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

  • Ronald S. Chamberlain
    Affiliations
    Brain Research Central and the Department of Pschiatry at Children's National Medical Center and the Departments of Psychiatry and Behavioral Sciences and Pediatrics at George Washington University School of Medicine, USA
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  • Barbara H. Herman
    Correspondence
    Address reprint requests to Dr. Barbara H. Herman, Brain Research Center, Children's National Medical Center, 111 Michigan Avenue, N.W., Washington, D.C. 20010 USA.
    Affiliations
    Brain Research Central and the Department of Pschiatry at Children's National Medical Center and the Departments of Psychiatry and Behavioral Sciences and Pediatrics at George Washington University School of Medicine, USA
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      Abstract

      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 clinic 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 adrenocorticotropin 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 is autism. The model may have heuristic importance in guiding future research in the biochemistry of autism.
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