Genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Fatty acid amide hydrolase (FAAH) inhibitors are addressed for promising anxiolytics, but human studies on genetically reduced FAAH activity, stress and affective phenotypes are scarce. We investigated the effect of a functional polymorphism of FAAH (FAAH C385A or rs324420; low FAAH activity and high anandamide concentration are associated with the A allele) together with childhood adversity on the anxious and depressive phenotypes in 858 subjects from the general population. Phenotypes were measured by the Zung Self-Rating Depression Scale (ZSDS), the depression and anxiety subscales of the Brief Symptom Inventory (BSI-DEP, BSI-ANX) and the State-Trait Anxiety scales (STAI-S, STAI-T). Childhood Adversity Questionnaire (CHA) was used to assess early life traumas. Frequency of the A allele was greater among subjects with high ZSDS scores compared to the CC genotype. Furthermore, FAAH C385A and the CHA have shown a robust gene-environment interaction, namely, significantly higher anxiety and depression scores were exhibited by individuals carrying the A allele if they had high CHA scores compared to CC carriers. These data provided preliminary evidence that genetically reduced FAAH activity and repetitive stress in the childhood are associated with increased vulnerability for anxiety and depression in later life. Our results together with earlier experimental data suggest that permanently elevated anandamide level together with early life stress may cause a lifelong damage on stress response probably via the downregulation of CB1R during the neurodevelopment in the brain. It may also point to pharmacogenomic consequences, namely ineffectiveness or adverse effects of FAAH inhibitors in this subpopulation.

Original languageEnglish
JournalEuropean Neuropsychopharmacology
DOIs
Publication statusAccepted/In press - Aug 11 2015

Fingerprint

Anxiety
Depression
Wounds and Injuries
Phenotype
Alleles
Gene-Environment Interaction
fatty-acid amide hydrolase
Pharmacogenetics
Anti-Anxiety Agents
Psychological Stress
Gene Frequency
Down-Regulation
Genotype
Equipment and Supplies
Brain
Population
Surveys and Questionnaires

Keywords

  • CB1 receptor
  • Endocannabinoids
  • Epigenetics
  • Neurodevelopment
  • Personalized medicine
  • Pharmacogenomics

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology

Cite this

@article{fe16a0dc574945b98000b7f1b6f6c3e5,
title = "Genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma",
abstract = "Fatty acid amide hydrolase (FAAH) inhibitors are addressed for promising anxiolytics, but human studies on genetically reduced FAAH activity, stress and affective phenotypes are scarce. We investigated the effect of a functional polymorphism of FAAH (FAAH C385A or rs324420; low FAAH activity and high anandamide concentration are associated with the A allele) together with childhood adversity on the anxious and depressive phenotypes in 858 subjects from the general population. Phenotypes were measured by the Zung Self-Rating Depression Scale (ZSDS), the depression and anxiety subscales of the Brief Symptom Inventory (BSI-DEP, BSI-ANX) and the State-Trait Anxiety scales (STAI-S, STAI-T). Childhood Adversity Questionnaire (CHA) was used to assess early life traumas. Frequency of the A allele was greater among subjects with high ZSDS scores compared to the CC genotype. Furthermore, FAAH C385A and the CHA have shown a robust gene-environment interaction, namely, significantly higher anxiety and depression scores were exhibited by individuals carrying the A allele if they had high CHA scores compared to CC carriers. These data provided preliminary evidence that genetically reduced FAAH activity and repetitive stress in the childhood are associated with increased vulnerability for anxiety and depression in later life. Our results together with earlier experimental data suggest that permanently elevated anandamide level together with early life stress may cause a lifelong damage on stress response probably via the downregulation of CB1R during the neurodevelopment in the brain. It may also point to pharmacogenomic consequences, namely ineffectiveness or adverse effects of FAAH inhibitors in this subpopulation.",
keywords = "CB1 receptor, Endocannabinoids, Epigenetics, Neurodevelopment, Personalized medicine, Pharmacogenomics",
author = "J. Laz{\'a}ry and Nora Eszlari and G. Juh{\'a}sz and G. Bagdy",
year = "2015",
month = "8",
day = "11",
doi = "10.1016/j.euroneuro.2016.03.003",
language = "English",
journal = "European Neuropsychopharmacology",
issn = "0924-977X",
publisher = "Elsevier",

}

TY - JOUR

T1 - Genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma

AU - Lazáry, J.

