TY - JOUR
T1 - Cerebellar Gray Matter Volume Is Associated With Cognitive Function and Psychopathology in Adolescence
AU - Moberget, Torgeir
AU - Alnaes, Dag
AU - Kaufmann, Tobias
AU - Nhat Trung Doan, null
AU - COrdova-Palomera, Aldo
AU - Norbom, Linn Bonaventure
AU - Rokicki, Jaroslav
AU - van der Meer, Dennis
AU - Andreassen, Ole A.
AU - Westlye, Lars T.
N1 - Funding Information:
This work was supported by the European Commission Seventh Framework Programme (Grant No. 602450 to IMAGEMEND), Research Council of Norway (Grant Nos. 213837 , 223273 , 229129 , 204966/F20 , 249795 , and 251134 ), South-Eastern Norway Regional Health Authority (Grant Nos. 2013-123 , 2014-097 , 2015-073 , 2016-083 , and 2017112 ), and K.G. Jebsen Foundation . The Philadelphia Neurodevelopment Cohort sample is a publicly available data set. Support for the collection of the data sets was provided by the National Institute of Mental Health (Grant No. RC2MH089983 to Raquel Gur, M.D., Ph.D., and Grant No. RC2MH089924 to Hakon Hakonarson, M.D., Ph.D.). All participants were recruited through the Center for Applied Genomics at Children’s Hospital of Philadelphia.
Publisher Copyright:
© 2019 Society of Biological Psychiatry
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
KW - Adolescence
KW - Cerebellum
KW - Conduct disorder
KW - Psychopathology
KW - Psychosis
KW - Voxel-based morphometry
KW - PHILADELPHIA NEURODEVELOPMENTAL COHORT
KW - ENVIRONMENTAL RISK-FACTORS
KW - SUBSTANCE USE DISORDERS
KW - AGE-OF-ONSET
KW - MENTAL-DISORDERS
KW - PSYCHIATRIC-DISORDERS
KW - LIFETIME PREVALENCE
KW - PRODROMAL SYMPTOMS
KW - BRAIN-DEVELOPMENT
KW - EXECUTIVE SYSTEM
U2 - 10.1016/j.biopsych.2019.01.019
DO - 10.1016/j.biopsych.2019.01.019
M3 - Article
SN - 0006-3223
VL - 86
SP - 65
EP - 75
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 1
ER -