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Published Online: 24 June 2019

Altered Cellular White Matter But Not Extracellular Free Water on Diffusion MRI in Individuals at Clinical High Risk for Psychosis

Yingying Tang, Ph.D., Ofer Pasternak, Ph.D. [email protected], Marek Kubicki, M.D., Ph.D., Yogesh Rathi, Ph.D., Tianhong Zhang, M.D., Ph.D., Junjie Wang, Ph.D., Huijun Li, Ph.D., Kristen A. Woodberry, M.S.W., Ph.D., Lihua Xu, Ph.D., Zhenying Qian, B.A., Anni Zhu, B.A., Susan Whitfield-Gabrieli, Ph.D., Matcheri S. Keshavan, M.D., Margaret Niznikiewicz, Ph.D., William S. Stone, Ph.D., Robert W. McCarley, M.D., Martha E. Shenton, Ph.D., Jijun Wang, M.D., Ph.D. [email protected], and Larry J. Seidman, Ph.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 176, Number 10
https://doi.org/10.1176/appi.ajp.2019.18091044
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Abstract

Objective:

Detecting brain abnormalities in clinical high-risk populations before the onset of psychosis is important for tracking pathological pathways and for identifying possible intervention strategies that may impede or prevent the onset of psychotic disorders. Co-occurring cellular and extracellular white matter alterations have previously been implicated after a first psychotic episode. The authors investigated whether or not cellular and extracellular alterations are already present in a predominantly medication-naive cohort of clinical high-risk individuals experiencing attenuated psychotic symptoms.

Methods:

Fifty individuals at clinical high risk, of whom 40 were never medicated, were compared with 50 healthy control subjects, group-matched for age, gender, and parental socioeconomic status. 3-T multishell diffusion MRI data were obtained to estimate free-water imaging white matter measures, including fractional anisotropy of cellular tissue (FAT) and the volume fraction of extracellular free water (FW).

Results:

Significantly lower FAT was observed in the clinical high-risk group compared with the healthy control group, but no statistically significant FW alterations were observed between groups. Lower FAT in the clinical high-risk group was significantly associated with a decline in Global Assessment of Functioning Scale (GAF) score compared with highest GAF score in the previous 12 months.

Conclusions:

Cellular but not extracellular alterations characterized the clinical high-risk group, especially in those who experienced a decline in functioning. These cellular changes suggest an early deficit that possibly reflects a predisposition to develop attenuated psychotic symptoms. In contrast, extracellular alterations were not observed in this clinical high-risk sample, suggesting that previously reported extracellular abnormalities may reflect an acute response to psychosis, which plays a more prominent role closer to or at onset of psychosis.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 176 • Number 10 • October 01, 2019
Pages: 820 - 828
PubMed: 31230461

History

Received: 9 September 2018
Revision received: 9 January 2019
Revision received: 5 March 2019
Accepted: 1 April 2019
Published online: 24 June 2019
Published in print: October 01, 2019

Keywords

  1. Psychosis
  2. Clinical High-Risk
  3. Diffusion Tensor Imaging
  4. Free Water
  5. White Matter
  6. Neurodevelopment

Authors

Affiliations

Yingying Tang, Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Ofer Pasternak, Ph.D. [email protected]
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Marek Kubicki, M.D., Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Yogesh Rathi, Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Tianhong Zhang, M.D., Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Junjie Wang, Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Huijun Li, Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Kristen A. Woodberry, M.S.W., Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Lihua Xu, Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Zhenying Qian, B.A.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Anni Zhu, B.A.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Susan Whitfield-Gabrieli, Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Matcheri S. Keshavan, M.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Margaret Niznikiewicz, Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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William S. Stone, Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Robert W. McCarley, M.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Martha E. Shenton, Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Jijun Wang, M.D., Ph.D. [email protected]
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Larry J. Seidman, Ph.D.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Tang, Zhang, Junjie Wang, Xu, Qian, Jijun Wang); the Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston (Tang, Pasternak, Kubicki, Rathi, Zhang, Zhu, Shenton); the Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston (Pasternak, Kubicki, Rathi, Shenton); the Institute of Mental Health, Suzhou Psychiatric Hospital, Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China (Junjie Wang); the Department of Psychology, Florida A&M University, Tallahassee (Li); the Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (Woodberry, Keshavan, Stone, Seidman); the McGovern Institute for Brain Research and the Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge (Whitfield-Gabrieli); the Department of Psychiatry (Niznikiewicz, McCarley) and Research and Development (Shenton), Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, Mass.; the Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China (Jijun Wang); the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, China (Jijun Wang); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Seidman).
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Notes

Send correspondence to Dr. Jijun Wang ([email protected]) and Dr. Pasternak ([email protected]).

Author Contributions

Drs. Tang and Pasternak contributed equally and share first authorship. Drs. Shenton, Jijun Wang, and Seidman contributed equally and share senior authorship.

Competing Interests

The authors report no financial relationships with commercial interests.

Funding Information

Science and Technology Commission of Shanghai Municipalityhttp://dx.doi.org/10.13039/501100003399: 16JC1420200, 17411953100
Shanghai Municipal Human Resources and Social Security Bureauhttp://dx.doi.org/10.13039/501100009018: 2017YQ069
National Institute of Mental Healthhttp://dx.doi.org/10.13039/100000025: K23MH102358, R01MH074794, R01MH101052, R01MH102377, R01MH108574, R01MH111448
National Nature Science Foundation of China: 81361120403, 81671329, 81671332
Ministry of Science and Technology of China, National Key R&D Program of China: 2016YFC1306800
U.S. Department of Veterans Affairshttp://dx.doi.org/10.13039/100000738: CX000157, CX000176
Supported by Ministry of Science and Technology of China, National Key R&D Program of China grant 2016YFC1306800; NIMH grants R01MH101052, R01MH111448, R01MH074794, R01MH102377, R01MH108574, and K23MH102358; National Nature Science Foundation of China grants 81361120403, 81671332, 81671329, and 81871050; VA grants 2I01 CX000176 and CX000157; Shanghai Science and Technology Committee grants 16JC1420200 and 17411953100; and Clinical Research Center at Shanghai Mental Health Center grants CRC2018ZD01, CRC2018ZD04, and CRC2018YB01. Dr. Tang was funded by a Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2017YQ069).

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