Brain GABA levels across psychiatric disorders: A systematic literature review and meta‐analysis of ¹H‐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.

Functional neuroanatomy in panic disorder: Status quo of the research

“…In our opinion it would be advisable to include psychiatric comparison groups. Schür et al[100] pointed out that the inhibitory GABA system is thought to be involved in the etiology of several psychiatric disorders. The authors therefore performed a meta-analysis including a total of 40 MRS studies in seven different psychiatric disorders ( n = 1.591).…”

“…Decreased GABAergic inhibition was reported in limbic, frontal, temporal, and respectively insular regions[15,98,99]. Unfortunately, the findings regarding the GABAergic system are partly inconsistent and may not be specific for PD[100]. …”

Molecular Neuroimaging in Posttraumatic Stress Disorder

“…Cr is often used as a denominator in signal ratio because Cr is in chemical equilibrium and comparatively unaffected by neurodegenerative processes [68]. GABA levels have also been examined using editing techniques such as MEGA-PRESS that allows for detecting brain GABA independently from other metabolites with overlapping resonances [69]. In most of the 1 H-MRS studies of PTSD, the ACC and temporal lobe structures including the hippocampus, which play an important role in the development and maintenance of PTSD symptoms, were investigated as regions of interest (ROIs) [7071727374].…”

“…In contrast, GABA levels were lowered in the insula [102], parieto-occipital cortex [96], and medial temporal cortex [96] of patients with PTSD than healthy controls. Although the number of studies was limited, a recent meta-analysis has reported no significant alterations in GABA levels related to PTSD [69]. …”

Immediate Decrease in γ-AminoButyric Acid after Caffeine Intake in Adolescents: a Preliminary MRS Study

“…in vivo GABA rate (3). To the best of our knowledge, no research has been conducted on the immediate response of the human brain, especially in adolescents, after caffeine intake.…”