Mitochondrial Dysfunction in the Pathophysiology and Treatment of Bipolar Disorder

Summary

This study will examine whether mitochondrial function is impaired in patients with bipolar disorder. Mitrochondria are small organelles inside the cell that are responsible for energy production. Recent studies in animals and humans suggest that abnormalities of mitrochondria may be involved in bipolar depression. The study will also examine whether the food supplement Coenzyme Q10 (CoQ10) improves mitochondrial function and symptoms such as depressed mood, low energy, anxiety or slowness in thinking and movements in bipolar patients. CoQ10 has been used to increase cell energy production and as an antioxidant. It has had some benefit in patients with Parkinson's disease and migraine and in prolonging survival in patients with cancer and heart failure. Patients 18-65 years of age with bipolar disorder who are currently in a depressive episode of at least 4 weeks duration may be eligible for this study. The study has four phases, as follows: Phase I: Medication Withdrawal Patients taper off all psychotropic medications, usually over 1 to 2 weeks. Phase II: Baseline Evaluation After being off all medication for about 2 weeks, patients undergo the following procedures: * Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). The two procedures are performed in an MRI scanner. Both tests use a strong magnetic field and radio waves to obtain images that provide information on brain anatomy and chemistry. * Blood tests to assess mitochondrial function isolated from blood cells. * Skin biopsy for tests of mitochondria. A small sample of skin tissue 5 x 5 millimeters is surgically removed. Phase III: Administration of CoQ10 or Placebo Participants are randomly assigned to take either CoQ10 or placebo (an inactive look-alike substance) twice a day by mouth. While taking the study medication, patients have the following procedures periodically: * Rating scales for anxiety and depression and adverse events. * Check of vital signs. * Blood and urine sample collections. Phase IV: Study Completion At the end of the 8 weeks of treatment, patients have a physical examination and electrocardiogram, and the procedures in phase II are repeated. Participants may then receive short-term treatment (up to 12 weeks) with medications for bipolar depression, followed by referred to a community physician for long-term treatment. ...

Timeline

Start

2006-05

Primary completion

2009-05

Completion

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Publications

• Background Arias-Mendoza F. In vivo magnetic resonance spectroscopy in the evaluation of mitochondrial disorders. Mitochondrion. 2004 Sep;4(5-6):491-501. doi: 10.1016/j.mito.2004.07.034. Epub 2004 Sep 30.
• Background Baker SK, Tarnopolsky MA. Targeting cellular energy production in neurological disorders. Expert Opin Investig Drugs. 2003 Oct;12(10):1655-79. doi: 10.1517/13543784.12.10.1655.
• Background Bertolino A, Frye M, Callicott JH, Mattay VS, Rakow R, Shelton-Repella J, Post R, Weinberger DR. Neuronal pathology in the hippocampal area of patients with bipolar disorder: a study with proton magnetic resonance spectroscopic imaging. Biol Psychiatry. 2003 May 15;53(10):906-13. doi: 10.1016/s0006-3223(02)01911-x.

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