Reduced cortical GABA and glutamate in high schizotypy

Rationale Abnormal functioning of the inhibitory gamma-aminobutyric acid (GABA) and excitatory (glutamate) systems is proposed to play a role in the development of schizophrenia spectrum disorder. Although results are mixed, previous 1H-magnetic resonance spectroscopy (MRS) studies in schizophrenia and clinical high-risk samples report these metabolites are altered in comparison to healthy controls. Currently, however, there are few studies of these metabolites in schizotypy samples, a personality dimension associated with the experience of schizophrenia and psychosis-like symptoms. Objectives We investigated if GABA and glutamate metabolite concentrations are altered in people with high schizotypy. We also explored the relationship between resilience to stress, GABA metabolite concentrations and schizotypy. Methods We used MRS to examine GABA and glutamate levels in the medial prefrontal cortex in people with low and high schizotypy traits as assessed with the Schizotypal Personality Questionnaire. Resilience to stress was assessed using the Connor-Davidson Resilience Scale. Results Compared to individuals with low schizotypy traits, high schizotypy individuals showed lower cortical prefrontal GABA (F (1,38) = 5.18, p = 0.03, eta(2) = 0.09) and glutamate metabolite levels (F (1, 49) = 6.25, p = 0.02, eta(2) = 0.02). Furthermore, participants with high GABA and high resilience levels were significantly more likely to be in the low schizotypy group than participants with low GABA and high resilience or high GABA and low resilience (95% CI 1.07-1.34, p < .001). Conclusions These findings demonstrate that subclinical schizotypal traits are associated with abnormal functioning of both inhibitory and excitatory systems and suggest that these transmitters are implicated in a personality trait believed to be on a continuum with psychosis.