Diazepam modulates anterior cingulate glutamate levels in people at clinical high-risk for psychosis:Diazepam and Glx in psychosis risk

Background<br/>Preclinical 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.<br/><br/>Methods<br/>Here, 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.<br/><br/>Results<br/>Mixed-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).<br/><br/>Conclusion<br/>These 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.<br/>