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.