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

Published online by Cambridge University Press:  01 September 2022

F. Corsi-Zuelli ,
C. Loureiro ,
R. Shuhama ,
D. Quattrone ,
B. Deakin ,
P. Menezes ,
R. Lacchini ,
F. Coeli-Lacchini ,
P. Louzada-Junior  and
C. Del-Ben
F. Corsi-Zuelli*
Affiliation:
University of São Paulo, Ribeirão Preto Medical School, Neuroscience And Behaviour, Ribeirão Preto, Brazil
C. Loureiro
Affiliation:
University of São Paulo, Ribeirão Preto Medical School, Neuroscience And Behaviour, Ribeirão Preto, Brazil
R. Shuhama
Affiliation:
University of São Paulo, Ribeirão Preto Medical School, Neuroscience And Behaviour, Ribeirão Preto, Brazil
D. Quattrone
Affiliation:
King’s College London, Social, Genetic And Developmental Psychiatry Centre, Institute Of Psychiatry, Psychology And Neuroscience, London, United Kingdom
B. Deakin
Affiliation:
University of Manchester, Division Of Neuroscience And Experimental Psychology, Manchester, United Kingdom
P. Menezes
Affiliation:
University of São Paulo, Faculty of Medicine, Department Of Preventive Medicine, São Paulo, Brazil
R. Lacchini
Affiliation:
University of São Paulo, Ribeirão Preto College of Nursing, Brazil, Psychiatric Nursing, Ribeirão Preto, Brazil
F. Coeli-Lacchini
Affiliation:
University of São Paulo, School of Pharmaceutical Sciences, Brazil, Department Of Clinical Analyses, Toxicology And Food Science, Ribeirão Preto, Brazil
P. Louzada-Junior
Affiliation:
University of São Paulo, Ribeirão Preto Medical School, Brazil, Internal Medicine, Ribeirão Preto, Brazil
C. Del-Ben
Affiliation:
University of São Paulo, Ribeirão Preto Medical School, Neuroscience And Behaviour, Ribeirão Preto, Brazil
*
*Corresponding author.

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.

Keywords

PsychosisAdenosineCannabisImmune system
Type
Abstract
Information
European Psychiatry , Volume 65 , Special Issue S1: Abstracts of the 30th European Congress of Psychiatry , June 2022 , pp. S698
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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