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 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- World Health Organization
- Gobierno
- National Institutes of Health
- Gobierno
- National Institute of Mental Health
- Gobierno
- National Institute on Drug Abuse
- Gobierno
- National Center for Advancing Translational Sciences
- Gobierno
- NIMH NIH HHS
- Gobierno
- NIDA NIH HHS
- Gobierno
- NCATS NIH HHS
- Subvenciones
- 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)
Según 8 financiadores declarados.
Publicación
- Publicado
- 2016-02-23 · Amino Acids · vol. 48 · número 8 · págs. 1941–1954
- Editorial
- Springer Science+Business Media
- Citado
- 82 citas · más que el 96% de estudios similares · 5.9× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 99 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY
- Áreas de investigación
- Advanced MRI Techniques and Applications · Functional Brain Connectivity Studies · Treatment of Major Depression
- Palabras clave
- 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 autores
- Douglas G. Kondo🇺🇸 · autor de correspondenciaUniversity of Utah
- Lauren N. Forrest🇺🇸Allen Institute for Brain Science
- Xianfeng Shi🇺🇸University of Utah
- Young-Hoon Sung🇺🇸University of Utah
- Tracy Hellem🇺🇸Allen Institute for Brain Science
- Rebekah S. Huber🇺🇸Allen Institute for Brain Science
- Perry Franklin Renshaw🇺🇸University of Utah
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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