Extra-axial Cerebrospinal Fluid Relationships to Infant Brain Structure, Cognitive Development, and Risk for Schizophrenia

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 (TD) children or in children at risk for schizophrenia (SCZHR). METHODS:3T magnetic resonance imaging scans were obtained in TD children (n = 105) and in SCZHR children (n = 38) at 1 and 2 years of age. EA-CSF volume and several measures of brain structure were generated, including global tissue volumes, cortical thickness, and surface area. Cognitive and motor abilities at 1 and 2 years of age 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 1 and 2 years of age. In contrast, EA-CSF volume was negatively associated with average cortical thickness. Lower motor ability was associated with increased EA-CSF volume at 1 year of age. EA-CSF was not significantly increased in SCZHR children compared with TD children. CONCLUSIONS:EA-CSF volume is positively associated with overall brain size and cortical surface area but negatively associated with cortical thickness. 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 in the SCZHR group 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.