P W Chiu1, Simon S Y Lui2, Karen S Y Hung3, Raymond C K Chan4, Queenie Chan5, P C Sham6, Eric F C Cheung3, Henry K F Mak7. 1. Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China. 2. Castle Peak Hospital, Hong Kong, China; Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China. 3. Castle Peak Hospital, Hong Kong, China. 4. Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China; Department of Psychiatry, The University of Hong Kong, Hong Kong, China. 5. Philips Healthcare Hong Kong, Hong Kong, China. 6. State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China; Department of Psychiatry, The University of Hong Kong, Hong Kong, China. 7. Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China; Alzheimer's Disease Research Network, The University of Hong Kong, Hong Kong, China. Electronic address: makkf@hku.hk.
Abstract
BACKGROUND: Gamma-aminobutyric acid (GABA) dysfunction and its consequent imbalance are implicated in the pathophysiology of schizophrenia. Reduced GABA production would lead to a disinhibition of glutamatergic neurons and subsequently cause a disruption of the modulation between GABAergic interneurons and glutamatergic neurons. In this study, levels of GABA, Glx (summation of glutamate and glutamine), and other metabolites in the anterior cingulate cortex were measured and compared between first-episode schizophrenia subjects and healthy controls (HC). Diagnostic potential of GABA and Glx as upstream biomarkers for schizophrenia was explored. METHODS: Nineteen first-episode schizophrenia subjects and fourteen HC participated in this study. Severity of clinical symptoms of patients was measured with Positive and Negative Syndrome Scale (PANSS). Metabolites were measured using proton magnetic resonance spectroscopy, and quantified using internal water as reference. RESULTS: First-episode schizophrenia subjects revealed reduced GABA and myo-inositol (mI), and increased Glx and choline (Cho), compared to HC. No significant correlation was found between metabolite levels and PANSS scores. Receiver operator characteristics analyses showed Glx had higher sensitivity and specificity (84.2%, 92.9%) compared to GABA (73.7%, 64.3%) for differentiating schizophrenia patients from HC. Combined model of both GABA and Glx revealed the best sensitivity and specificity (89.5%, 100%). CONCLUSION: This study simultaneously showed reduction in GABA and elevation in Glx in first-episode schizophrenia subjects, and this might provide insights on explaining the disruption of modulation between GABAergic interneurons and glutamatergic neurons. Elevated Cho might indicate increased membrane turnover; whereas reduced mI might reflect dysfunction of the signal transduction pathway. In vivo Glx and GABA revealed their diagnostic potential for schizophrenia.
BACKGROUND:Gamma-aminobutyric acid (GABA) dysfunction and its consequent imbalance are implicated in the pathophysiology of schizophrenia. Reduced GABA production would lead to a disinhibition of glutamatergic neurons and subsequently cause a disruption of the modulation between GABAergic interneurons and glutamatergic neurons. In this study, levels of GABA, Glx (summation of glutamate and glutamine), and other metabolites in the anterior cingulate cortex were measured and compared between first-episode schizophrenia subjects and healthy controls (HC). Diagnostic potential of GABA and Glx as upstream biomarkers for schizophrenia was explored. METHODS: Nineteen first-episode schizophrenia subjects and fourteen HC participated in this study. Severity of clinical symptoms of patients was measured with Positive and Negative Syndrome Scale (PANSS). Metabolites were measured using proton magnetic resonance spectroscopy, and quantified using internal water as reference. RESULTS: First-episode schizophrenia subjects revealed reduced GABA and myo-inositol (mI), and increased Glx and choline (Cho), compared to HC. No significant correlation was found between metabolite levels and PANSS scores. Receiver operator characteristics analyses showed Glx had higher sensitivity and specificity (84.2%, 92.9%) compared to GABA (73.7%, 64.3%) for differentiating schizophreniapatients from HC. Combined model of both GABA and Glx revealed the best sensitivity and specificity (89.5%, 100%). CONCLUSION: This study simultaneously showed reduction in GABA and elevation in Glx in first-episode schizophrenia subjects, and this might provide insights on explaining the disruption of modulation between GABAergic interneurons and glutamatergic neurons. Elevated Cho might indicate increased membrane turnover; whereas reduced mI might reflect dysfunction of the signal transduction pathway. In vivo Glx and GABA revealed their diagnostic potential for schizophrenia.
Authors: Marquis P Vawter; Abdul Rezzak Hamzeh; Edgar Muradyan; Olivier Civelli; Geoffrey W Abbott; Amal Alachkar Journal: Mol Neuropsychiatry Date: 2019-08-08
Authors: Lihong Tang; Yibo Zhao; Yudu Li; Rong Guo; Bryan Clifford; Georges El Fakhri; Chao Ma; Zhi-Pei Liang; Jie Luo Journal: Magn Reson Med Date: 2020-07-29 Impact factor: 4.668
Authors: Jacek Baj; Elżbieta Sitarz; Alicja Forma; Katarzyna Wróblewska; Hanna Karakuła-Juchnowicz Journal: Int J Mol Sci Date: 2020-02-21 Impact factor: 5.923