Concerted elevations of cortical and striatal glutamate and GABA in antipsychotic-free individuals at clinical high-risk for psychosis.
Academic Article
Overview
abstract
While the literature on glutamate and γ-aminobutyric acid (GABA) levels as measured by proton magnetic spectroscopy (1H MRS) in psychosis is somewhat mixed, replicated findings from our group and others suggest that antipsychotic medication status is a critical factor in study outcomes, with cohorts of antipsychotic-free individuals generally showing elevated levels. The purpose of this study was to examine levels of glutamate and GABA in the medial prefrontal cortex (mPFC) and associative striatum (AST) in a multi-site sample of individuals at clinical high-risk for psychosis (CHR) who were antipsychotic-free for at least three weeks. The final study sample included 26 CHR individuals based on the Structured Interview for Psychosis-Risk Syndromes (SIPS) and 40 healthy control subjects. CHR subjects were excluded if they met criteria for bipolar I disorder or major depressive disorder with psychotic features. All subjects underwent 1H MRS scans to measure levels of Glx (a composite measure of glutamate and glutamine) and GABA in mPFC and AST. The results revealed elevations of both Glx and GABA in the mPFC and AST in CHR patients compared with control subjects (Glx at trend level in the mPFC). Within the CHR group, mPFC Glx was negatively correlated with positive and negative symptoms, uncorrected for multiple comparisons, and positively correlated with GABA. These results support the conclusion that antipsychotic medication status is a critical factor in the interpretation of ¹H MRS findings in psychosis spectrum disorders. Though our CHR group is only putatively prodromal, the data support the role of cortico-striatal circuit dysfunction in the pathophysiology of schizophrenia and add to a growing body of evidence for excitatory/inhibitory imbalance in the early stages of the illness.
