Effect of Electroconvulsive Therapy on Medial Prefrontal γ-Aminobutyric Acid among Schizophrenia Patients: A Proton Magnetic Resonance Spectroscopy Study

Mengqing Xia; Junjie Wang; Jianhua Sheng; Yingying Tang; Chunyan Li; Kelvin Lim; Bin He; Chunbo Li; Yifeng Xu; Jijun Wang

doi:10.1097/YCT.0000000000000507

Effect of Electroconvulsive Therapy on Medial Prefrontal γ-Aminobutyric Acid among Schizophrenia Patients: A Proton Magnetic Resonance Spectroscopy Study

Mengqing Xia, Junjie Wang, Jianhua Sheng, Yingying Tang, Chunyan Li, Kelvin Lim, Bin He, Chunbo Li, Yifeng Xu, Jijun Wang

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Objective Electroconvulsive therapy ECT has often been applied to augment antipsychotics for schizophrenia patients. However, the underpinning mechanism is still unclear. Previous studies of major depressive disorder reported an increase in γ-aminobutyric acid GABA after ECT. The present study investigated the effects of ECT on medial prefrontal GABA in schizophrenia using a proton magnetic resonance spectroscopy. Methods Inpatients fulfilling the diagnostic criteria for schizophrenia Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were assigned to 2 groups, ECT group n = 14 receiving ECT plus antipsychotic drugs APD and drug group n = 17 only receiving antipsychotic drugs. Medial prefrontal GABA+/Cr concentrations of all patients were measured with magnetic resonance spectroscopy at baseline and after 4-week treatment. Sex- and age-matched healthy comparisons n = 19 were scanned at baseline. Results γ-Aminobutyric acid level did not show a significant difference among 3 groups. However, when 2 patient groups were combined, their GABA level was significantly lower than that in healthy comparisons group. For schizophrenia patients, repeated measures analysis of variance revealed that both the group effect and group × time interaction were insignificant, but the time effect of baseline versus after treatment was significant. Exploratory post hoc paired t test found a significant increase of GABA only in ECT group, but not in drug group. No correlation was found between GABA change and clinical symptom improvement in either group. Conclusions γ-Aminobutyric acid level in the medial prefrontal lobe was reduced in schizophrenia patients. An increase in GABA concentration in the medial prefrontal cortex is more significantly associated with ECT plus antipsychotics than antipsychotics alone, possibly supporting the hypothesis of ECT augmentation for GABA mediated neural inhibition.

Original language	English (US)
Pages (from-to)	227-232
Number of pages	6
Journal	Journal of ECT
Volume	34
Issue number	4
DOIs	https://doi.org/10.1097/YCT.0000000000000507
State	Published - Dec 1 2018
Externally published	Yes

Bibliographical note

Funding Information:
From the *Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; Departments of †Psychiatry and ‡Biomedical Engineering, University of Minnesota, Minneapolis, MN; §CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Science; ||Brain Science and Technology Research Center, and ¶Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China. Received for publication July 21, 2017; accepted March 29, 2018. Reprints: Jijun Wang, PhD, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Rd, Shanghai 200030, China (e‐mail: jijunwang27@163.com); or Yingying Tang, PhD, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Rd, Shanghai 200030, China (e‐mail: yytang0522@gmail.com). This work was supported by grants from Ministry of Science and Technology of the People’s Republic of China (2016YFC1306803), National Natural Science Foundation of China (81671329 and 81671332), Program of Shanghai Academic/Technology Research Leader (16XD1402400), Shanghai Science and Technology Committee (16JC1420200 and 17ZR1424700), National Key Clinical Disciplines at Shanghai Mental Health Center (OMA-MH, 2011-873), Shanghai Key Laboratory of Psychotic Disorders (13dz2260500), Shanghai Jiao Tong University Foundation (14JCRY04 and YG2014MS40), SHSMU-ION Research Center for Brain Disorders (2015NKX001, 15ZH2015, and W35XT), Medicine Engineering Intersection Program of Shanghai Jiaotong University (YG2015ZD12), and Shanghai Hospital Development Center (16CR2015A and 16CR3017A). The authors have no conflicts of interest or financial disclosures to report. M.X. and J.W. equally contributed to this work. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000507 Conclusions: γ-Aminobutyric acid level in the medial prefrontal lobe was reduced in schizophrenia patients. An increase in GABA concentration in the medial prefrontal cortex is more significantly associated with ECT plus antipsychotics than antipsychotics alone, possibly supporting the hypothesis of ECT augmentation for GABA mediated neural inhibition.

Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved 2017.

