The International Journal of Neuropsychopharmacology

Research Article

Association study of a functional catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and suicide attempts in patients with alcohol dependence

Gordana Nedica1, Matea Nikolaca1, Korona Nenadic Sviglina2, Dorotea Muck-Selera1, Fran Boroveckia3 and Nela Pivaca1 c1

a1 Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia

a2 Center for Alcoholism and other Addictions, Psychiatric Hospital Vrapce, Zagreb, Croatia

a3 Department of Neurology, University Hospital Center Zagreb, Zagreb, Croatia, and Department for Functional Genomics, Center for Translational and Clinical Research, University of Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, Croatia

Abstract

Alcohol dependence is frequently associated with aggressive and suicidal behaviour. Genetic factors contribute to both behaviours. Candidate genes, related to suicide and aggression, include genes involved in serotonin, norepinephrine and dopamine pathways. The enzyme catechol-O-methyl transferase (COMT) degrades dopamine, epinephrine and norepinephrine. The functional polymorphism (COMT Val108/158Met) affects COMT activity, with the valine (Val) variant associated with higher and the methionine (Met) variant with lower COMT activity. This polymorphism is associated with aggressive and suicidal behaviour, but the literature data on this relationship is contradictory and inconsistent. The hypothesis of this study was that Met allele carriers with alcohol dependence will have a higher frequency of suicide attempts compared to other genotypes. Participants were 312 male and 81 female medication-free patients with alcohol dependence and 487 male and 122 female unrelated, non-suicidal medication-free Caucasian healthy subjects. Our results showed significant (χ2 test with standardized residuals) differences in the frequencies of COMT variants in all alcoholics, alcoholics with different comorbid diagnoses, and in male but not in female alcoholics, with or without suicide attempts. Male alcoholic suicide attempters, compared to male non-attempters, had the higher frequency of Met/Met genotype or Met allele, and significantly (Kruskal–Wallis ANOVA on ranks and Mann–Whitney test) higher aggression and depression scores. These results confirmed the associations between Met allele and aggressive behaviour or violent suicide attempts in various psychiatric diagnoses, and suggested that Met allele of the COMT Val108/158 Met might be used as an independent biomarker of suicidal behaviour across different psychopathologies.

(Received March 10 2010)

(Reviewed May 30 2010)

(Revised June 07 2010)

(Accepted August 07 2010)

(Online publication September 22 2010)

Correspondence:

c1 Address for correspondence: Dr N. Pivac, Division of Molecular Medicine, Rudjer Boskovic Institute, P. O. Box 180, HR-10002 Zagreb, Croatia. Tel.: 385 1 4571 207 Fax: 385 1 456 1010 Email: npivac@irb.hr

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