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Differences in lymphocyte electron transport gene expression levels between subjects with bipolar disorder and normal
Alipi V Naydenov1, Matthew L MacDonald, Dost Ongur
1Laboratory 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.
