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
Department of Neuroscience and Behaviour, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Center for Research on Inflammatory Diseases - CRID, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Psychol Med. 2021 Mar 19:1-11. doi: 10.1017/S0033291721000726.
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.
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)-1β, IL-6, IL-4, IL-10, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β); 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.
Mediation: Cannabis consumption was not associated with increased inflammation, thus not supporting a mediating effect of inflammation. Moderation: Daily use and age of onset <17 interacted significantly with the ICS to increase the odds of psychosis beyond their individual effects and were only associated with psychosis among those scoring medium-high in the ICS.
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.
吸食大麻是与精神病相关的一个可改变的风险因素，但并非所有大麻使用者都会患上精神病。动物研究表明，先前活跃的免疫系统与随后接触大麻相互作用，并调节大麻与精神病之间的关联，支持双打击假说。临床研究较少，尚不清楚免疫系统是否是调节大麻与精神病关联的生物学因素，或者大麻是否会增加炎症，进而增加患精神病的可能性。
我们使用PROCESS宏程序探讨血液炎症的中介和调节作用。我们使用了一项横断面研究的数据，包括153名首发精神病患者和256名社区对照。参与者回答了大麻使用经历问卷（大麻使用频率、开始使用年龄和使用时长），并测量了血浆细胞因子[白细胞介素（IL）-1β、IL-6、IL-4、IL-10、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、转化生长因子-β（TGF-β）；多重检测]。我们计算了一个炎症综合评分（ICS）来代表全身炎症状态。混杂因素包括性别、年龄、种族、教育水平、体重指数、吸烟情况、其他药物的终身使用情况以及抗精神病治疗情况。
中介作用：吸食大麻与炎症增加无关，因此不支持炎症的中介作用。调节作用：每日使用大麻且开始使用年龄<17岁与ICS显著相互作用，增加了患精神病的几率，超出了它们各自的影响，并且仅与ICS中得分中等偏高的人群中的精神病相关。
免疫失调可能是精神病病理生理学的一部分，不能用大麻使用或其他混杂因素来解释。我们提供了首个初步证据，证明免疫失调会改变大麻与精神病之间的关联，这与双打击假说一致。
