title: A combined high CYP2D6-CYP2C19 metabolic capacity is associated with the severity of suicide attempt as measured by objective circumstances.
abstract: This study examined, for the first time, whether a high CYP2D6-CYP2C19 metabolic capacity combination increases the likelihood of suicidal intent severity in a large study cohort. Survivors of a suicide attempt (n=587; 86.8% women) were genotyped for CYP2C19 (*2, *17) and CYP2D6 (*3, *4, *4xN, *5, *6, *10, wtxN) genetic variation and evaluated with the Beck Suicide Intent Scale (SIS). Patients with a high CYP2D6-CYP2C19 metabolic capacity showed an increased risk for a severe suicide attempt (P<0.01) as measured by the SIS-objective circumstance subscale (odds ratio (OR)=1.37; 95% confidence interval (CI)=1.05-1.78; P=0.02) after adjusting for confounders (gender, age, level of studies, marital status, mental disorders, tobacco use, family history of suicide, personal history of attempts and violence of the attempt). Importantly, the risk was greater in those without a family history of suicide (OR=1.82; CI=1.19-2.77; P=0.002). Further research is warranted to evaluate whether the observed relationship is mediated by the role of CYP2D6 and CYP2C19 involvement in the endogenous physiology or drug metabolism or both.
authors.affiliation: CICAB Clinical Research Center, Extremadura University Hospital & Medical School, Badajoz, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Peñas-Lledó
authors.affiliation: 1] CHU Montpellier, Hôpital Lapeyronie, Psychiatric Emergency and Post Emergency Department, Pole Urgence, Montpellier, France [2] Inserm, U1061 Montpellier, France [3] Université Montpellier I, Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Guillaume
authors.affiliation: CICAB Clinical Research Center, Extremadura University Hospital & Medical School, Badajoz, Spain.
authors.forename: M E G
authors.initials: ME
authors.lastname: Naranjo
authors.affiliation: CICAB Clinical Research Center, Extremadura University Hospital & Medical School, Badajoz, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Delgado
authors.affiliation: 1] Inserm, U1061 Montpellier, France [2] Université Montpellier I, Montpellier, France.
authors.forename: I
authors.initials: I
authors.lastname: Jaussent
authors.affiliation: 1] Department of Psychiatry, IDIPHIM-Puerta de Hierro Hospital, Madrid, Spain [2] CIBERSAM, Instituto de Salud Carlos III, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Blasco-Fontecilla
authors.affiliation: 1] CHU Montpellier, Hôpital Lapeyronie, Psychiatric Emergency and Post Emergency Department, Pole Urgence, Montpellier, France [2] Inserm, U1061 Montpellier, France [3] Université Montpellier I, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Courtet
authors.affiliation: 1] CICAB Clinical Research Center, Extremadura University Hospital & Medical School, Badajoz, Spain [2] CIBERSAM, Instituto de Salud Carlos III, Spain.
authors.forename: A
authors.initials: A
authors.lastname: LLerena
mesh_terms: D000328:Adult; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism*; D012306:Risk; D013405:Suicide / Q000523:psychology; D013406:Suicide, Attempted / Q000523:psychology
chemical_list: C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6
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