Guusjie Collin1,2,3, Larry J. Seidman1,4, Matcheri S. Keshevan1, Zhenghan Qi5, William S. Stone1, Tianhong Zhang6, Margaret A Niznikiewicz7, Martha E Shenton3,7, Jijun Wang6, Susan Whitfield-Gabrieli2; 1Beth Israel Deaconess Medical Center, Harvard Medical School, 2McGovern Institute for Brain Research, Massachusetts Institute of Technology, 3Brigham and Women’s Hospital, Harvard Medical School, 4Massachusetts General Hospital, Harvard Medical School, 5University of Delaware, 6Shanghai Mental Health Center, Shanghai Jaio Tong University School of Medicine, 7Veterans Affairs Boston Healthcare System
Purpose: Prodromal symptoms progressing into psychosis may involve a functional reorganization of the connectome. In this study, we performed a functional connectome analysis in a large group of adolescents and young adults at Clinical High Risk (CHR) for psychosis. We aimed to assess whether, and if so how, baseline connectome organization distinguishes CHRs that go on to develop psychosis. Materials and methods: A total of 251 subjects, including 158 CHRs and 93 matched healthy controls (HCs), participated in this study. Prodromal symptoms and cognition were assessed using validated procedures. MRI scans were processed with Freesurfer v6.0 and CONN v17.d software to produce functional connectome maps that were analyzed using Louvain community detection. For each CHR, we assessed how similar their modular organization was relative to a group-averaged HC network using the rand similarity coefficient. Results: Modular connectome organization of CHRs who developed psychosis was significantly less similar to HCs than CHRs who did not convert (F(1,154) = 7.14, p = 0.008). Superior and medial temporal and ventromedial prefrontal regions were most abnormal in terms of modular assignment. Furthermore, Kaplan-Meier analysis showed reduced psychosis-free survival in CHRs with abnormal baseline connectome organization, with an approximately 3-fold risk of conversion to psychosis. Cox regression analysis indicated that modular connectome organization, gender, and IQ predicted time to conversion. Conclusion: Abnormal functional connectome organization precedes the onset of psychosis and is associated with increased conversion rates in CHRs. Our results suggest that a reorganization of the functional connectome may accompany the manifestation of psychosis.
