CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms

G. Juhász, Diana Chase, Emma Pegg, Darragh Downey, Zoltan G. Toth, Kathryn Stones, Hazel Platt, Krisztina Mekli, Antony Payton, Rebecca Elliott, Ian M. Anderson, J. F William Deakin

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Cannabinoid receptor 1 (CB1) gene (CNR1) knockout mice are prone to develop anhedonic and helpless behavior after chronic mild stress. In humans, the CB1 antagonist rimonabant increases the risk of depressed mood disorders and anxiety. These studies suggest the hypothesis that genetic variation in CB1 receptor function influences the risk of depression in humans in response to stressful life events. In a population sample (n = 1269), we obtained questionnaire measures of personality (Big Five Inventory), depression and anxiety (Brief Symptom Inventory), and life events. The CNR1 gene was covered by 10 SNPs located throughout the gene to determine haplotypic association. Variations in the CNR1 gene were significantly associated with a high neuroticism and low agreeableness phenotype (explained variance 1.5 and 2.5%, respectively). Epistasis analysis of the SNPs showed that the previously reported functional 5′ end of the CNR1 gene significantly interacts with the 3′ end in these phenotypes. Furthermore, current depression scores significantly associated with CNR1 haplotypes but this effect diminished after covariation for recent life events, suggesting a gene × environment interaction. Indeed, rs7766029 showed highly significant interaction between recent negative life events and depression scores. The results represent the first evidence in humans that the CNR1 gene is a risk factor for depression - and probably also for co-morbid psychiatric conditions such as substance use disorders - through a high neuroticism and low agreeableness phenotype. This study also suggests that the CNR1 gene influences vulnerability to recent psychosocial adversity to produce current symptoms of depression.

Original languageEnglish
Pages (from-to)2019-2027
Number of pages9
JournalNeuropsychopharmacology
Volume34
Issue number8
DOIs
Publication statusPublished - Jul 2009

Fingerprint

Depression
Genes
Cannabinoid Receptors
rimonabant
Phenotype
Single Nucleotide Polymorphism
Anxiety
Cannabinoid Receptor Antagonists
Equipment and Supplies
Gene-Environment Interaction
Gene Knockout Techniques
Mood Disorders
Knockout Mice
Haplotypes
Substance-Related Disorders
Psychiatry
Personality
Neuroticism
Population

Keywords

  • CNR1
  • Depression
  • Epistasis
  • Gene × environment interaction
  • Haplotype
  • Personality

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms. / Juhász, G.; Chase, Diana; Pegg, Emma; Downey, Darragh; Toth, Zoltan G.; Stones, Kathryn; Platt, Hazel; Mekli, Krisztina; Payton, Antony; Elliott, Rebecca; Anderson, Ian M.; Deakin, J. F William.

In: Neuropsychopharmacology, Vol. 34, No. 8, 07.2009, p. 2019-2027.

Research output: Contribution to journalArticle

Juhász, G, Chase, D, Pegg, E, Downey, D, Toth, ZG, Stones, K, Platt, H, Mekli, K, Payton, A, Elliott, R, Anderson, IM & Deakin, JFW 2009, 'CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms', Neuropsychopharmacology, vol. 34, no. 8, pp. 2019-2027. https://doi.org/10.1038/npp.2009.19
Juhász, G. ; Chase, Diana ; Pegg, Emma ; Downey, Darragh ; Toth, Zoltan G. ; Stones, Kathryn ; Platt, Hazel ; Mekli, Krisztina ; Payton, Antony ; Elliott, Rebecca ; Anderson, Ian M. ; Deakin, J. F William. / CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms. In: Neuropsychopharmacology. 2009 ; Vol. 34, No. 8. pp. 2019-2027.
@article{5e56ba5de9a04e5b90dcdf43f316f6cd,
title = "CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms",
abstract = "Cannabinoid receptor 1 (CB1) gene (CNR1) knockout mice are prone to develop anhedonic and helpless behavior after chronic mild stress. In humans, the CB1 antagonist rimonabant increases the risk of depressed mood disorders and anxiety. These studies suggest the hypothesis that genetic variation in CB1 receptor function influences the risk of depression in humans in response to stressful life events. In a population sample (n = 1269), we obtained questionnaire measures of personality (Big Five Inventory), depression and anxiety (Brief Symptom Inventory), and life events. The CNR1 gene was covered by 10 SNPs located throughout the gene to determine haplotypic association. Variations in the CNR1 gene were significantly associated with a high neuroticism and low agreeableness phenotype (explained variance 1.5 and 2.5{\%}, respectively). Epistasis analysis of the SNPs showed that the previously reported functional 5′ end of the CNR1 gene significantly interacts with the 3′ end in these phenotypes. Furthermore, current depression scores significantly associated with CNR1 haplotypes but this effect diminished after covariation for recent life events, suggesting a gene × environment interaction. Indeed, rs7766029 showed highly significant interaction between recent negative life events and depression scores. The results represent the first evidence in humans that the CNR1 gene is a risk factor for depression - and probably also for co-morbid psychiatric conditions such as substance use disorders - through a high neuroticism and low agreeableness phenotype. This study also suggests that the CNR1 gene influences vulnerability to recent psychosocial adversity to produce current symptoms of depression.",
keywords = "CNR1, Depression, Epistasis, Gene × environment interaction, Haplotype, Personality",
author = "G. Juh{\'a}sz and Diana Chase and Emma Pegg and Darragh Downey and Toth, {Zoltan G.} and Kathryn Stones and Hazel Platt and Krisztina Mekli and Antony Payton and Rebecca Elliott and Anderson, {Ian M.} and Deakin, {J. F William}",
year = "2009",
month = "7",
doi = "10.1038/npp.2009.19",
language = "English",
volume = "34",
pages = "2019--2027",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms

