It remains a mysterious problem with enormous economic and management complications. There are no known causes or treatments for SIB. Recent evidence has implicated the endogenous opiate system, specifically B- endorphin (BE), in this aberrant behavior. The most compelling evidence supporting the opiate hypothesis is that challenge with opiate blockers decreased SIB in mentally retarded patients. In the first direct test of the opiate hypothesis, blood levels of BE, but not related peptides, were elevated immediately after an SIB episode. Most significantly, patients with the largest change in BE after SIB were the most positive responders to opiate blockers. The major objective of the proposed project is to replicate and extend these new observations, to determine if BE is a specific biological marker for forms of SIB and determine if changes in BE after SIB predict response to treatment. The primary hypothesis is that SIB results from disturbance of the opiate system manifested by, 1) unique and specific release of BE after SIB and, 2) sensitivity of the opiate receptor to opiate blockers. This hypothesis will be tested in sixty four mentally-retarded clients (n=16/group) with SIB or agitated behavior (AB) in a five phase study. Candidate clients will be identified and characterized by intensive behavioral observation in the first two phases. During the third phase, blood will be collected immediately after SIB or AB and analyzed for BE and the related peptides, ACTH and CRH. In phase four, response of clients will be evaluated to acute challenge with three doses of an opiate blocker, naltrexone (NTX). Response to long-term challenge (nine to twenty-one months) with NTX will comprise phase five. Results will be analyzed to; 1) determine the relationship between BE release after SIB and response to NTX and, 2) determine the unique contribution of BE to SIB.
