Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression
Kondo DG, Forrest LN, Shi X, Sung YH, Hellem TL, Huber RS, Renshaw PF
Amino acids · 56 citations
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- World Health Organization
- Government
- National Institutes of Health
- Government
- National Institute of Mental Health
- Government
- National Institute on Drug Abuse
- Government
- National Center for Advancing Translational Sciences
- Government
- NIMH NIH HHS
- Government
- NIDA NIH HHS
- Government
- NCATS NIH HHS
- Grants
- National Institute on Drug Abuse (K05DA031247); National Institute of Mental Health (R33MH096858); National Center for Advancing Translational Sciences (UL1-TR001067); National Institute of Mental Health (R21 MH096858); National Institute of Mental Health (5R21MH096858)
Based on 8 listed funder(s).
Publication
- Published
- 2016-02-23 · Amino Acids · vol. 48 · issue 8 · pp. 1941–1954
- Publisher
- Springer Science+Business Media
- Cited
- 82 citations · more than 96% of similar papers · 5.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 99 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Advanced MRI Techniques and Applications · Functional Brain Connectivity Studies · Treatment of Major Depression
- Keywords
- Phosphocreatine, Major depressive disorder, Creatine, Internal medicine, Placebo, Frontal lobe, Psychology, Depression (economics), Antidepressant, Medicine, Endocrinology, Psychiatry, Mood, Hippocampus, Pathology
- MeSH
- brain, humans, creatinine, energy metabolism, drug resistance, adolescent, adult, female, neuroimaging, selective serotonin reuptake inhibitors, major depressive disorder
7 authors
From US
- Douglas G. Kondo · correspondingUniversity of Utah
- Lauren N. ForrestAllen Institute for Brain Science
- Xianfeng ShiUniversity of Utah
- Young-Hoon SungUniversity of Utah
- Tracy HellemAllen Institute for Brain Science
- Rebekah S. HuberAllen Institute for Brain Science
Abstract
Major depressive disorder (MDD) often begins during adolescence and is projected to become the leading cause of global disease burden by the year 2030. Yet, approximately 40 % of depressed adolescents fail to respond to standard antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI). Converging evidence suggests that depression is related to brain mitochondrial dysfunction. Our previous studies of MDD in adult and adolescent females suggest that augmentation of SSRI pharmacotherapy with creatine monohydrate (CM) may improve MDD outcomes. Neuroimaging with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) can measure the high-energy phosphorus metabolites in vivo that reflect mitochondrial function. These include phosphocreatine (PCr), a substrate for the creatine kinase reaction that produces adenosine triphosphate. As part of the National Institute of Mental Health's experimental medicine initiative, we conducted a placebo-controlled dose-ranging study of adjunctive CM for adolescent females with SSRI-resistant MDD. Participants were randomized to receive placebo or CM 2, 4 or 10 g daily for 8 weeks. Pre- and post-treatment (31)P-MRS scans were used to measure frontal lobe PCr, to assess CM's target engagement with cerebral energy metabolism. Mean frontal lobe PCr increased by 4.6, 4.1 and 9.1 % in the 2, 4 and 10 g groups, respectively; in the placebo group, PCr fell by 0.7 %. There was no group difference in adverse events, weight gain or serum creatinine. Regression analysis of PCr and depression scores across the entire sample showed that frontal lobe PCr was inversely correlated with depression scores (p = 0.02). These results suggest that CM achieves target engagement with brain bioenergetics and that the target is correlated with a clinical signal. Further study of CM as a treatment for adolescent females with SSRI-resistant MDD is warranted.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
Community trust
Loading…
How much do you trust this study's findings?
Comments
Sign in to rate, comment on or flag this study.Sign inSomething wrong here?
Flag this study if its information, labels or funding look wrong. An editor reviews every flag.
Sign in to rate, comment on or flag this study.Sign inEducational information about published research. Not medical advice, and not a recommendation to start or stop anything.