Keywords

electroconvulsive therapy
proton magnetic resonance spectroscopy
schizophrenia
γ-aminobutyric acid

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title = "Effect of Electroconvulsive Therapy on Medial Prefrontal γ-Aminobutyric Acid among Schizophrenia Patients: A Proton Magnetic Resonance Spectroscopy Study",

abstract = "Objective Electroconvulsive therapy ECT has often been applied to augment antipsychotics for schizophrenia patients. However, the underpinning mechanism is still unclear. Previous studies of major depressive disorder reported an increase in γ-aminobutyric acid GABA after ECT. The present study investigated the effects of ECT on medial prefrontal GABA in schizophrenia using a proton magnetic resonance spectroscopy. Methods Inpatients fulfilling the diagnostic criteria for schizophrenia Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were assigned to 2 groups, ECT group n = 14 receiving ECT plus antipsychotic drugs APD and drug group n = 17 only receiving antipsychotic drugs. Medial prefrontal GABA+/Cr concentrations of all patients were measured with magnetic resonance spectroscopy at baseline and after 4-week treatment. Sex- and age-matched healthy comparisons n = 19 were scanned at baseline. Results γ-Aminobutyric acid level did not show a significant difference among 3 groups. However, when 2 patient groups were combined, their GABA level was significantly lower than that in healthy comparisons group. For schizophrenia patients, repeated measures analysis of variance revealed that both the group effect and group × time interaction were insignificant, but the time effect of baseline versus after treatment was significant. Exploratory post hoc paired t test found a significant increase of GABA only in ECT group, but not in drug group. No correlation was found between GABA change and clinical symptom improvement in either group. Conclusions γ-Aminobutyric acid level in the medial prefrontal lobe was reduced in schizophrenia patients. An increase in GABA concentration in the medial prefrontal cortex is more significantly associated with ECT plus antipsychotics than antipsychotics alone, possibly supporting the hypothesis of ECT augmentation for GABA mediated neural inhibition.",

keywords = "electroconvulsive therapy, proton magnetic resonance spectroscopy, schizophrenia, γ-aminobutyric acid",

author = "Mengqing Xia and Junjie Wang and Jianhua Sheng and Yingying Tang and Chunyan Li and Kelvin Lim and Bin He and Chunbo Li and Yifeng Xu and Jijun Wang",

note = "Funding Information: From the *Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; Departments of †Psychiatry and ‡Biomedical Engineering, University of Minnesota, Minneapolis, MN; §CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Science; ||Brain Science and Technology Research Center, and ¶Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China. Received for publication July 21, 2017; accepted March 29, 2018. Reprints: Jijun Wang, PhD, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Rd, Shanghai 200030, China (e‐mail: jijunwang27@163.com); or Yingying Tang, PhD, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Rd, Shanghai 200030, China (e‐mail: yytang0522@gmail.com). This work was supported by grants from Ministry of Science and Technology of the People{\textquoteright}s Republic of China (2016YFC1306803), National Natural Science Foundation of China (81671329 and 81671332), Program of Shanghai Academic/Technology Research Leader (16XD1402400), Shanghai Science and Technology Committee (16JC1420200 and 17ZR1424700), National Key Clinical Disciplines at Shanghai Mental Health Center (OMA-MH, 2011-873), Shanghai Key Laboratory of Psychotic Disorders (13dz2260500), Shanghai Jiao Tong University Foundation (14JCRY04 and YG2014MS40), SHSMU-ION Research Center for Brain Disorders (2015NKX001, 15ZH2015, and W35XT), Medicine Engineering Intersection Program of Shanghai Jiaotong University (YG2015ZD12), and Shanghai Hospital Development Center (16CR2015A and 16CR3017A). The authors have no conflicts of interest or financial disclosures to report. M.X. and J.W. equally contributed to this work. Copyright {\textcopyright} 2018 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000507 Conclusions: γ-Aminobutyric acid level in the medial prefrontal lobe was reduced in schizophrenia patients. An increase in GABA concentration in the medial prefrontal cortex is more significantly associated with ECT plus antipsychotics than antipsychotics alone, possibly supporting the hypothesis of ECT augmentation for GABA mediated neural inhibition. Publisher Copyright: {\textcopyright} Wolters Kluwer Health, Inc. All rights reserved 2017.",

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TY - JOUR

T1 - Effect of Electroconvulsive Therapy on Medial Prefrontal γ-Aminobutyric Acid among Schizophrenia Patients

