Cerebrospinal Fluid Vasopressin Concentration Is a Biomarker of Autistic Social Impairment and Hypothalamic Vasopressin Gene Expression in Humans

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social interaction difficulties and restricted, repetitive behaviors. Recent ASD biomarker discovery efforts have found that cerebrospinal fluid (CSF) concentration of vasopressin, a hypothalamic neuropeptide critical for mammalian social functioning, is significantly lower in children with ASD and newborns later diagnosed with ASD. Low CSF vasopressin concentration is also linked to ASD social (but not repetitive) behavior symptom severity. These findings suggest that CSF vasopressin measurement may have clinical utility, but CSF surveillance requires invasive sampling procedures that will be difficult to integrate into routine clinical care without strong justification (i.e., CSF vasopressin is a valid proxy for hypothalamic vasopressin production, whereas blood vasopressin is not). We therefore obtained neuropathological specimens and patient data (N = 18) to investigate this possibility. In Study 1, we capitalized on the unique opportunity to test the reproducibility and robustness of the relationship between CSF vasopressin concentration and ASD behavioral symptoms in a sample demographically and methodologically distinct from prior work. This relationship held across age, antemortem to postmortem biospecimens, quantification platforms, clinical instruments, evaluators, and symptom type. In Study 2, we found in concomitantly collected postmortem samples that CSF vasopressin concentration significantly and positively predicted hypothalamic vasopressin gene expression, whereas blood vasopressin concentration did not. These findings establish CSF vasopressin as a brain-derived, mechanistically relevant biomarker of social difficulties in ASD, and suggest that CSF vasopressin measurement may be useful for ASD detection and/or identification of individuals who will benefit from pharmacological enhancement of brain vasopressin signaling.