title: Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of (1) H-MRS studies.
abstract: The inhibitory gamma-aminobutyric acid (GABA) system is involved in the etiology of most psychiatric disorders, including schizophrenia, autism spectrum disorder (ASD) and major depressive disorder (MDD). It is therefore not surprising that proton magnetic resonance spectroscopy ((1) H-MRS) is increasingly used to investigate in vivo brain GABA levels. However, integration of the evidence for altered in vivo GABA levels across psychiatric disorders is lacking. We therefore systematically searched the clinical (1) H-MRS literature and performed a meta-analysis. A total of 40 studies (N = 1,591) in seven different psychiatric disorders were included in the meta-analysis: MDD (N = 437), schizophrenia (N = 517), ASD (N = 150), bipolar disorder (N = 129), panic disorder (N = 81), posttraumatic stress disorder (PTSD) (N = 104), and attention deficit/hyperactivity disorder (ADHD) (N = 173). Brain GABA levels were lower in ASD (standardized mean difference [SMD] = -0.74, P = 0.001) and in depressed MDD patients (SMD = -0.52, P = 0.005), but not in remitted MDD patients (SMD = -0.24, P = 0.310) compared with controls. In schizophrenia this finding did not reach statistical significance (SMD = -0.23, P = 0.089). No significant differences in GABA levels were found in bipolar disorder, panic disorder, PTSD, and ADHD compared with controls. In conclusion, this meta-analysis provided evidence for lower brain GABA levels in ASD and in depressed (but not remitted) MDD patients compared with healthy controls. Findings in schizophrenia were more equivocal. Even though future (1) H-MRS studies could greatly benefit from a longitudinal design and consensus on the preferred analytical approach, it is apparent that (1) H-MRS studies have great potential in advancing our understanding of the role of the GABA system in the pathogenesis of psychiatric disorders. Hum Brain Mapp 37:3337-3352, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Remmelt R
authors.initials: RR
authors.lastname: Schür
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Luc W R
authors.initials: LW
authors.lastname: Draisma
authors.affiliation: Department of Radiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Jannie P
authors.initials: JP
authors.lastname: Wijnen
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Marco P
authors.initials: MP
authors.lastname: Boks
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Martijn G J C
authors.initials: MG
authors.lastname: Koevoets
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Joëls
authors.affiliation: Department of Radiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Klomp
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
authors.forename: Christiaan H
authors.initials: CH
authors.lastname: Vinkers
mesh_terms: D001921:Brain / Q000378:metabolism*; D006801:Humans; D001523:Mental Disorders / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: 1H-MRS; ASD; GABA; MDD; meta-analysis; psychopathology