A novel biochemical model linking dysfunctions in brain melatonin, proopiomelanocortin peptides, and serotonin in autism.

A novel biochemical model for autism is presented, which proposes that a subgroup of autistic individuals may have a hypersecretion of pineal melatonin that produces a cascade of biochemical effects including a corresponding hyposecretion of pituitary proopiomelanocortin (POMC) peptides and a hypersecretion of hypothalamic opioid peptides and serotonin (5-HT). The model is reviewed, and supporting animal and clinical research, is summarized. The first arm of the model suggests that increases in pineal melatonin results in hypersecretion of 5-HT in hypothalamus and blood. The second arm of the model indicates that hypersecretion of melatonin also inhibits the release of hypothalamic corticotrophin-releasing hormone (CRH). Hyposecretion of CRH may result in decreased release of both pituitary B-endorphin (B-E) and adrenocorticotrophin hormone (ACTH); this, in turn, may result in decreased plasma concentrations of B-E, ACTH, and cortisol. In autism, a genetically determined hypersecretion of hypothalamic B-E may further contribute to an inhibition of pituitary B-E because of negative feedback inhibition. Therefore, autism may reflect a dysfunction in the pineal-hypothalamic-pituitary-adrenal axis which, modulates POMC and 5-HT systems of the brain. This model is consistent with numerous clinical investigations implicating hypersecretion of brain 5-HT and opioid peptides in autism. The model may have heuristic importance in guiding future research in the biochemistry of autism.