A possible role of proopiomelanocortin peptides in self-injurious behavior

1. The hypothesis that opioids may be involved in self-injurious behavior is supported by fifteen years of basic animal research suggesting that opioid peptides of the brain and spinal cord participate in the modulation of antinociception in animals, and research of animal models for self-injurious behavior utilizing exogenously administered opiate agonists. 2. Clinical biochemical and pharmacological research conducted over the past five years has also suggested the possibility that opioid peptides may play an important etiological role in the elaboration of self-injurious behavior in some individuals. 3. An opioid overactivity self-injurious hypothesis is supported by results of one study indicating elevated Fraction II opioids (enkephalins) in the lumbar-thecal cerebrospinal fluid of self-injurious children compared to controls, and by the five out of six published studies demonstrating statistically significant decreases in the frequency of self-injurious behavior with the opiate antagonist, naltrexone. 4. A very recent investigation has suggested that some self-injurious individuals show abnormalities in their plasma proopiomelanocortin peptide response to naltrexone, thereby indicating a possible dysfunction in the responsitivity of the proopiomelanocortin system of the hypothalamic-pituitary-adrenal axis of these individuals. 5. These data and results of other investigations have resulted in the elaboration of the original opioid hypothesis to a more comprehensive biochemical model that focuses on this proopiomelanocortin dysregulation. 6. Because of biochemical and functional interrelationships between proopiomelanocortin peptides and certain other neurochemical systems in the brain, it is proposed that pineal melatonin and serotonin may also be involved in this dysregulation. Further basic and clinical research will be needed to test the proposed biochemical model for self-injurious behavior.