Torgeir Moberget1, Dag Alnæs2, Tobias Kaufmann2, Nhat Trung Doan2, Aldo Córdova-Palomera2, Linn Bonaventure Norbom3, Jaroslav Rokicki3, Dennis van der Meer2, Ole A Andreassen2, Lars T Westlye3. 1. Norwegian Centre for Mental Disorders Research, K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: torgeir.moberget@gmail.com. 2. Norwegian Centre for Mental Disorders Research, K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 3. Norwegian Centre for Mental Disorders Research, K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
Abstract
BACKGROUND: Accumulating evidence supports cerebellar involvement in mental disorders, such as schizophrenia, bipolar disorder, depression, anxiety disorders, and attention-deficit/hyperactivity disorder. However, little is known about the cerebellum in developmental stages of these disorders. In particular, whether cerebellar morphology is associated with early expression of specific symptom domains remains unclear. METHODS: We used machine learning to test whether cerebellar morphometric features could robustly predict general cognitive function and psychiatric symptoms in a large and well-characterized developmental community sample centered on adolescence (Philadelphia Neurodevelopmental Cohort, n = 1401, age 8-23 years). RESULTS: Cerebellar morphology was associated with both general cognitive function and general psychopathology (mean correlations between predicted and observed values: r = .20 and r = .13; p < .001). Analyses of specific symptom domains revealed significant associations with rates of norm-violating behavior (r = .17; p < .001) as well as psychosis (r = .12; p < .001) and anxiety (r = .09; p = .012) symptoms. In contrast, we observed no associations with attention deficits or depressive, manic, or obsessive-compulsive symptoms. Crucially, across 52 brain-wide anatomical features, cerebellar features emerged as the most important for prediction of general psychopathology, psychotic symptoms, and norm-violating behavior. Moreover, the association between cerebellar volume and psychotic symptoms and, to a lesser extent, norm-violating behavior remained significant when adjusting for several potentially confounding factors. CONCLUSIONS: The robust associations with psychiatric symptoms in the age range when these typically emerge highlight the cerebellum as a key brain structure in the development of severe mental disorders.
BACKGROUND: Accumulating evidence supports cerebellar involvement in mental disorders, such as schizophrenia, bipolar disorder, depression, anxiety disorders, and attention-deficit/hyperactivity disorder. However, little is known about the cerebellum in developmental stages of these disorders. In particular, whether cerebellar morphology is associated with early expression of specific symptom domains remains unclear. METHODS: We used machine learning to test whether cerebellar morphometric features could robustly predict general cognitive function and psychiatric symptoms in a large and well-characterized developmental community sample centered on adolescence (Philadelphia Neurodevelopmental Cohort, n = 1401, age 8-23 years). RESULTS: Cerebellar morphology was associated with both general cognitive function and general psychopathology (mean correlations between predicted and observed values: r = .20 and r = .13; p < .001). Analyses of specific symptom domains revealed significant associations with rates of norm-violating behavior (r = .17; p < .001) as well as psychosis (r = .12; p < .001) and anxiety (r = .09; p = .012) symptoms. In contrast, we observed no associations with attention deficits or depressive, manic, or obsessive-compulsive symptoms. Crucially, across 52 brain-wide anatomical features, cerebellar features emerged as the most important for prediction of general psychopathology, psychotic symptoms, and norm-violating behavior. Moreover, the association between cerebellar volume and psychotic symptoms and, to a lesser extent, norm-violating behavior remained significant when adjusting for several potentially confounding factors. CONCLUSIONS: The robust associations with psychiatric symptoms in the age range when these typically emerge highlight the cerebellum as a key brain structure in the development of severe mental disorders.
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