Biobehavioral Interactions between Endocannabinoid and Hypothalamicpituitary- adrenal Systems in Psychosis: A Systematic Review

Abstract

Background: The diathesis-stress paradigm and the cannabinoid-hypothesis have been proposed as possible pathophysiological models of schizophrenia. However, they have historically been studied independently of each other. Objective: This PRISMA 2020-compliant systematic review aimed at reappraising the interplay be- tween the hypothalamic-pituitary-adrenal (HPA) axis and the endocannabinoid (eCB) system in psy- chosis-spectrum disorder risk and outcome. Methods: All pathophysiological and outcome clinical studies, concomitantly evaluating the two sys- tems in psychosis-spectrum disorder risk and different stages of illness, were gathered from electronic databases (Pubmed, Web of Science, and Scopus), and discussed. Results: 41 eligible outputs were extracted, focusing on at least a biological measure (9 HPA-related studies: 4 eCB-interventional, 1 HPA-interventional, 1 both HPA-interventional and non-interventional, 3 non-interventional; 2 eCB-related studies: non-interventional), environmental measures only (29 studies: 1 eCB- interventional, 28 non-interventional), and genetic measures (1 study: non-interventional). In- dependent contributions of aberrancies in the two systems to the physiopathology and outcome of psy- chosis were confirmed. Also, concomitant alterations in the two systems, either genetically defined (e.g., CNR1 genetic variation), biologically determined (e.g., dysfunctional HPA axis or endocanna- binoid signaling), or behaviorally imputed (e.g., cannabis use, stress exposure, and response), were consistently reported in psychosis. Further, a complex biobehavioral perturbation was revealed not on- ly within each system (e.g., cannabis use affecting the eCB tone, stress exposure affecting the HPA ax- is), but also across the two systems (e.g., THC affecting the HPA axis, childhood trauma affecting the endocannabinoid signaling). Conclusion: There is a need to concomitantly study the two systems’ mechanistic contribution to psychosis in order to establish more refined biological relevance.

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

“…A role for psychological mechanisms was questioned, including insecure attachment styles, dysfunctional cognitive schemas, thinking errors, and non-psychotic symptoms (Appiah-Kusi et al, 2017;Bebbington, 2015;Rafiq et al, 2018). Moreover, a growing body of research has explored several potential biological underpinnings (Davies et al, 2022;Di Nicola et al, 2013;Egerton et al, 2016;Howes & Murray, 2014;Pruessner et al, 2017;Selten et al, 2013), accounting for the association between psychosocial stressors and psychosis, as well as the interacting or mediating role of other risk factors (e.g., cannabis use) (Arranz et al, 2018;Colizzi, Bortoletto et al, 2023). Interestingly, individuals with ASD were found to experience more psychosocial stressors over the course of their lives (e.g., family poverty, sexual abuse, parental illness, parental alcoholism, and parental divorce) compared with neurotypical individuals (Berg et al, 2016;Berg et al, 2018;Hoover & Kaufman, 2018;Schneider et al, 2019).…”

Thematic Selection: Stress and Stress-related Disorders Developmental and Neuroendocrine Aspects of Stress and Stress-related Disorders (Part 1)

“…Hodes et al [ 25 ] provide an expert review on the very important and often neglected topic of gender-related differences in stress response mechanisms. The next two articles by Kulakova et al [ 26 ] and Colizzi et al [ 27 ] investigate the interaction between the HPA axis and social cognition as well as the endocannabinoid system in the examples of borderline personality disorder and psychosis, respectively. Finally, Bendau et al [ 28 ] review the neuroendocrine mechanisms and the treatment effects of exercise in different stress-related disorders [ 28 ].…”