Association of childhood trauma and genetic variability of CRH-BP and FKBP5 genes with suicidal behavior in bipolar patients.
Adult
Bipolar Disorder
/ genetics
Carrier Proteins
/ genetics
Child
Child Abuse
/ psychology
Cross-Sectional Studies
Female
Gene-Environment Interaction
Genotype
Humans
Hypothalamo-Hypophyseal System
Male
Middle Aged
Pituitary-Adrenal System
Polymorphism, Single Nucleotide
Risk Factors
Suicidal Ideation
Suicide
Tacrolimus Binding Proteins
/ genetics
Bipolar disorder
CRH-BP
Childhood trauma
FKBP5
HPA axis
Suicidal behavior
Journal
Journal of affective disorders
ISSN: 1573-2517
Titre abrégé: J Affect Disord
Pays: Netherlands
ID NLM: 7906073
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
received:
25
02
2019
revised:
03
05
2019
accepted:
07
05
2019
pubmed:
14
6
2019
medline:
12
5
2020
entrez:
14
6
2019
Statut:
ppublish
Résumé
Around 8% of bipolar disorder (BD) patients die by suicide every year, accounting for the highest rate among the psychiatric population. Suicidal behavior (SB) is mediated by an intertwining system of extrinsic and intrinsic factors. Childhood trauma (CT) and gene variants of the stress-management hypothalamic-pituitary-adrenal (HPA) axis have been reported as risk factors for SB. The aim of this study was to elucidate the association of CT and HPA axis genetic variants with SB. 135 BD patients were recruited for clinical assessment of CT and SB by means of the Childhood Trauma Questionnaire (CTQ) and the Columbia Suicide Severity Rating Scale (C-SSRS), respectively. A total of 28 single nucleotide polymorphisms (SNPs) from 8 HPA axis genes (POMC, NR3C2, CRH-BP, NR3C1, FKBP5, CRHR2, CRHR1, and MC2R) were genotyped. The analyses showed an association of total CTQ score (p = 0.003), emotional abuse (p = 0.001), sexual abuse (p = 0.005) and emotional neglect (p = 0.005) with SB. CRH-BP rs7728378-C carriers (p = 0.004; OR = 3.05), FKBP5 rs3777747-AA (p = 0.039; OR = 0.34) and FKBP5 rs2766533-GG genotypes (p = 0.001; OR = 2.93) were associated with SB although only rs2766533 survived multiple test correction. No gene-environment interaction was found. The relatively small sample size limits the statistical power to detect smaller environmental and genetic effects. Cross-sectional data collection in psychometric assessments can yield biased data. The present study characterizes novel SB risk factors and replicates previous findings in BD patients. CT and variability in CRH-BP and FKBP5 genes should be further studied for a better understanding of SB and ultimately help in suicide prevention.
Sections du résumé
BACKGROUND
Around 8% of bipolar disorder (BD) patients die by suicide every year, accounting for the highest rate among the psychiatric population. Suicidal behavior (SB) is mediated by an intertwining system of extrinsic and intrinsic factors. Childhood trauma (CT) and gene variants of the stress-management hypothalamic-pituitary-adrenal (HPA) axis have been reported as risk factors for SB. The aim of this study was to elucidate the association of CT and HPA axis genetic variants with SB.
METHODS
135 BD patients were recruited for clinical assessment of CT and SB by means of the Childhood Trauma Questionnaire (CTQ) and the Columbia Suicide Severity Rating Scale (C-SSRS), respectively. A total of 28 single nucleotide polymorphisms (SNPs) from 8 HPA axis genes (POMC, NR3C2, CRH-BP, NR3C1, FKBP5, CRHR2, CRHR1, and MC2R) were genotyped.
RESULTS
The analyses showed an association of total CTQ score (p = 0.003), emotional abuse (p = 0.001), sexual abuse (p = 0.005) and emotional neglect (p = 0.005) with SB. CRH-BP rs7728378-C carriers (p = 0.004; OR = 3.05), FKBP5 rs3777747-AA (p = 0.039; OR = 0.34) and FKBP5 rs2766533-GG genotypes (p = 0.001; OR = 2.93) were associated with SB although only rs2766533 survived multiple test correction. No gene-environment interaction was found.
LIMITATIONS
The relatively small sample size limits the statistical power to detect smaller environmental and genetic effects. Cross-sectional data collection in psychometric assessments can yield biased data.
CONCLUSIONS
The present study characterizes novel SB risk factors and replicates previous findings in BD patients. CT and variability in CRH-BP and FKBP5 genes should be further studied for a better understanding of SB and ultimately help in suicide prevention.
Identifiants
pubmed: 31195252
pii: S0165-0327(19)30372-6
doi: 10.1016/j.jad.2019.05.014
pii:
doi:
Substances chimiques
Carrier Proteins
0
corticotropin releasing factor-binding protein
134773-81-2
Tacrolimus Binding Proteins
EC 5.2.1.-
tacrolimus binding protein 5
EC 5.2.1.8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15-22Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.