Elsevier

Biological Psychiatry

Volume 28, Issue 9, 1 November 1990, Pages 773-793
Biological Psychiatry

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

https://doi.org/10.1016/0006-3223(90)90513-2Get rights and content

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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    ☆

    Supported in part by grants from NICHD-HD23330-01, Food and Drug Administrartion Orphan Drug Grant, March of Dimes Birth Defects Social and Behavioural Sciences Research Grant (12-235), the Stallone Fund for Autism Research, the Board of Lady Visitors of Children's National Medical Center, and the Adrianna Foundation (awarded to B.H.H.. R.S.C. is a recipient of a W.T. Gill Research felloship awarad from George Washington University School of Medicine and a fellowship from the Summer Science Research Programa for Medical Students Grant 8-88-48 from the March of Dimes Birth Defects Foundations.

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