title: Cerebello-thalamo-cortical networks predict positive symptom progression in individuals at ultra-high risk for psychosis.
abstract: Prospective longitudinal evaluation of adolescents at ultra-high-risk (UHR) for the development of psychosis enables an enriched neurodevelopmental perspective of disease progression in the absence of many of the factors that typically confound research with formally psychotic patients (antipsychotic medications, drug/alcohol dependence). The cerebellum has been linked to cognitive dysfunction and symptom severity in schizophrenia and recent work from our team suggests that it is a promising target for investigation in UHR individuals as well. However, the cerebellum and cerebello-thalamo-cortical networks have not been investigated developmentally or with respect to disease progression in this critical population. Further, to date, the types of longitudinal multimodal connectivity studies that would substantially inform our understanding of this area have not yet been conducted. In the present investigation 26 UHR and 24 healthy control adolescents were administered structured clinical interviews and scanned at baseline and then again at 12-month time points to investigate both functional and structural connectivity development of cerebello-thalamo-cortical networks in conjunction with symptom progression. Our results provide evidence of abnormal functional and structural cerebellar network development in the UHR group. Crucially, we also found that cerebello-thalamo-cortical network development and connectivity at baseline are associated with positive symptom course, suggesting that cerebellar networks may be a biomarker of disease progression. Together, these findings provide support for neurodevelopmental models of psychotic disorders and suggest that the cerebellum and respective networks with the cortex may be especially important for elucidating the pathophysiology of psychosis and highlighting novel treatment targets.
authors.affiliation: Department of Psychology, Texas A&M University, United States; Texas A&M Institute for Neuroscience, Texas A&M University, United States; Department of Psychology & Neuroscience, University of Colorado Boulder, United States.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Bernard
authors.affiliation: Department of Psychology, Texas A&M University, United States; Texas A&M Institute for Neuroscience, Texas A&M University, United States; Institute of Cognitive Science, University of Colorado Boulder, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Orr
authors.affiliation: Department of Psychology & Neuroscience, University of Colorado Boulder, United States; Center for Neuroscience, University of Colorado Boulder, United States; Department of Psychology, Northwestern University, United States.
authors.forename: Vijay A
authors.initials: VA
authors.lastname: Mittal
mesh_terms: D000293:Adolescent; D002531:Cerebellum / Q000000981:diagnostic imaging*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging*; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology; D012146:Rest; D013788:Thalamus / Q000000981:diagnostic imaging*; D066127:White Matter / Q000000981:diagnostic imaging / Q000254:growth & development; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Cerebellum; Diffusion tensor imaging; Functional connectivity; Longitudinal; Neuroimaging; Psychosis risk