Abnormal Function in Dentate Nuclei Precedes the Onset of Psychosis: A Resting-State fMRI Study in High-Risk Individuals

• Published in: Schizophrenia bulletin Vol. 47; no. 5; pp. 1421 - 1430
• Main Authors: Anteraper, Sheeba Arnold, Guell, Xavier, Collin, Guusje, Qi, Zhenghan, Ren, Jingwen, Nair, Atira, Seidman, Larry J, Keshavan, Matcheri S, Zhang, Tianhong, Tang, Yingying, Li, Huijun, McCarley, Robert W, Niznikiewicz, Margaret A, Shenton, Martha E, Stone, William S, Wang, Jijun, Whitfield-Gabrieli, Susan
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.09.2021
• Subjects: Adolescent; Adult; Cerebellar Nuclei - diagnostic imaging; Cerebellar Nuclei - physiopathology; Connectome; Default Mode Network - diagnostic imaging; Default Mode Network - physiopathology; Disease Progression; Disease Susceptibility; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Nerve Net - diagnostic imaging; Nerve Net - physiopathology; Psychosis; Psychotic Disorders - diagnostic imaging; Psychotic Disorders - physiopathology; Regular; Risk; Schizophrenia; Schizophrenia - diagnostic imaging; Schizophrenia - physiopathology; Young Adult; resting-state functional connectivity; schizophrenia; cerebellum; psychosis
• ISSN: 0586-7614; 1745-1701; 1745-1701
• DOI: 10.1093/schbul/sbab038

Abstract Objective The cerebellum serves a wide range of functions and is suggested to be composed of discrete regions dedicated to unique functions. We recently developed a new parcellation of the dentate nuclei (DN), the major output nuclei of the cerebellum, which optimally divides the structure into 3 functional territories that contribute uniquely to default-mode, motor-salience, and visual processing networks as indexed by resting-state functional connectivity (RsFc). Here we test for the first time whether RsFc differences in the DN, precede the onset of psychosis in individuals at risk of developing schizophrenia. Methods We used the magnetic resonance imaging (MRI) dataset from the Shanghai At Risk for Psychosis study that included subjects at high risk to develop schizophrenia (N = 144), with longitudinal follow-up to determine which subjects developed a psychotic episode within 1 year of their functional magnetic resonance imaging (fMRI) scan (converters N = 23). Analysis used the 3 functional parcels (default-mode, salience-motor, and visual territory) from the DN as seed regions of interest for whole-brain RsFc analysis. Results RsFc analysis revealed abnormalities at baseline in high-risk individuals who developed psychosis, compared to high-risk individuals who did not develop psychosis. The nature of the observed abnormalities was found to be anatomically specific such that abnormal RsFc was localized predominantly in cerebral cortical networks that matched the 3 functional territories of the DN that were evaluated. Conclusions We show for the first time that abnormal RsFc of the DN may precede the onset of psychosis. This new evidence highlights the role of the cerebellum as a potential target for psychosis prediction and prevention.