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  Vol. 64 No. 5, May 2007 TABLE OF CONTENTS
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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

Alipi V. Naydenov, BS; Matthew L. MacDonald, BS; Dost Ongur, MD, PhD; Christine Konradi, PhD

Arch Gen Psychiatry. 2007;64(5):555-564.

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.


Author Affiliations: Laboratory of Neuroplasticity (Messrs Naydenov and MacDonald and Dr Konradi) and Schizophrenia and Bipolar Disorders Program (Dr Ongur), McLean Hospital, Belmont, Mass; and Department of Psychiatry, Harvard Medical School, Boston, Mass (Drs Ongur and Konradi).







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