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The Autism–Psychosis Continuum Conundrum: Exploring the Role of the Endocannabinoid System

Research output: Contribution to journalReview articlepeer-review

Marco Colizzi, Riccardo Bortoletto, Rosalia Costa, Sagnik Bhattacharyya, Matteo Balestrieri

Original languageEnglish
Article number5616
JournalInternational Journal of Environmental Research and Public Health
Issue number9
Published1 May 2022

Bibliographical note

Funding Information: The authors would like to acknowledge infrastructure from the Integrated University Hospital of Verona and the University of Udine. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

King's Authors


Evidence indicates shared physiopathological mechanisms between autism and psychosis. In this regard, the endocannabinoid system has been suggested to modulate neural circuits during the early stage of neurodevelopment, with implications for both autism and psychosis. Nevertheless, such potential common markers of disease have been investigated in both autism and psychosis spectrum disorders, without considering the conundrum of differentiating the two groups of conditions in terms of diagnosis and treatment. Here, we systematically review all human and animal studies examining the endocannabinoid system and its biobehavioral correlates in the association between autism and psychosis. Studies indicate overlapping biobehavioral aberrancies between autism and schizophrenia, subject to correction by modulation of the endocannabinoid system. In addition, common cannabinoid-based pharmacological strategies have been identified, exerting epigenetic effects across genes controlling neural mechanisms shared between autism and schizophrenia. Interestingly, a developmental and transgenerational trajectory between autism and schizophrenia is supported by evidence that exogenous alteration of the endocannabinoid system promotes progression to inheritable psychosis phenotypes in the context of biobehavioral autism vulnerability. However, evidence for a diametral association between autism and psychosis is scant. Several clinical implications follow from evidence of a developmental continuum between autism and psychosis as a function of the endocannabinoid system dysregulation.

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