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

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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
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: PSYCHOLOGICAL MEDICINE; v. N/A, p. 11-pg., 2021-03-19.

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