Immune regulatory gene polymorphisms, frequent cannabis use, and psychosis: implications to Treg hypofunction
Fabiana Corsi-Zuelli, C. Loureiro, Rosana Shuhama, Diego Quattrone, B. Deakin, P. Menezes, R. Lacchini, F. Coeli-Lacchini, Paulo Louzada-Junior, C. Del-Ben
European Psychiatry June 1, 2022 DOI: 10.1192/j.eurpsy.2022.1798 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case-control genetic association study Peer reviewed |
|---|---|
| Sample size | 423 |
| Population | 283 community-based controls and 140 recent-onset psychosis patients in Ribeirão Preto, Brazil (EU-GEI consortium) |
| Measures | Cannabis Experience Questionnaire |
| Topics | Cannabis |
| Key findings | The authors report that polymorphisms in ENTPD1, NT5E, and FOXP1 moderated the association between cannabis use and psychosis: among carriers of the variant/heterozygous genotypes, less-than-daily use was associated with about 3-fold higher odds of psychosis and daily use with roughly 14- to 21-fold higher odds, in a dose-response pattern. They suggest this is consistent with a regulatory T-cell hypofunction hypothesis. |
Abstract
Introduction: We have previously shown that the association between frequent cannabis use and psychosis is more likely in subgroups with low-grade inflammation than subgroups without (PMID: 33736715). The role of immune-related polymorphisms remains unknown.
Objectives: To explore whether polymorphisms affecting the function of key immune regulatory proteins moderate the association between cannabis and psychosis, namely: ENTPD1 and NT5E, involved in the synthesis of CD39, CD73, respectively, and anti-inflammatory adenosine; CTLA4 and FOXP1, essential for Treg functional capacity.
Methods: We genotyped blood samples from 283 community-based controls and 140 recent-onset psychosis patients in Brazil (EU-GEI consortium, Ribeirão Preto/SP) for twelve polymorphisms (ENTPD1: rs3814159, rs3176891, rs10748643; NT5E: rs9444348, rs2295890; CTLA4: rs3087243, rs231775, rs5742909, rs4553808; FOXP1: rs6803008, rs6786408, rs830599; Illumina Human Core Exome-24). Cannabis frequency (daily, less than daily, never) was assessed by self-report (Cannabis Experience Questionnaire). Binary logistic regression models (OR,95%CI) included case status as the outcome, genotype (dominant model), cannabis frequency, and an interaction term between the two as exposure, adjusting for confounders (age, sex, ethnicity, tobacco smoking).
Results: We found significant interactions between cannabis use and polymorphisms for ENTPD1 (rs3814159), NT5E (rs9444348), and FOXP1 (rs6786408). Less than daily or daily use were, in a dose-response fashion, only associated with psychosis in those with the variant and heterozygous genotypes; less than daily: ENTPD1 AG/GG (3.34,1.71-6.50); NT5E AG/AA (3.71,1.87-7.33); FOXP1 AC/CC (2.98,1.54-5.77); daily: ENTPD1 AG/GG (16.81;5.89-47.96); NT5E AG/AA (21.20,6.81-66.01); FOXP1 AC/CC (13.75,5.22-36.21).
Conclusions: Variation in genes that affect Treg function appears to modify the effect of cannabis consumption on psychosis in keeping with Treg hypofunction hypothesis (PMID:33713699). Disclosure No significant relationships.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |