A functional variant of CB2 receptor gene interacts with childhood trauma and FAAH gene on anxious and depressive phenotypes

J. Lazáry, Nora Eszlari, G. Juhász, Gyorgy Bagdy

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Accumulating data suggest that CB2 receptor plays a crucial role in development of anxiety via regulatory function of stress response and neuroimmune crosstalk. Although animal experiments confirm this relationship, relevant human genetic studies on CB2 receptor gene (CNR2) in association with affective phenotype are absent. METHODS: CNR2 R63Q and FAAH C385A functional polymorphisms were genotyped of 921 volunteers from the general population. Phenotypic variables were measured by the Zung Self-related Depression Scale (ZSDS), The State-Trait Anxiety Inventory (Trait subscale, STAI-T) and the depressive and anxious subscales of the Brief Symptom Inventory (BSI-DEP and BSI-ANX). Early life trauma was assesssed by the Childhood Trauma Questionnaire (CHQ). Using general linear models we tested possible associations between phenotypic variance and genotype distribution. RESULTS: There was a significant main effect of RR genotype of R63Q on ZSDS score (p = 0.007) and a remarkble interacting effect of CHQ and R63Q on scores of ZSDS, STAI-T and BSI-ANX scales (p = 0.009; p = 0.003; p = 0.001; respectively). R allele of R63Q and A allele of FAAH C385A were associated with significantly higher ZSDS, STAI-T and BSI-ANX scores compared to non-risk allele carriers (p = 0.009; p = 0.007; p = 0.007, respectively). The highest phenotypic scores were observed in GxGxE model (pZSDS = 0.04; pBSI-DEP = 0.006; pSTAI-T = 0.001; pBSI-ANX = 3.8 × 10-5). CONCLUSIONS: In this first human genetic study on CNR2 and childhood trauma we revealed that dysfunctional CB2 receptor and FAAH can contribute to greater sensitivity for childhood trauma possibly via weaker inhibiton of inflammatory and overactivated HPA axis.

Original languageEnglish
Pages (from-to)716-722
Number of pages7
JournalJournal of affective disorders
Volume257
DOIs
Publication statusPublished - Oct 1 2019

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Cannabinoid Receptor CB2
Cannabinoid Receptors
Endocannabinoids
Phenotype
Depression
Wounds and Injuries
Genes
Alleles
Medical Genetics
Anxiety
Genotype
Equipment and Supplies
Volunteers
Linear Models
Population

Keywords

  • Cannabinoid type 2 receptor
  • CNR2
  • Endocannabinoid
  • GxE interaction
  • GxG interaction
  • GxGxE interaction

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

A functional variant of CB2 receptor gene interacts with childhood trauma and FAAH gene on anxious and depressive phenotypes. / Lazáry, J.; Eszlari, Nora; Juhász, G.; Bagdy, Gyorgy.

In: Journal of affective disorders, Vol. 257, 01.10.2019, p. 716-722.

Research output: Contribution to journalArticle

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AU - Juhász, G.

AU - Bagdy, Gyorgy

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N2 - BACKGROUND: Accumulating data suggest that CB2 receptor plays a crucial role in development of anxiety via regulatory function of stress response and neuroimmune crosstalk. Although animal experiments confirm this relationship, relevant human genetic studies on CB2 receptor gene (CNR2) in association with affective phenotype are absent. METHODS: CNR2 R63Q and FAAH C385A functional polymorphisms were genotyped of 921 volunteers from the general population. Phenotypic variables were measured by the Zung Self-related Depression Scale (ZSDS), The State-Trait Anxiety Inventory (Trait subscale, STAI-T) and the depressive and anxious subscales of the Brief Symptom Inventory (BSI-DEP and BSI-ANX). Early life trauma was assesssed by the Childhood Trauma Questionnaire (CHQ). Using general linear models we tested possible associations between phenotypic variance and genotype distribution. RESULTS: There was a significant main effect of RR genotype of R63Q on ZSDS score (p = 0.007) and a remarkble interacting effect of CHQ and R63Q on scores of ZSDS, STAI-T and BSI-ANX scales (p = 0.009; p = 0.003; p = 0.001; respectively). R allele of R63Q and A allele of FAAH C385A were associated with significantly higher ZSDS, STAI-T and BSI-ANX scores compared to non-risk allele carriers (p = 0.009; p = 0.007; p = 0.007, respectively). The highest phenotypic scores were observed in GxGxE model (pZSDS = 0.04; pBSI-DEP = 0.006; pSTAI-T = 0.001; pBSI-ANX = 3.8 × 10-5). CONCLUSIONS: In this first human genetic study on CNR2 and childhood trauma we revealed that dysfunctional CB2 receptor and FAAH can contribute to greater sensitivity for childhood trauma possibly via weaker inhibiton of inflammatory and overactivated HPA axis.

AB - BACKGROUND: Accumulating data suggest that CB2 receptor plays a crucial role in development of anxiety via regulatory function of stress response and neuroimmune crosstalk. Although animal experiments confirm this relationship, relevant human genetic studies on CB2 receptor gene (CNR2) in association with affective phenotype are absent. METHODS: CNR2 R63Q and FAAH C385A functional polymorphisms were genotyped of 921 volunteers from the general population. Phenotypic variables were measured by the Zung Self-related Depression Scale (ZSDS), The State-Trait Anxiety Inventory (Trait subscale, STAI-T) and the depressive and anxious subscales of the Brief Symptom Inventory (BSI-DEP and BSI-ANX). Early life trauma was assesssed by the Childhood Trauma Questionnaire (CHQ). Using general linear models we tested possible associations between phenotypic variance and genotype distribution. RESULTS: There was a significant main effect of RR genotype of R63Q on ZSDS score (p = 0.007) and a remarkble interacting effect of CHQ and R63Q on scores of ZSDS, STAI-T and BSI-ANX scales (p = 0.009; p = 0.003; p = 0.001; respectively). R allele of R63Q and A allele of FAAH C385A were associated with significantly higher ZSDS, STAI-T and BSI-ANX scores compared to non-risk allele carriers (p = 0.009; p = 0.007; p = 0.007, respectively). The highest phenotypic scores were observed in GxGxE model (pZSDS = 0.04; pBSI-DEP = 0.006; pSTAI-T = 0.001; pBSI-ANX = 3.8 × 10-5). CONCLUSIONS: In this first human genetic study on CNR2 and childhood trauma we revealed that dysfunctional CB2 receptor and FAAH can contribute to greater sensitivity for childhood trauma possibly via weaker inhibiton of inflammatory and overactivated HPA axis.

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