A Longitudinal Assessment of Anterior Cingulate Cortex Gamma-aminobutyric Acid in Antipsychotic Medication-naïve First Episode Psychosis Patients

Abstract

Background and Hypothesis Converging evidence from animal and human studies has implicated gamma-aminobutyric acid (GABA)-ergic dysfunction in the pathophysiology of psychosis spectrum disorders. However, little is known about GABA’s role in the early illness stages. Based on prior research, we hypothesized that GABA levels would already be altered in first episode psychosis patients (FEP), and that they would be associated with patients’ cognitive function and response to treatment. Study Design We used magnetic resonance spectroscopy with a MEGA-PRESS sequence to quantify GABA in the dorsal anterior cingulate cortex (ACC) at baseline and over the course of antipsychotic treatment with risperidone. We compared GABA levels between 79 medication-naïve FEP and 113 healthy controls (HC) longitudinally over a period of 16 weeks and examined their relationships to cognition and treatment response. Study Results We found significantly lower GABA levels in FEP compared to HC at all 3 time points (baseline, 6 weeks, 16 weeks), but did not observe a significant main effect of time or an interaction of group by time. We found no significant correlations between GABA and cognitive scores. Baseline GABA levels of patients considered treatment nonresponders significantly differed from HC, whereas responders did not. Conclusions Our findings suggest that GABA dysfunction in the ACC may be an important feature of the core pathophysiology of psychosis. This dysfunction does not appear to be attenuated by conventional antipsychotic treatment, though baseline levels may be indicative of clinical prognosis in FEP.