Extra-axial CSF relationships to infant brain structure, cognitive development, and risk for schizophrenia

Abstract Background Increased volume of extra-axial cerebrospinal fluid (EA-CSF) is associated with autism spectrum disorder diagnosis in young children. However, little is known about EA-CSF development in typically developing children or in children at risk for schizophrenia. Methods 3T magnetic resonance imaging scans were obtained in typically developing children (TD; N=105) and in children at risk for schizophrenia (SCZHR; N=38) at ages 1 and 2 years. EA-CSF volume and several measures of brain structure were generated, including global tissue volumes, cortical thickness (CT), and surface area (SA). Cognitive and motor abilities at 1 and 2 years were assessed using the Mullen Scales of Early Learning. Results In the TD children, EA-CSF volume was positively associated with total brain volume, gray and white matter volumes, and total surface area at ages 1 and 2 years. In contrast, EA-CSF volume was negatively associated with average CT. Lower motor ability was associated with increased EA-CSF volume at age 1. EA-CSF was not significantly increased in SCZHR children compared to TD children. Conclusions EA-CSF volume is positively associated with overall brain size and cortical surface area, but negatively associated with CT. Increased EA-CSF is associated with delayed motor development at 1 year of age, similar to studies of children at risk for autism, suggesting that increased EA-CSF may be an early biomarker of abnormal brain development in infancy. Infants at risk for schizophrenia did not exhibit significantly increased EA-CSF, suggesting that increased EA-CSF could be specific to neurodevelopmental disorders with an earlier onset, such as autism.