T2 - A Proton Magnetic Resonance Spectroscopy Study

AU - Xia, Mengqing

AU - Wang, Junjie

AU - Sheng, Jianhua

AU - Tang, Yingying

AU - Li, Chunyan

AU - Lim, Kelvin

AU - He, Bin

AU - Li, Chunbo

AU - Xu, Yifeng

AU - Wang, Jijun

N1 - Funding Information: From the *Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; Departments of †Psychiatry and ‡Biomedical Engineering, University of Minnesota, Minneapolis, MN; §CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Science; ||Brain Science and Technology Research Center, and ¶Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China. Received for publication July 21, 2017; accepted March 29, 2018. Reprints: Jijun Wang, PhD, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Rd, Shanghai 200030, China (e‐mail: jijunwang27@163.com); or Yingying Tang, PhD, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Rd, Shanghai 200030, China (e‐mail: yytang0522@gmail.com). This work was supported by grants from Ministry of Science and Technology of the People’s Republic of China (2016YFC1306803), National Natural Science Foundation of China (81671329 and 81671332), Program of Shanghai Academic/Technology Research Leader (16XD1402400), Shanghai Science and Technology Committee (16JC1420200 and 17ZR1424700), National Key Clinical Disciplines at Shanghai Mental Health Center (OMA-MH, 2011-873), Shanghai Key Laboratory of Psychotic Disorders (13dz2260500), Shanghai Jiao Tong University Foundation (14JCRY04 and YG2014MS40), SHSMU-ION Research Center for Brain Disorders (2015NKX001, 15ZH2015, and W35XT), Medicine Engineering Intersection Program of Shanghai Jiaotong University (YG2015ZD12), and Shanghai Hospital Development Center (16CR2015A and 16CR3017A). The authors have no conflicts of interest or financial disclosures to report. M.X. and J.W. equally contributed to this work. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000507 Conclusions: γ-Aminobutyric acid level in the medial prefrontal lobe was reduced in schizophrenia patients. An increase in GABA concentration in the medial prefrontal cortex is more significantly associated with ECT plus antipsychotics than antipsychotics alone, possibly supporting the hypothesis of ECT augmentation for GABA mediated neural inhibition. Publisher Copyright: © Wolters Kluwer Health, Inc. All rights reserved 2017.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Objective Electroconvulsive therapy ECT has often been applied to augment antipsychotics for schizophrenia patients. However, the underpinning mechanism is still unclear. Previous studies of major depressive disorder reported an increase in γ-aminobutyric acid GABA after ECT. The present study investigated the effects of ECT on medial prefrontal GABA in schizophrenia using a proton magnetic resonance spectroscopy. Methods Inpatients fulfilling the diagnostic criteria for schizophrenia Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were assigned to 2 groups, ECT group n = 14 receiving ECT plus antipsychotic drugs APD and drug group n = 17 only receiving antipsychotic drugs. Medial prefrontal GABA+/Cr concentrations of all patients were measured with magnetic resonance spectroscopy at baseline and after 4-week treatment. Sex- and age-matched healthy comparisons n = 19 were scanned at baseline. Results γ-Aminobutyric acid level did not show a significant difference among 3 groups. However, when 2 patient groups were combined, their GABA level was significantly lower than that in healthy comparisons group. For schizophrenia patients, repeated measures analysis of variance revealed that both the group effect and group × time interaction were insignificant, but the time effect of baseline versus after treatment was significant. Exploratory post hoc paired t test found a significant increase of GABA only in ECT group, but not in drug group. No correlation was found between GABA change and clinical symptom improvement in either group. Conclusions γ-Aminobutyric acid level in the medial prefrontal lobe was reduced in schizophrenia patients. An increase in GABA concentration in the medial prefrontal cortex is more significantly associated with ECT plus antipsychotics than antipsychotics alone, possibly supporting the hypothesis of ECT augmentation for GABA mediated neural inhibition.

AB - Objective Electroconvulsive therapy ECT has often been applied to augment antipsychotics for schizophrenia patients. However, the underpinning mechanism is still unclear. Previous studies of major depressive disorder reported an increase in γ-aminobutyric acid GABA after ECT. The present study investigated the effects of ECT on medial prefrontal GABA in schizophrenia using a proton magnetic resonance spectroscopy. Methods Inpatients fulfilling the diagnostic criteria for schizophrenia Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were assigned to 2 groups, ECT group n = 14 receiving ECT plus antipsychotic drugs APD and drug group n = 17 only receiving antipsychotic drugs. Medial prefrontal GABA+/Cr concentrations of all patients were measured with magnetic resonance spectroscopy at baseline and after 4-week treatment. Sex- and age-matched healthy comparisons n = 19 were scanned at baseline. Results γ-Aminobutyric acid level did not show a significant difference among 3 groups. However, when 2 patient groups were combined, their GABA level was significantly lower than that in healthy comparisons group. For schizophrenia patients, repeated measures analysis of variance revealed that both the group effect and group × time interaction were insignificant, but the time effect of baseline versus after treatment was significant. Exploratory post hoc paired t test found a significant increase of GABA only in ECT group, but not in drug group. No correlation was found between GABA change and clinical symptom improvement in either group. Conclusions γ-Aminobutyric acid level in the medial prefrontal lobe was reduced in schizophrenia patients. An increase in GABA concentration in the medial prefrontal cortex is more significantly associated with ECT plus antipsychotics than antipsychotics alone, possibly supporting the hypothesis of ECT augmentation for GABA mediated neural inhibition.

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KW - proton magnetic resonance spectroscopy

KW - schizophrenia

KW - γ-aminobutyric acid

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Effect of Electroconvulsive Therapy on Medial Prefrontal γ-Aminobutyric Acid among Schizophrenia Patients: A Proton Magnetic Resonance Spectroscopy Study

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