Abstract

Autism is a collection of disorders or subtypes with distinctive or prominent phenotypes and genotypes. The study of adults with autism offers a unique opportunity to examine its phenotypic diversity. Recent evidence has identified disturbances in specific neurochemical systems that are associated with primary autistic symptoms. Establishing biological markers, such as specific neurochemical disturbances, not only confers greater precision in phenotyping individuals but also provides the basis for rational intervention. Our initial studies in adult individuals exhibiting self- injurious behavior generated evidence that the proopiomelanocortin system, specifically the endogenous opioid system, may be disregulated in subgroups of autistic patients. These findings, corroborated in at least 15 other laboratories, indicated that treatment with an opiate blocker, naltrexone, reduced SIB in 30-70% of individuals observed. However, the effects of NTX on SIB were not simple. We and others have found that concentration of plasma POMC fragments, specifically opioid fragments, contributed to the symptoms of autism and to the response to treatment. Uncoupling of the release of POMC products predicted the efficacy of NTX treatment on the expression of SIB. Uncoupling of POMC fragments among autistic and SIB patients suggested a basic, underlying defect, perhaps in the POMC gene. The findings of a maternal influence on the C-terminal BE fragment among individuals with autism and our preliminary findings, reported here, of a mutation in the opioid region of the POMC gene in an autistic individual, were consistent with the prospect that a subgroup of patients will be identified who share a POMC genetic defect.