Reduced cortical GABA and glutamate in high schizotypy

Petya Kozhuharova,Andreea O Diaconescu,Paul Allen

doi:10.1007/s00213-021-05867-y

Petya Kozhuharova, Andreea O Diaconescu + Show 1 more

Open Access

https://doi.org/10.1007/s00213-021-05867-y

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Abstract

RationaleAbnormal 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.ObjectivesWe 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.MethodsWe 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.ResultsCompared to individuals with low schizotypy traits, high schizotypy individuals showed lower cortical prefrontal GABA (F (1,38) = 5.18, p = 0.03, η2 = 0.09) and glutamate metabolite levels (F (1, 49) = 6.25, p = 0.02, η2 = 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).ConclusionsThese 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.

Highlights

There is a growing consensus that psychosis exists on a continuum ranging from subclinical psychotic-like experiences in the general population to full-blown psychotic symptoms in clinical samples (Linscott and Van Os 2013)
Using 1H-magnetic resonance spectroscopy (MRS), the present study found that relative to the low schizotypy group (LS) group, the high schizotypy group (HS) group had significantly lower mPFC gamma-aminobutyric acid (GABA) and glutamate metabolite concentrations
These results are in line with previous studies in schizophrenia populations which show that patients have lower mPFC GABA levels compared to healthy controls (Marsman et al 2013; Öngür et al 2010; Zhilei et al 2015; Rowland et al 2013)

Summary

Introduction

There is a growing consensus that psychosis exists on a continuum ranging from subclinical psychotic-like experiences in the general population to full-blown psychotic symptoms in clinical samples (Linscott and Van Os 2013). Investigating schizotypal traits in non-clinical samples may provide information about neurobiological alterations underlying psychosis-like symptoms (phenotype) in the absence of confounding factors such as antipsychotic medication. Schizotypal personality traits are qualitatively similar, but less severe than the symptoms seen in patients with schizophrenia. Relative to patients with schizophrenia, individuals scoring high on schizotypy trait measures show similar,. Fewer studies have investigated if there are neurochemical alterations in schizotypy populations similar to those reported in schizophrenia (Egerton et al 2017) and predicted by animal models to influence psychosis symptomatology (Du and Grace 2013)

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