title: Coenzyme Q10 effects on creatine kinase activity and mood in geriatric bipolar depression.
abstract: BACKGROUND
  Despite the prevalence, associated comorbidities, and functional consequences of bipolar depression (BPD), underlying disease mechanisms remain unclear. Published studies of individuals with bipolar disorder implicate abnormalities in cellular energy metabolism. This study tests the hypotheses that the forward rate constant (k(for)) of creatine kinase (CK) is altered in older adults with BPD and that CoEnzyme Q10 (CoQ10), known to have properties that enhance mitochondrial function, increases k(for) in elderly individuals with BPD treated with CoQ10 compared with untreated age- and sex-matched controls.
  
  
  METHODS
  Ten older adults (ages 55 and above) with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition [DSM IV]) bipolar disorder, current episode depressed and 8 older controls underwent two 4 Tesla (31)Phosphorus magnetic resonance spectroscopy ((31)PMRS) scans 8 weeks apart using a magnetization transfer (MT) acquisition scheme to calculate k(for). The BPD group was treated with open-label CoEnzyme Q10 400 mg/d titrated up by 400 mg/d every 2 weeks to a maximum of 1200 mg/d. The Montgomery Asberg Depression Rating Scale (MADRS) was used to measure depression symptom severity. Baseline k(for) and changes in k(for) were compared between individuals with BPD and controls, not receiving CoQ. Clinical ratings were compared across time and associated with k(for) changes using repeated measures linear regression.
  
  
  RESULTS
  The k(for) of CK was nonsignificantly lower for BPD than healthy controls at baseline (BPD mean (standard deviation [SD]) = 0.19 (0.02), control mean (SD) = 0.20 (0.02), Wilcoxon rank sum exact P = .40). The k(for) for both CoQ10-treated BPD and controls increased after 8 weeks (mean increase (SD) = 0.03 (0.04), Wilcoxon signed rank exact P = .01), with no significant difference in 8-week changes between groups (BPD mean change (SD) = 0.03 (0.03), control mean change (SD) = 0.03 (0.05), Wilcoxon rank sum exact P = .91). In an exploratory analysis, depression severity decreased with CoQ10 treatment in the group with BPD (F (3,7) = 4.87, P = .04) with significant reductions in the MADRS at weeks 2 (t (9) = -2.40, P = .04) and 4 (t (9) = -3.80, P = .004).
  
  
  CONCLUSIONS
  This study employing the novel MRS technique of MT did not demonstrate significance between group differences in the k(for) of CK but did observe a trend that would require confirmation in a larger study. An exploratory analysis suggested a reduction in depression symptom severity during treatment with high-dose CoEnzyme Q10 for older adults with BPD. Further studies exploring alterations of high-energy phosphate metabolites in geriatric BPD and efficacy studies of CoQ10 in a randomized controlled trial are both warranted.
authors.affiliation: Geriatric Psychiatry Research Program, McLean Hospital, Belmont, MA 02478, USA. bforester@mclean.harvard.edu
authors.forename: Brent P
authors.initials: BP
authors.lastname: Forester
authors.forename: Chun S
authors.initials: CS
authors.lastname: Zuo
authors.forename: Caitlin
authors.initials: C
authors.lastname: Ravichandran
authors.forename: David G
authors.initials: DG
authors.lastname: Harper
authors.forename: Fei
authors.initials: F
authors.lastname: Du
authors.forename: Susan
authors.initials: S
authors.lastname: Kim
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000368:Aged; D001714:Bipolar Disorder / Q000188:drug therapy / Q000201:enzymology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D016022:Case-Control Studies; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use
chemical_list: D014451:Ubiquinone; D003402:Creatine Kinase; C024989:coenzyme Q10