High rates of suicide among adolescents are a growing concern worldwide, while 8% of adolescents show high suicidal risk in Croatia. There are different psychiatric, psychological, environmental, biological and genetic factors for suicidal behavior that can lead to completed suicide. Aggression and agitation present risk factors for suicide. Gene for the enzyme catechol-o-methyl-transferase (COMT), that degrades dopamine, is frequently studied candidate gene for suicide risk. A functional polymorphism COMT Val108/158Met, consists of G to A transition, i.e. substitution of valine (Val) with methionine (Met). The Val/Val genotype has a 3-4 times higher COMT activity than the Met/Met genotype. This polymorphism was associated with suicidal behavior in adults. The hypothesis of this study was that COMT Val108/158Met polymorphism will be significantly associated with suicidal behavior and/or aggression in adolescents. The study included 187 female and 141 male adolescents (15.2 ± 2.4 years, range 7-19). The psychiatric diagnoses, suicidal behavior and aggression were established according to the SCID and DSM- IV criteria, and the Overt Aggression Symptom Checklist. DNA was isolated from the blood samples taken during regular laboratory check- ups. Genotyping was carried out on the ABI Prism 7000 Sequencing Detection System apparatus (ABI, Foster City, USA) with Taqman- based allele-specific PCR, according to the procedure described by Applied Biosystems (ABI, Foster City, USA). Statistical evaluation of the data was done using the Chi-square test, with p <0.05. All adolescents were subdivided into control subjects (without psychiatric diagnoses and without suicidal behavior), and suicidal and non-suicidal adolescents (with psychiatric diagnoses). COMT Val108/158Met genotypes were in the Hardy-Weinberg equilibrium, and no deviation was found in control (χ2 =0.490, p =0.484), suicidal (χ2 =0.070, p =0.703) or non-suicidal (χ2 =0.700, p = 0.402) groups. Control subjects and suicidal and non-suicidal adolescents had similar distribution of the Val/Val, Val/Met and Met/Met genotypes (χ2 = 5.629, df =4, p = 0.229), or Val and Met alleles (χ2 =4.376, df =2, p =0.0112). There were no significant differences in the distribution of the COMT Val108/158Met genotypes between adolescents with or without: verbal aggression (χ2 =2.867, df =2, p =0.238), physical aggression against self (χ2 =1.025, df =2, p =0.599), physical aggression against objects (χ2 =3.313, df =2, p =0.191), or physical aggression against other people (χ2 =0.225, df =2, p =0.893). The distribution of the COMT alleles did not differ significantly between adolescents with or without: verbal aggression (χ2 =2.856 , df =1, p =0.091), physical aggression against self (χ2 =0.166 , df =1, p =0.634), physical aggression against objects (χ2 =2.329, df =1, p =0.127), or physical aggression against other people (χ2 =0.081, df =1, p =0.776). Our preliminary results, showing similar distribution of the COMT Val108/158Met variants between suicidal and non-suicidal adolescents, or between non- aggressive and aggressive adolescents, did not confirm our hypothesis that suicidal behavior, and/or aggression, is significantly associated with the COMT Val108/158Met polymorphism in adolescents. The present findings suggest that further studies with larger samples should be included to evaluate the role of COMT Val108/158Met polymorphism in suicidal or aggressive behavior.
Read full abstract