The emergence of prodromal symptoms of schizophrenia and their evolution into overt psychosis may stem from an aberrant functional reorganization of the brain during adolescence. To examine whether abnormalities in connectome organization precede psychosis onset, we performed a functional connectome analysis in a large cohort of medication-naive youth at risk for psychosis from the Shanghai At Risk for Psychosis (SHARP) study. The SHARP program is a longitudinal study of adolescents and young adults at Clinical High Risk (CHR) for psychosis, conducted at the Shanghai Mental Health Center in collaboration with neuroimaging laboratories at Harvard and MIT. Our study involved a total of 251 subjects, including 158 CHRs and 93 age-, sex-, and education-matched healthy controls. During 1-year follow-up, 23 CHRs developed psychosis. CHRs who would go on to develop psychosis were found to show abnormal modular connectome organization at baseline, while CHR non-converters did not. In all CHRs, abnormal modular connectome organization at baseline was associated with a threefold conversion rate. A region-specific analysis showed that brain regions implicated in early-course schizophrenia, including superior temporal gyrus and anterior cingulate cortex, were most abnormal in terms of modular assignment. Our results show that functional changes in brain network organization precede the onset of psychosis and may drive psychosis development in at-risk youth.

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Deceased authors: Larry J. Seidman, Robert W. McCarley


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This study was supported by the Ministry of Science and Technology of China (2016 YFC 1306803) and US National Institute of Mental Health (R21 MH 093294, R01 MH 101052, and R01 MH 111448). GC was supported by an EU Marie Curie Global Fellowship (Grant no. 749201); MSK was supported by an NIMH Grant (R01 MH 64023); MES and RWM were supported by a VA Merit Award.

Author contributions

LJS passed away on 7 September 2017 and RWM passed away on 27 May 2017. LJS and RWM were two of the initiators and principal investigators of the Shanghai At Risk for Psychosis (SHARP) study.

Author information


  1. Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    • Guusje Collin
    • , Larry J. Seidman
    • , Matcheri S. Keshavan
    • , William S. Stone
    •  & Zhenghan Qi
  2. McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA

    • Guusje Collin
    • , Sheeba Arnold Anteraper
    •  & Susan Whitfield-Gabrieli
  3. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    • Guusje Collin
    •  & Martha E. Shenton
  4. Department of Linguistics and Cognitive Science, University of Delaware, Newark, DE, USA

    • Zhenghan Qi
  5. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    • Tianhong Zhang
    • , Yingying Tang
    •  & Jijun Wang
  6. Department of Psychology, Florida A&M University, Tallahassee, FL, USA

    • Huijun Li
  7. Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder, Massachusetts General Hospital, Boston, MA, USA

    • Sheeba Arnold Anteraper
  8. Department of Psychiatry, VA Boston Healthcare System, Brockton Division, Brockton, MA, USA

    • Margaret A. Niznikiewicz
    •  & Robert W. McCarley
  9. Research and Development, VA Boston Healthcare System, Brockton Division, Brockton, MA, USA

    • Martha E. Shenton
  10. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    • Martha E. Shenton
  11. Poitras Center for Affective Disorders, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA

    • Susan Whitfield-Gabrieli


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The authors declare that they have no conflict of interest.

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Correspondence to Guusje Collin or Jijun Wang.

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