AUTHOR=Grent-’t-Jong Tineke , Gajwani Ruchika , Gross Joachim , Gumley Andrew I. , Lawrie Stephen M. , Schwannauer Matthias , Schultze-Lutter Frauke , Williams Stephen R. , Uhlhaas Peter J. 

TITLE=MR-Spectroscopy of GABA and Glutamate/Glutamine Concentrations in Auditory Cortex in Clinical High-Risk for Psychosis Individuals

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.859322

DOI=10.3389/fpsyt.2022.859322

ISSN=1664-0640

ABSTRACT=Psychosis involves changes in GABAergic and glutamatergic neurotransmission in auditory cortex that could be important for understanding sensory deficits and symptoms of psychosis. However, it is currently unclear whether such deficits are present in participants at clinical high-risk for psychosis (CHR-P) and whether they are associated with clinical outcomes. 
Magnetic Resonance Spectroscopy (MEGAPRESS, 1H-MRS at 3Tesla) was used to estimate GABA, glutamate, and glutamate-plus-glutamine (Glx) levels in auditory cortex in a large sample of CHR-P (n=99), CHR-N (high-risk for non-psychotic disorders, n=32), and 45 healthy controls. Examined were group differences in metabolite concentrations as well as relationships with clinical symptoms, general cognition, and 1-year follow-up clinical and general functioning in the CHR-P group. 
Results showed a marginal (p=0.039) main group effect only for Glx, but not for GABA and glutamate concentrations, and only in left, not right, auditory cortex. This effect did not survive multiple comparison correction, however. Exploratory post-hoc tests revealed that there were significantly lower Glx levels (p=0.029, uncorrected) in those at high-risk for psychotic disorders (CHR-Ps), compared to individuals at high-risk for non-psychotic disorders (CHR-Ns), but not relative to healthy controls (p=0.058, uncorrected). Correlational analyses revealed that Glx levels correlated with the severity of perceptual abnormalities and disorganized speech scores across CHR-Ns and CHR-Ps groups. In the CHR-P group, no evidence was found for Glx levels to be predictive of 1-year persistent of attenuated-psychotic symptoms.  
The current study did not  identify differences in GABA, glutamate and/or Glx levels in auditory cortex between CHR-Ps and controls. Glx concentrations tended to differ, however, between CHR-P and CHR-N, suggesting potential utility in differentiating psychotic from non-psychotic high-risk populations.