AU - Eszlari, Nora

AU - Juhász, G.

AU - Bagdy, G.

PY - 2015/8/11

Y1 - 2015/8/11

N2 - Fatty acid amide hydrolase (FAAH) inhibitors are addressed for promising anxiolytics, but human studies on genetically reduced FAAH activity, stress and affective phenotypes are scarce. We investigated the effect of a functional polymorphism of FAAH (FAAH C385A or rs324420; low FAAH activity and high anandamide concentration are associated with the A allele) together with childhood adversity on the anxious and depressive phenotypes in 858 subjects from the general population. Phenotypes were measured by the Zung Self-Rating Depression Scale (ZSDS), the depression and anxiety subscales of the Brief Symptom Inventory (BSI-DEP, BSI-ANX) and the State-Trait Anxiety scales (STAI-S, STAI-T). Childhood Adversity Questionnaire (CHA) was used to assess early life traumas. Frequency of the A allele was greater among subjects with high ZSDS scores compared to the CC genotype. Furthermore, FAAH C385A and the CHA have shown a robust gene-environment interaction, namely, significantly higher anxiety and depression scores were exhibited by individuals carrying the A allele if they had high CHA scores compared to CC carriers. These data provided preliminary evidence that genetically reduced FAAH activity and repetitive stress in the childhood are associated with increased vulnerability for anxiety and depression in later life. Our results together with earlier experimental data suggest that permanently elevated anandamide level together with early life stress may cause a lifelong damage on stress response probably via the downregulation of CB1R during the neurodevelopment in the brain. It may also point to pharmacogenomic consequences, namely ineffectiveness or adverse effects of FAAH inhibitors in this subpopulation.

AB - Fatty acid amide hydrolase (FAAH) inhibitors are addressed for promising anxiolytics, but human studies on genetically reduced FAAH activity, stress and affective phenotypes are scarce. We investigated the effect of a functional polymorphism of FAAH (FAAH C385A or rs324420; low FAAH activity and high anandamide concentration are associated with the A allele) together with childhood adversity on the anxious and depressive phenotypes in 858 subjects from the general population. Phenotypes were measured by the Zung Self-Rating Depression Scale (ZSDS), the depression and anxiety subscales of the Brief Symptom Inventory (BSI-DEP, BSI-ANX) and the State-Trait Anxiety scales (STAI-S, STAI-T). Childhood Adversity Questionnaire (CHA) was used to assess early life traumas. Frequency of the A allele was greater among subjects with high ZSDS scores compared to the CC genotype. Furthermore, FAAH C385A and the CHA have shown a robust gene-environment interaction, namely, significantly higher anxiety and depression scores were exhibited by individuals carrying the A allele if they had high CHA scores compared to CC carriers. These data provided preliminary evidence that genetically reduced FAAH activity and repetitive stress in the childhood are associated with increased vulnerability for anxiety and depression in later life. Our results together with earlier experimental data suggest that permanently elevated anandamide level together with early life stress may cause a lifelong damage on stress response probably via the downregulation of CB1R during the neurodevelopment in the brain. It may also point to pharmacogenomic consequences, namely ineffectiveness or adverse effects of FAAH inhibitors in this subpopulation.

KW - CB1 receptor

KW - Endocannabinoids

KW - Epigenetics

KW - Neurodevelopment

KW - Personalized medicine

KW - Pharmacogenomics

UR - http://www.scopus.com/inward/record.url?scp=84962545886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962545886&partnerID=8YFLogxK

U2 - 10.1016/j.euroneuro.2016.03.003

DO - 10.1016/j.euroneuro.2016.03.003

M3 - Article

C2 - 27005594

AN - SCOPUS:84962545886

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

ER -