Neuroimaging studies of GABA in schizophrenia: a systematic review with meta-analysis

Journal article

BackgroundPreclinical evidence suggests that modulating neural excitation through diazepam administration, a positive allosteric modulator of GABAA receptors, can prevent the emergence of behavioral and neurobiological alterations relevant to psychosis in adulthood.MethodsHere, we examined this neurochemical mechanism in individuals at clinical high-risk for psychosis in a randomized, double-blind, placebo-controlled crossover study. Twenty-four individuals (15 female, 9 male) aged 18-35 were scanned twice using proton magnetic resonance spectroscopy (1H-MRS) to measure anterior cingulate cortex Glx (glutamate and glutamine) levels, once after a single dose of diazepam (5 mg), and once after placebo.ResultsMixed-effects model analyses revealed that diazepam reduced anterior cingulate cortex Glx levels compared to placebo (t(20.8) = -2.14, p = 0.04). The effect of diazepam on Glx levels was greater in older individuals at clinical high-risk for psychosis (t(12) = -4.36, p = 0.001).ConclusionThese findings suggest that pharmacological modulation of GABAA receptors can alter Glx changes in clinical high-risk for psychosis and support a novel therapeutic mechanism of benefit for individuals at clinical high-risk of psychosis.

Authors: Egerton, A; Modinos, G; Ferrera, D; McGuire, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: Translational Psychiatry
• Volume: 7
• Issue: 6
• Pages: e1147-e1147
• Publication date: 2017-06-06
• DOI: 10.1038/tp.2017.124
• EISSN: 2158-3188
• ISSN: 2158-3188
• Language: English
• Keywords: Neuroscience; Neuroimaging; Meta-analysis; Cognition; Schizophrenia (object-oriented programming); Postmortem studies; Psychosis; Positron emission tomography; Striatum; Psychiatry; Medicine; Internal medicine; Prefrontal cortex; GABAergic; Receptor; Psychology