Characteristics of cerebrospinal fluid in autism spectrum disorder - A systematic review

Autism Spectrum Disorder (ASD) is a range of neurodevelopmental conditions characterized by impaired social interaction, learning, and restricted or repetitive behaviors. The underlying causes of ASD are still debated, but researchers have found many physiological traits like gut problems and impaired immune system to help understand the etiology of ASD. Cerebrospinal fluid (CSF) plays a critical role in maintaining the homeostasis of the neuronal environment and has, therefore, been analyzed in multiple conditions impacting the central nervous system. The study of CSF is crucial to understanding neurological disorders as its composition changes with the disorders, and these changes may indicate various disorder-related physiological mechanisms. For this systematic review, we searched PubMed, Scopus, and Web of Science for studies published between 1977 and 2025 and selected 49 studies after manual screening. We took stock of the evidence supporting the hypothesis that ASD alters the properties and composition of CSF. We systematically report on the different attributes of CSF in the ASD population that could be potential biomarkers and assist in understanding the origins and progression of ASD. We found that in CSF, immune markers, proteins, extra-axial CSF, folate, oxytocin, and vasopressin showed changes in ASD compared to the neurotypicals. We observed gaps in the literature due to variations in age and sample size and noted biases related to sex (i.e., samples are predominantly including male participants) and age (i.e., a handful of studies were conducted on adults). Our review highlights the need for more research on CSF in ASD to improve our understanding of this disorder and identify CSF biomarkers.