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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: PSYCHOLOGICAL MEDICINE; v. N/A, p. 11-pg., 2021-03-19.

Resumo

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)

• Processo FAPESP: 12/05178-0 - Esquizofrenia e outros transtornos psicóticos: determinantes sociais e biológicos
• Beneficiário: Paulo Rossi Menezes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/13353-0 - Associação entre inflamação e uso de maconha (Cannabis sativa) em pacientes em primeiro episódio psicótico (PEP)
• Beneficiário: Leonardo Marques
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 13/11167-3 - Interações genético-ambientais na Esquizofrenia e outros transtornos psicóticos
• Beneficiário: Rosana Shuhama
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 19/13229-2 - Perfil inflamatório na população geral: evidência dimensional transdiagnóstica no contexto do continuum das psicoses
• Beneficiário: Fabiana Maria das Graças Corsi Zuelli
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/07581-2 - Mortalidade em transtornos mentais com manifestações psicóticas de início recente
• Beneficiário: Daiane Leite da Roza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado