title: Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder.
abstract: Creatine monohydrate (creatine) augmentation has the potential to accelerate the clinical responses to and enhance the overall efficacy of selective serotonin reuptake inhibitor treatment in women with major depressive disorder (MDD). Although it has been suggested that creatine augmentation may involve the restoration of brain energy metabolism, the mechanisms underlying its antidepressant efficacy are unknown.
  
  
  
  In a randomized, double-blind, placebo-controlled trial, 52 women with MDD were assigned to receive either creatine augmentation or placebo augmentation of escitalopram; 34 subjects participated in multimodal neuroimaging assessments at baseline and week 8. Age-matched healthy women (n = 39) were also assessed twice at the same intervals. Metabolic and network outcomes were measured for changes in prefrontal N-acetylaspartate and changes in rich club hub connections of the structural brain network using proton magnetic resonance spectroscopy and diffusion tensor imaging, respectively.
  
  
  
  We found MDD-related metabolic and network dysfunction at baseline. Improvement in depressive symptoms was greater in patients receiving creatine augmentation relative to placebo augmentation. After 8 weeks of treatment, prefrontal N-acetylaspartate levels increased significantly in the creatine augmentation group compared with the placebo augmentation group. Increment in rich club hub connections was also greater in the creatine augmentation group than in the placebo augmentation group.
  
  
  
  N-acetylaspartate levels and rich club connections increased after creatine augmentation of selective serotonin reuptake inhibitor treatment. Effects of creatine administration on brain energy metabolism and network organization may partly underlie its efficacy in treating women with MDD.
authors.affiliation: Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea.
authors.forename: Sujung
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea.
authors.forename: Jieun E
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Soonchunhyang University College of Medicine, Seoul, South Korea.
authors.forename: Jaeuk
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, South Korea.
authors.forename: Tae-Suk
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea.
authors.forename: Eun
authors.initials: E
authors.lastname: Namgung
authors.affiliation: Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea.
authors.forename: Soonhyun
authors.initials: S
authors.lastname: Ban
authors.affiliation: Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea.
authors.forename: Subin
authors.initials: S
authors.lastname: Oh
authors.affiliation: Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea.
authors.forename: Jeongwon
authors.initials: J
authors.lastname: Yang
authors.affiliation: Brain Institute and Department of Psychiatry, University of Utah, Salt Lake City, Utah.
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
authors.affiliation: Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea; Brain Institute and Department of Psychiatry, University of Utah, Salt Lake City, Utah. Electronic address: inkylyoo@ewha.ac.kr.
authors.forename: In Kyoon
authors.initials: IK
authors.lastname: Lyoo
mesh_terms: D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D016022:Case-Control Studies; D015283:Citalopram / Q000627:therapeutic use; D003401:Creatine / Q000494:pharmacology* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D056324:Diffusion Tensor Imaging; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008875:Middle Aged; D009434:Neural Pathways / Q000502:physiology; D017397:Prefrontal Cortex / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D055815:Young Adult
chemical_list: D015283:Citalopram; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine
keywords: Antidepressant; Brain bioenergetics; Creatine monohydrate; Major depressive disorder; Network organization; Selective serotonin reuptake inhibitor