{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kiemes A"],"funding":["Wellcome Trust and the Royal Society","National Institute for Health Research (NIHR)","National Institute for Health and Care Research","Wellcome Trust","Maudsley Biomedical Research Centre"],"pagination":["pyaf078"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12874875"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(2)"],"pubmed_abstract":["<h4>Objective</h4>Preclinical evidence suggests that modulating neural excitation through administration of diazepam, a positive allosteric modulator of GABAA receptors, can prevent the emergence of behavioral and neurobiological alterations relevant to psychosis in adulthood.<h4>Design and participants</h4>Here, we examine 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 and 9 male) aged 18-35 were scanned twice using proton magnetic resonance spectroscopy to measure anterior cingulate cortex Glx (glutamate and glutamine) levels, once after a single dose of diazepam (5 mg) and once after placebo.<h4>Results</h4>Mixed-effects model analyses revealed that diazepam reduced anterior cingulate cortex Glx levels compared to placebo (t(20.8) = -2.14, P = .04). The effect of diazepam on Glx levels was greater in older individuals at clinical high risk for psychosis (t(12) = -4.36, P = .001).<h4>Conclusion</h4>These findings suggest that pharmacological modulation of GABAA receptors can alter Glx changes in and support a novel therapeutic mechanism of benefit for individuals at clinical high risk of psychosis."],"journal":["The international journal of neuropsychopharmacology"],"pubmed_title":["Diazepam modulates anterior cingulate glutamate levels in people at clinical high-risk for psychosis."],"pmcid":["PMC12874875"],"funding_grant_id":["202397/Z/16/Z","202397/Z/16/Z to G.M."],"pubmed_authors":["McGuire P","Livingston NR","Nettis MA","Stone JM","Modinos G","Grace AA","Casetta C","Knight S","Jelen L","Lythgoe DJ","De Micheli A","Reilly T","Fusar-Poli P","Williams SCR","Lukow PB","Kiemes A","Egerton A","Dima A","Spencer T","Davies C"],"additional_accession":[]},"is_claimable":false,"name":"Diazepam modulates anterior cingulate glutamate levels in people at clinical high-risk for psychosis.","description":"<h4>Objective</h4>Preclinical evidence suggests that modulating neural excitation through administration of diazepam, a positive allosteric modulator of GABAA receptors, can prevent the emergence of behavioral and neurobiological alterations relevant to psychosis in adulthood.<h4>Design and participants</h4>Here, we examine 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 and 9 male) aged 18-35 were scanned twice using proton magnetic resonance spectroscopy to measure anterior cingulate cortex Glx (glutamate and glutamine) levels, once after a single dose of diazepam (5 mg) and once after placebo.<h4>Results</h4>Mixed-effects model analyses revealed that diazepam reduced anterior cingulate cortex Glx levels compared to placebo (t(20.8) = -2.14, P = .04). The effect of diazepam on Glx levels was greater in older individuals at clinical high risk for psychosis (t(12) = -4.36, P = .001).<h4>Conclusion</h4>These findings suggest that pharmacological modulation of GABAA receptors can alter Glx changes in and support a novel therapeutic mechanism of benefit for individuals at clinical high risk of psychosis.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-06-30T03:28:18.002Z","creation":"2026-06-30T03:21:56.676Z"},"accession":"S-EPMC12874875","cross_references":{"pubmed":["41384764"],"doi":["10.1093/ijnp/pyaf078"]}}