The cerebrospinal fluid system in children with autism spectrum disorder

ABSTRACT The cerebrospinal fluid (CSF) system is an understudied area of research in the context of autism spectrum disorder (ASD) despite its known role in development. For example, the delivery of growth factors through CSF circulation and the CSF pressure generated by normal CSF production are both essential for embryonic brain development. Recent lines of evidence demonstrate that components involved in the CSF system, namely the perivascular spaces (PVS) and choroid plexus, are altered in individuals with ASD. The PVS is the site where metabolic waste is cleared from the brain by means of the CSF while the choroid plexus produces CSF and regulates the composition of CSF. Enlarged PVS is a marker of altered glymphatic CSF clearance and has been observed in individuals with ASD. A diffusion magnetic resonance imaging (MRI) metric that measures diffusion along the PVS (DTI-ALPS) and is often found to be lower in conditions with impaired glymphatic function is lower in children with ASD. In terms of the choroid plexus, initial reports show enlarged volume and altered texture in the choroid plexus in individuals with ASD. Preliminary data from our group shows that the choroid plexus volume is significantly larger in adults with ASD compared to matched controls. Additionally, larger choroid plexus was associated with more severe ASD symptoms. Despite being closely related, no study has investigated the relationship between PVS measures (PVS volume, DTI-ALPS index) and choroid plexus volume in individuals with ASD to date. Intriguingly, our preliminary data show that lower DTI-ALPS index (i.e., found in conditions with impaired glymphatic function) is associated with larger choroid plexus volume in male adults with ASD. This project will leverage data from a publicly available dataset, the Autism Brain Imaging Data Exchange II, to assess PVS measures (PVS volume, DTI-ALPS index) and choroid plexus volume in boys with ASD and controls, aged 5-12. By focusing on a cohort of children, we can learn if alterations are present at an early stage. We will be able to evaluate 1) whether PVS measures or choroid plexus volume are altered in boys with ASD compared to matched controls, 2) whether there are any associations between PVS measures and choroid plexus volume in ASD and controls, and 3) whether PVS measures and choroid plexus volume are associated with ASD symptom severity.