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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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15846 |
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| author | Ahmad Mayeli Susan F. Sonnenschein Victor E. Yushmanov James D. Wilson Annie Blazer William Foran Maria Perica Finnegan J. Calabro Beatriz Luna Hoby P. Hetherington Deepak K. Sarpal Fabio Ferrarelli |
| author_facet | Ahmad Mayeli Susan F. Sonnenschein Victor E. Yushmanov James D. Wilson Annie Blazer William Foran Maria Perica Finnegan J. Calabro Beatriz Luna Hoby P. Hetherington Deepak K. Sarpal Fabio Ferrarelli |
| author_sort | Ahmad Mayeli |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T16:19:31Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:19:31Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-362f41112ee241e1999a60798f16386e2023-11-24T15:29:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241584610.3390/ijms232415846Dorsolateral Prefrontal Cortex Glutamate/Gamma-Aminobutyric Acid (GABA) Alterations in Clinical High Risk and First-Episode Schizophrenia: A Preliminary 7-T Magnetic Resonance Spectroscopy Imaging StudyAhmad Mayeli0Susan F. Sonnenschein1Victor E. Yushmanov2James D. Wilson3Annie Blazer4William Foran5Maria Perica6Finnegan J. Calabro7Beatriz Luna8Hoby P. Hetherington9Deepak K. Sarpal10Fabio Ferrarelli11Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Radiology, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Radiology, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USAConverging 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.https://www.mdpi.com/1422-0067/23/24/15846dorsolateral prefrontal cortexDLPFCfirst episode schizophreniagamma-aminobutyric acidGABAclinical high risk for psychosis |
| spellingShingle | Ahmad Mayeli Susan F. Sonnenschein Victor E. Yushmanov James D. Wilson Annie Blazer William Foran Maria Perica Finnegan J. Calabro Beatriz Luna Hoby P. Hetherington Deepak K. Sarpal Fabio Ferrarelli 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 International Journal of Molecular Sciences dorsolateral prefrontal cortex DLPFC first episode schizophrenia gamma-aminobutyric acid GABA clinical high risk for psychosis |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | dorsolateral prefrontal cortex DLPFC first episode schizophrenia gamma-aminobutyric acid GABA clinical high risk for psychosis |
| url | https://www.mdpi.com/1422-0067/23/24/15846 |
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