Interdisciplinary Initiatives Program Round 6 - 2012

Karen Parker, Psychiatry
Antonio Hardan, Psychiatry
Joshua Elias, Chemical and Systems Biology
Sonia Partap, Neurology

Autism spectrum disorders (ASD), which are characterized by social impairments, remain poorly understood. Early and accurate diagnoses are difficult and no effective medical treatments exist. ASD are diagnosed on the basis of behavioral criteria and no biomarkers have been identified. Biomarkers are molecules that indicate a disease state. They increase our ability to make accurate diagnoses and provide a biological target for drug development.

One promising biomarker is the neuropeptide oxytocin, which is critical for social functioning. Animal studies have shown that impairments in brain oxytocin produce diverse social deficits. While oxytocin is found in the blood, relationships between blood and brain sources of oxytocin are poorly understood. Although there is some evidence indicating that blood levels of oxytocin are abnormal in autism, animal studies suggest that oxytocin levels in cerebrospinal fluid (CSF) may more directly predict social functioning. Despite the obvious need, no studies to date have examined CSF oxytocin levels, or relationships between CSF oxytocin levels and social functioning, in people with autism.

Examining biomarkers of social functioning requires invasive CSF sampling, gold-standard social assessments, and careful biomarker quantification. Our cross-disciplinary research team comprised of both clinicians and basic scientists possesses the unique combination of skills and access to patient cohorts required to accomplish these tasks. We therefore are uniquely poised to capitalize on the extremely rare and unprecedented opportunity to collect CSF and blood samples from children with and without autism who are being evaluated in Stanford University medical clinics. These participants will subsequently undergo extensive social assessments. Their biological samples will then be evaluated for impaired oxytocin signaling and screened for other molecules in the CSF that may provide insight into autism’s underlying biology.

Our project has the following three aims: (1) Test whether children with autism have lower oxytocin levels (in CSF and blood) compared to children without autism, and determine the relationship between CSF and blood OT levels within individuals; (2) Test whether individual differences in oxytocin levels are associated with individual differences in social functioning, such that children with lower oxytocin levels will exhibit greater social deficits; and (3) Use state-of-the-art mass spectrometry methods to begin to identify novel molecules in CSF that may be associated with social functioning and/or ASD. This research could lead to the discovery of novel biomarkers, implementation of earlier and more accurate diagnostic methods, and the development of drugs that treat the social deficits of ASD.