Event-related desynchronization and visual orientational behavior were examined in 2 autistic boys to determine if blockade of endogenous opioid activity facilitates cognitive processing at a cortical level. Before naltrexone, the boys showed no selective alpha blocking during exposure to either mother’s pictures or white light. Unlike normals, they exhibited strong alpha band enhancement at temporocentral recording sites. Two hours after administering 0.5 mg/kg naltrexone, mother- as well as light-related alpha blocking appeared at occipital, occipitotemporal, and prefrontal sites. These effects were gone 24 h after dosing in one child, but persisted in the other. A parallel increase in visual pursuit in a social context was observed. These results affirm that autistic gaze aversion can be caused by excessive opioid activity interfering with corticothalamocortical processing of visual stimuli.

The effect of month-long naltrexone (NTX) treatment at a daily oral dose of 0.5 mg/kg/day was contrasted with placebo (PLC) in a double-blind study with conjoint clinical and biochemical evaluations of therapeutic effects. Modest clinical benefits were achieved with both PLC and NTX, with marginally better overall results following NTX, and degree of improvement appeared to be related to plasma chemical profiles. Massively elevated levels of β-endorphin were observed in all children with assays using C-terminal antibody but not with an N-terminal antibody assay. In addition, 70% of the children exhibited abnormally low levels of adrenocorticotropic hormone, and smaller subsets exhibited elevated norepinephrine (60%), arginine-vasopressin (50%), and serotonin (20%). The best clinical responders exhibited the clearest normalization of the elevated plasma chemistries, especially in C-terminal-β-endorphin and serotonin. There was some evidence of therapeutic carry-over effects in both clinical and biochemical measures in those children who received NTX before PLC. The results suggest that NTX only benefits a subgroup of autistic children, who may be identified by the presence of certain plasma abnormalities. These results suggest a possible linkage between abnormal plasma chemistries, especially those related to the pro-opiomelanocortin system, and autistic symptoms.

Recent evidence suggests the presence of opioid dysregulation in autistic disorders. The utility of naltexone therapy is summarized and preliminary evidence for abnormal plama carboxy-terminal β-endorphin, AVP, ACTH, NE & 5-HT levels as markers of the disorder.

BOUVARD, M. P.*; LEBOYER, M.*; LAUNAY, J. M.*; RECASENS, C.*; WALLER, D.*; PLUMET, M. H.*; TABUTEAU, F.**; DUGAS, M.*; LENSING, P.*; PANKSEPP, J.* Author Information

The neurobiological rationale for an opiate antagonist pharmacotherapy of autism is presented. Naltrexone efficacy in decreasing autistic behaviour and in increasing social-affiliative behaviour was explored in a 5-year-old autistic boy. Naltrexone (0.5 mg/kg 3 times peer week) was effective in immediately decreasing gross motor activity and stereotyped behaviour and caused a delayed increase of crying, smiling and rough-and-tumble play. This single case presents preliminary evidence that a therapeutically valuable rebound reaction is possible and that the human opioid system modulates social-affective processes. The possibility of psychological factors being instrumental in achieving this effect is discussed as being suitable for future clinical trials.