Program, McLean Hospital, Belmont, Mass. Controls were recruited through advertising. Patients A total of 21 patients with BPD (inpatients and outpatients) and 21 control subjects. Main Outcome Measure Expression levels for genes of proteins involved in mitochondrial respiration. RESULTS: We found an opposite molecular response of control and BPD lymphocytes to glucose deprivation. Whereas lymphocytes of normal controls responded to glucose deprivation with an up-regulation of nuclear transcripts for proteins of the electron transfer chain, subjects with BPD had a tendency to down-regulate these transcripts. CONCLUSIONS: The results suggest that the normal molecular adaptation to energy stress is deficient in lymphocytes from patients with BPD.

Published 8 May 2007 in Arch Gen Psychiatry, 64(5): 555-64.
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