Aggressive behavior, related conduct problems, and variation in genes affecting dopamine turnover.
A number of dopamine-related genes have been implicated in the etiology of violent behavior and conduct problems. Of these genes, the ones that code for the enzymes that influence the turnover of dopamine (DA) have received the most attention. In this study, we investigated 12 genetic polymorphisms in four genes involved with DA functioning (COMT, MAOA and MAOB, and DbetaH) in 179 incarcerated male Russian adolescents and two groups of matched controls: boys without criminal records referred to by their teachers as (a) "troubled-behavior-free" boys, n=182; and (b) "troubled-behavior" boys, n=60. The participants were classified as (1) being incarcerated or not, (2) having the DSM-IV diagnosis of conduct disorder (CD) or not, and (3) having committed violent or nonviolent crimes (for the incarcerated individuals only). The findings indicate that, although no single genetic variant in any of the four genes differentiated individuals in the investigated groups, various linear combinations (i.e., haplotypes) and nonlinear combinations (i.e., interactions between variants within and across genes) of genetic variants resulted in informative and robust classifications for two of the three groupings. These combinations of genetic variants differentiated individuals in incarceration vs. nonincarcerated and CD vs. no-CD groups; no informative combinations were established consistently for the grouping by crime within the incarcerated individuals. This study underscores the importance of considering multiple rather than single markers within candidate genes and their additive and interactive combinations, both with themselves and with nongenetic indicators, while attempting to understand the genetic background of such complex behaviors as serious conduct problems.
Grigorenko
Elena L
EL
Yale University Child Study Center, New Haven, Connecticut 06519, USA. elena.grigorenko@yale.edu
De Young
Colin G
CG
Eastman
Maria
M
Getchell
Marya
M
Haeffel
Gerald J
GJ
Klinteberg
Britt af
Ba
Koposov
Roman A
RA
Oreland
Lars
L
Pakstis
Andrew J
AJ
Ponomarev
Oleg A
OA
Ruchkin
Vladislav V
VV
Singh
Jay P
JP
Yrigollen
Carolyn M
CM
D000293:Adolescent; D000374:Aggression / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics; D019955:Conduct Disorder / Q000235:genetics* / Q000523:psychology; D003415:Crime; D004298:Dopamine / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D014754:Violence / Q000523:psychology
D005819:Genetic Markers; D004299:Dopamine beta-Hydroxylase; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004298:