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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.

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Acknowledgements

This work was supported in part by the Union Europea Fondo Social Europeo (FEDER), Instituto de Salud Carlos III-FIS (PI10/02758) and Gobierno de Extremadura Consejería de Empleo, Empresa e Innovación, FSE (IB13186 and PD10199), CHU Montpellier (PHRC UF 7653), Agence Nationale de la Recherche (ANR NEURO 2007 ‘GENESIS’).

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Correspondence to E Peñas-Lledó.

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Dr Blasco-Fontecilla has received lecture fees from Eli Lilly, AB-Biotics and Shire. The remaining authors declare no conflict of interest.

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Peñas-Lledó, E., Guillaume, S., Naranjo, M. et al. A combined high CYP2D6-CYP2C19 metabolic capacity is associated with the severity of suicide attempt as measured by objective circumstances. Pharmacogenomics J 15, 172–176 (2015). https://doi.org/10.1038/tpj.2014.42

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