Differences in lymphocyte electron transport gene expression levels between subjects with bipolar disorder and normal controls in response to glucose deprivation stress.
BACKGROUND
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.


METHODS
Microarrays were used to measure gene expression levels in fresh lymphocytes and in lymphocytes cultured for 5 days in regular or low-glucose medium.


METHODS
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.
Naydenov
Alipi V
AV
Laboratory of Neuroplasticity and Schizophrenia and Bipolar Disorders Program, McLean Hospital, Belmont, MA, USA.
MacDonald
Matthew L
ML
Ongur
Dost
D
Konradi
Christine
C
D000328:Adult; D001714:Bipolar Disorder / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D004579:Electron Transport / Q000187:drug effects / Q000235:genetics; D045222:Electron Transport Chain Complex Proteins / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics* / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins; D040081:Protein Array Analysis
D001786:Blood Glucose; D045222:Electron Transport Chain Complex Proteins; C403503:FAM107A protein, human; D009687:Nuclear Proteins; D005947:Glucose