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

Abstract

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.

Risk of psychosis in autism spectrum disorder individuals exposed to psychosocial stressors: A 9‐year chart review study

“…Non‐affective (e.g., schizophrenia) and affective psychoses (e.g., bipolar disorder with psychotic features) may be regarded as part of a developmental trajectory also embracing autism spectrum disorder (ASD) and other neurodevelopmental conditions arising earlier in life (Owen & O'Donovan, 2017). The significant clinical comorbidity between these conditions (Hossain et al, 2020; Varcin et al, 2022), the emerging evidence of shared genetic background between psychoses and ASD (Craddock & Owen, 2010; Owen & O'Donovan, 2017), and the presence of common environmental risk factors impacting early brain development (Bortoletto & Colizzi, 2022; Colizzi et al, 2022; Howes & Murray, 2014; Owen et al, 2016; Owen & O'Donovan, 2017) strengthen the paradigm of an etiological and neurodevelopmental continuum model. Importantly, increasing psychosis rates and clinical high risk for psychosis (CHR‐P) states have been reported among autistic individuals (Foss‐Feig et al, 2019; Gadow, 2012; Selten et al, 2015).…”

Cannabis Use in Autism: Reasons for Concern about Risk for Psychosis

“…To further explore the above-mentioned neurodevelopmental continuum paradigm, we recently conducted a systematic review aimed at investigating the puzzling connection between autism and psychosis through the contribution of endocannabinoid (eCB) system modulation [ 14 ]. Overall, evidence from preclinical and clinical studies included in the systematic analysis converges on an overlapping relationship between autism and psychosis [ 15 , 16 ], with a potential developmental trajectory from autism to psychosis as a function of the eCB system disruption.…”

Autism Spectrum as an Etiologic Systemic Disorder: A Protocol for an Umbrella Review

“…The endocannabinoid system is a hot topic on mental disorders pathways; an interesting review indicates overlapping bio-behavioural aberrancies between autism and schizophrenia. In addition, common cannabinoid-based pharmacological strategies have been identified, exerting epigenetic effects across genes and controlling neural mechanisms [ 29 ].…”