The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis

Author(s)

Corsi-Zuelli, Fabiana ; Marques, Leonardo ; da Roza, Daiane Leite ; Loureiro, Camila Marcelino ; Shuhama, Rosana ; Di Forti, Marta ; Menezes, Paulo Rossi ; Louzada-Junior, Paulo ; Del-Ben, Cristina Marta

• Document type: Journal article
• Source: PSYCHOLOGICAL MEDICINE; v. N/A, p. 11-pg., 2021-03-19.

Abstract

Background Cannabis consumption is a modifiable risk factor associated with psychosis, but not all cannabis users develop psychosis. Animal studies suggest that an antecedent active immune system interacts with subsequent cannabis exposure and moderates the cannabis-psychosis association, supporting the two-hit hypothesis. The clinical investigations are few, and it is unclear if the immune system is a biological candidate moderating the cannabis-psychosis association or whether cannabis increases inflammation, which in turn, augments psychosis likelihood. Methods We explored the mediating and moderating role of blood inflammation using PROCESS macro. We used data from a cross-sectional study, including 153 first-episode psychosis patients and 256 community-based controls. Participants answered the Cannabis Experience Questionnaire (cannabis frequency, age of onset, and duration), and plasma cytokines were measured [interleukin (IL)-1 beta, IL-6, IL-4, IL-10, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta); multiplex]. We computed an inflammatory composite score (ICS) to represent the systemic inflammatory state. Confounders included sex, age, ethnicity, educational level, body mass index, tobacco smoking, lifetime use of other drugs, and antipsychotic treatment. Results Mediation: Cannabis consumption was not associated with increased inflammation, thus not supporting a mediating effect of inflammation. Moderation: Daily use and age of onset Conclusions Immune dysregulation might be part of the pathophysiology of psychosis, not explained by cannabis use or other confounders. We provide the first and initial evidence that immune dysregulation modifies the cannabis-psychosis association, in line with a two-hit hypothesis. (AU)

• FAPESP's process: 12/05178-0 - Schizophrenia and other psychotic disorders: social and biological determinants
• Grantee: Paulo Rossi Menezes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/13353-0 - Association between inflammation and use of cannabis (Cannabis sativa) in patients in first psychotic episode
• Grantee: Leonardo Marques
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/11167-3 - Gene-environment interactions in Schizophrenia and other psychotic disorders
• Grantee: Rosana Shuhama
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/13229-2 - Inflammatory profile in the general population: transdiagnostic dimensions in the context of the psychosis continuum
• Grantee: Fabiana Maria das Graças Corsi Zuelli
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/07581-2 - Mortality in mental disorders with recent onset psychotic manifestations
• Grantee: Daiane Leite da Roza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral