Differences in Lymphocyte Electron Transport Gene Expression Levels Between Subjects With Bipolar Disorder and Normal Controls in Response to Glucose Deprivation Stress

Abstract

<h3>Context</h3> 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. <h3>Objective</h3> To test whether gene transcripts for proteins of the mitochondrial respiratory chain have altered levels in glucose-deprived lymphocytes from patients with BPD. <h3>Design</h3> Microarrays were used to measure gene expression levels in fresh lymphocytes and in lymphocytes cultured for 5 days in regular or low-glucose medium. <h3>Setting</h3> Subjects with BPD were recruited through the Schizophrenia and Bipolar Disorders Program, McLean Hospital, Belmont, Mass. Controls were recruited through advertising. <h3>Patients</h3> A total of 21 patients with BPD (inpatients and outpatients) and 21 control subjects. <h3>Main Outcome Measure</h3> Expression levels for genes of proteins involved in mitochondrial respiration. <h3>Results</h3> 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. <h3>Conclusions</h3> The results suggest that the normal molecular adaptation to energy stress is deficient in lymphocytes from patients with BPD.