Dorsolateral Prefrontal Cortex Glutamate/Gamma-Aminobutyric Acid (GABA) Alterations in Clinical High Risk and First-Episode Schizophrenia: A Preliminary 7-T Magnetic Resonance Spectroscopy Imaging Study

Converging lines of evidence suggest that an imbalance between excitation and inhibition is present in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia (SCZ). Gamma-aminobutyric-acid (GABA) and, to a lesser extent, glutamate (Glu) abnormalities were reported in the DLPFC of SCZ patients,...

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Published in:International journal of molecular sciences 2022-12, Vol.23 (24), p.15846
Main Authors: Mayeli, Ahmad, Sonnenschein, Susan F, Yushmanov, Victor E, Wilson, James D, Blazer, Annie, Foran, William, Perica, Maria, Calabro, Finnegan J, Luna, Beatriz, Hetherington, Hoby P, Sarpal, Deepak K, Ferrarelli, Fabio
Format: Article
Language:English
Subjects:
Abnormalities
Age
Asymmetry
Creatine
Dorsolateral Prefrontal Cortex
gamma-Aminobutyric Acid
Glutamic Acid
Hemispheric laterality
Humans
Illnesses
In vivo methods and tests
Magnetic Resonance Imaging
Magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy - methods
Mental disorders
Neuroimaging
Prefrontal cortex
Prefrontal Cortex - diagnostic imaging
Psychosis
Schizophrenia
Schizophrenia - diagnostic imaging
Spectrum analysis
Variance analysis
γ-Aminobutyric acid
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Summary:Converging lines of evidence suggest that an imbalance between excitation and inhibition is present in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia (SCZ). Gamma-aminobutyric-acid (GABA) and, to a lesser extent, glutamate (Glu) abnormalities were reported in the DLPFC of SCZ patients, especially on the right hemisphere, by post-mortem studies. However, in vivo evidence of GABA, Glu, and Glu/GABA DLPFC abnormalities, particularly on the right side and the early stages of illness, is limited. In this preliminary study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to investigate bilateral Glu/Creatine (Cre), GABA/Cre, and Glu/GABA in the DLPFC of sixteen first episode schizophrenia (FES), seventeen clinical high risk (CHR), and twenty-six healthy comparison (HC) subjects. FES and CHR had abnormal GABA/Cre and Glu/GABA in the right DLPFC (rDLPFC) compared with HC participants, while no differences were observed in the left DLPFC (lDLPFC) among the three groups. Furthermore, HC had higher Glu/GABA in rDLPFC compared to lDLPFC (R > L), whereas the opposite relationship (R < L) was observed in the DLPFC Glu/GABA of FES patients. Altogether, these findings indicate that GABA/Cre and Glu/GABA DLPFC alterations are present before illness manifestation and worsen in FES patients, thus representing a putative early pathophysiological biomarker for SCZ and related psychotic disorders.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms232415846