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
Arch Gen Psychiatry. 2007 64 (5): 555-64

PMID: 17485607 · DOI:10.1001/archpsyc.64.5.555

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.

MeSH Terms (19)

Adult Bipolar Disorder Blood Glucose Cells, Cultured Down-Regulation Electron Transport Electron Transport Chain Complex Proteins Energy Metabolism Female Gene Expression Profiling Genes, Tumor Suppressor Glucose Humans Lymphocytes Male Middle Aged Mitochondria Nuclear Proteins Protein Array Analysis

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