AU - Juhász, G.

AU - Chase, Diana

AU - Pegg, Emma

AU - Downey, Darragh

AU - Toth, Zoltan G.

AU - Stones, Kathryn

AU - Platt, Hazel

AU - Mekli, Krisztina

AU - Payton, Antony

AU - Elliott, Rebecca

AU - Anderson, Ian M.

AU - Deakin, J. F William

PY - 2009/7

Y1 - 2009/7

N2 - Cannabinoid receptor 1 (CB1) gene (CNR1) knockout mice are prone to develop anhedonic and helpless behavior after chronic mild stress. In humans, the CB1 antagonist rimonabant increases the risk of depressed mood disorders and anxiety. These studies suggest the hypothesis that genetic variation in CB1 receptor function influences the risk of depression in humans in response to stressful life events. In a population sample (n = 1269), we obtained questionnaire measures of personality (Big Five Inventory), depression and anxiety (Brief Symptom Inventory), and life events. The CNR1 gene was covered by 10 SNPs located throughout the gene to determine haplotypic association. Variations in the CNR1 gene were significantly associated with a high neuroticism and low agreeableness phenotype (explained variance 1.5 and 2.5%, respectively). Epistasis analysis of the SNPs showed that the previously reported functional 5′ end of the CNR1 gene significantly interacts with the 3′ end in these phenotypes. Furthermore, current depression scores significantly associated with CNR1 haplotypes but this effect diminished after covariation for recent life events, suggesting a gene × environment interaction. Indeed, rs7766029 showed highly significant interaction between recent negative life events and depression scores. The results represent the first evidence in humans that the CNR1 gene is a risk factor for depression - and probably also for co-morbid psychiatric conditions such as substance use disorders - through a high neuroticism and low agreeableness phenotype. This study also suggests that the CNR1 gene influences vulnerability to recent psychosocial adversity to produce current symptoms of depression.

AB - Cannabinoid receptor 1 (CB1) gene (CNR1) knockout mice are prone to develop anhedonic and helpless behavior after chronic mild stress. In humans, the CB1 antagonist rimonabant increases the risk of depressed mood disorders and anxiety. These studies suggest the hypothesis that genetic variation in CB1 receptor function influences the risk of depression in humans in response to stressful life events. In a population sample (n = 1269), we obtained questionnaire measures of personality (Big Five Inventory), depression and anxiety (Brief Symptom Inventory), and life events. The CNR1 gene was covered by 10 SNPs located throughout the gene to determine haplotypic association. Variations in the CNR1 gene were significantly associated with a high neuroticism and low agreeableness phenotype (explained variance 1.5 and 2.5%, respectively). Epistasis analysis of the SNPs showed that the previously reported functional 5′ end of the CNR1 gene significantly interacts with the 3′ end in these phenotypes. Furthermore, current depression scores significantly associated with CNR1 haplotypes but this effect diminished after covariation for recent life events, suggesting a gene × environment interaction. Indeed, rs7766029 showed highly significant interaction between recent negative life events and depression scores. The results represent the first evidence in humans that the CNR1 gene is a risk factor for depression - and probably also for co-morbid psychiatric conditions such as substance use disorders - through a high neuroticism and low agreeableness phenotype. This study also suggests that the CNR1 gene influences vulnerability to recent psychosocial adversity to produce current symptoms of depression.

KW - CNR1

KW - Depression

KW - Epistasis

KW - Gene × environment interaction

KW - Haplotype

KW - Personality

UR - http://www.scopus.com/inward/record.url?scp=67449147111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67449147111&partnerID=8YFLogxK

U2 - 10.1038/npp.2009.19

DO - 10.1038/npp.2009.19

M3 - Article

VL - 34

SP - 2019

EP - 2027

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 8

ER -