We propose to study and compare measures of brain energy metabolism in geriatric bipolar individuals and healthy older adults. We would also like to investigate changes in brain energy metabolites and in vivo creatine kinase (CK) enzymatic activity associated with CoQ10 administration in older bipolar individuals.

Hypotheses

1. At baseline, the forward rate constant (kfor) of CK enzymatic activity in the frontal lobe of older subjects with bipolar depression will be significantly decreased relative to that of age-matched healthy controls.
2. After 8 weeks of treatment, bipolar depression subjects will demonstrate an increase in the kfor of CK after 8 weeks of CoQ 10 treatment.
3. Increases in the CK forward rate constant (kfor) will correlate with improvement in subjects' mood state as assessed by the Montgomery Asberg Depression Rating Scale (MADRS).
4. Baseline measures of executive functioning and information processing speed (measured by performance on the Wisconsin Card Sorting Test (WCST), Trails A and B and Stroop tests) will be impaired in subjects with geriatric bipolar depression compared with healthy controls. These measures will improve with successful treatment with CoQ10 and correlate with increases in the CK forward rate constant (kfor).

Summary:

A review of literature suggests a distinct pattern of bioenergetic changes, possibly related to mitochondrial dysfunction and abnormal CK function, in older adults and in individuals with bipolar disorder. As opposed to rudimentary measurements of static metabolite concentrations, the novel use of MT-MRS in such individuals will offer insight into the enzyme kinetics of CK, specifically examining the rate at which ATP is formed from PCr. From previous investigations it would seem that the dietary-supplement, CoQ10, is able to improve the efficiency of mitochondrial function in subjects with altered bioenergetics. We propose to measure CK activity and PCr turnover rate before and after CoQ10 treatment, with the overall aim of understanding metabolic relationships between brain bioenergetic alterations and treatment with CoQ10 in geriatric bipolar depression.

Inclusion Criteria:

• 55 years or older
• Meet DSM-IV diagnostic criteria for Bipolar Disorder, Current Episode Depressed
• Montgomery Asberg Depression Rating Scale (MADRS) Score of >20
• If the MADRS score is <20 but >16, a diagnosis of bipolar disorder, current episode depressed, based on the Structured Clinical Interview of DSM IV TR (SCID) and Dr. Forester's initial interview would allow the subject to be included in the study.
• Young Mania Rating Scale (YMRS) Score of < 6
• If the YMRS score is >6 subjects can still be admitted if subjects do not meet clinical criteria for mania or hypomania at the time of screening
• Able to provide informed consent
• Must speak English
• Must be able to visit McLean Hospital for the screening visit and six study visits during the 8-week duration of the study
• Subjects may be taking other medications for bipolar depression including antidepressants, mood stabilizers and antipsychotic mediations prior to Co-Q10 therapy, but may not have any dosage adjustments of these medications in the week before Co-Q10 is added.

Exclusion Criteria:

• Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
• History of seizure disorder,
• History or current diagnosis of the following psychiatric illnesses: any organic mental disorder (including dementia), schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, unipolar major depressive disorder, patients with substance dependence disorders, including alcohol, active within the last 12 months.
• History of drug hypersensitivity or intolerance to Coenzyme Q10.
• Use of medications that are excluded in this study (barbiturates; however, the use of non-benzodiazepine sedative hypnotics (such as zolpidem (Ambien)) may be used as needed except within 12 hours of the MRI scan)
• Benzodiazepines may be used by subjects throughout the study as long as they are not taken within 12 hours of any MRI scan.
• Subjects diagnosed with a mitochondrial disorder.
• Subjects taking other putative mitochondrial enhancers (e.g., vitamin E, carnitine, creatine, Vitamin complex B, pramipexole) at the time of study entry.
• Any of the exclusion criteria mentioned in the MRI risks section below