European Psychiatry (Jun 2022)

Immune regulatory gene polymorphisms, frequent cannabis use, and psychosis: implications to Treg hypofunction

  • F. Corsi-Zuelli,
  • C. Loureiro,
  • R. Shuhama,
  • D. Quattrone,
  • B. Deakin,
  • P. Menezes,
  • R. Lacchini,
  • F. Coeli-Lacchini,
  • P. Louzada-Junior,
  • C. Del-Ben

DOI
https://doi.org/10.1192/j.eurpsy.2022.1798
Journal volume & issue
Vol. 65
pp. S698 – S698

Abstract

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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.

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