Coenzyme Q10 Effects on Creatine Kinase Activity and Mood in Geriatric Bipolar Depression

Abstract

Introduction 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 (kfor) 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 kfor 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 31Phosphorus magnetic resonance spectroscopy (31PMRS) scans 8 weeks apart using a magnetization transfer (MT) acquisition scheme to calculate kfor. 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 kfor and changes in kfor were compared between individuals with BPD and controls, not receiving CoQ. Clinical ratings were compared across time and associated with kfor changes using repeated measures linear regression. Results The kfor of CK was non-significantly 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 kfor 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 (F3,7 = 4.87, P = .04) with significant reductions in the MADRS at weeks 2 (t9 = −2.40, P = .04) and 4 (t9 = −3.80, P = .004). Conclusions This study employing the novel MRS technique of MT did not demonstrate significance between group differences in the kfor 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.

Chronic treatment with coenzyme Q10 reverses restraint stress-induced anhedonia and enhances brain mitochondrial respiratory chain and creatine kinase activities in rats

“…Reduction in CK activity may potentially impair energy homeostasis, leading to cell death (Aksenov et al, 2000). However, despite the fact that depression in humans and in animal models did not alter brain CK activity Forester et al, 2012), similar to the present results, chronic administration of some antidepressants, such as imipramine and paroxetine, increased CK activity in the rat brain (Santos et al, 2009;Réus et al, 2012). From these results, it can be hypothesized that enhancing mitochondrial function and CK activity may present an opportunity for the development of a potentially more efficient pharmacotherapy against depressive disorders.…”

“…Coenzyme Q10 (CoQ10), a lipid-soluble benzoquinone present in the phospholipid bilayers of mitochondria, is known to boost mitochondrial function. Accumulating evidence suggests a protective therapeutic role of CoQ10 in some neurodegenerative disorders, for example, Alzheimer's disease (Littarru and Tiano, 2007), Parkinson's disease (Hargreaves et al, 2008), epilepsy (Tawfik, 2011), and major depression (Forester et al, 2012). CoQ10 is a ubiquitous compound, found in the highest concentrations in tissues with high energy turnover such as the brain and heart (Beal, 2002).…”

A Placebo-Controlled Trial of Acetyl-L-Carnitine and α-Lipoic Acid in the Treatment of Bipolar Depression

“…34 Therefore, further investigation into the exact mechanism(s) of action of NAC is warranted. Recently, an open-label study of CoQ10 in geriatric patients with bipolar depression demonstrated antidepressant effects early in treatment, which dissipated by the end of the 8-week study, 45 supporting further investigation in larger controlled trials.…”

Antidepressant Effects of Open Label Treatment With Coenzyme Q10 in Geriatric Bipolar Depression

“…Following IRB approval, subjects were recruited to participate in two studies investigating the bioenergetic effects of CoQ10 utilizing a 31 P-MRS protocol at 4 Tesla (T) 16 (Forester, unpublished). Subjects met DSM-IV TR criteria for Bipolar Disorder, Type I or II, current episode depressed, and were excluded with any previous or current co-morbid Axis I disorder, unstable medical illness, untreated thyroid dysfunction, a history of substance abuse within the past year, Young Mania Rating Scale (YMRS) score of > 6, or Montgomery Asberg Depression Rating Scale (MADRS) < 18.…”