A G Segura1, M Mitjans1, E Jiménez2, M Fatjó-Vilas3, V Ruiz4, P A Saiz5, M P García-Portilla5, L González-Blanco5, J Bobes5, E Vieta2, A Benabarre2, B Arias6. 1. Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, IBUB, University of Barcelona, CIBERSAM, Barcelona, Spain. 2. Bipolar Disorder Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. 3. Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, IBUB, University of Barcelona, CIBERSAM, Barcelona, Spain; FIDMAG Germanes Hospitalaries Research Foundation, CIBERSAM, Barcelona, Spain. 4. Institut Clínic de Neurociencies, Hospital Clínic, Barcelona, Spain. 5. Department of Psychiatry, School of Medicine, University of Oviedo, CIBERSAM, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto de Neurociencias del Principado de Asturias (INEUROPA), Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain. 6. Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, IBUB, University of Barcelona, CIBERSAM, Barcelona, Spain. Electronic address: barbara.arias@ub.edu.
Abstract
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.
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 BDpatients 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-BPrs7728378-C carriers (p = 0.004; OR = 3.05), FKBP5rs3777747-AA (p = 0.039; OR = 0.34) and FKBP5rs2766533-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 BDpatients. 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.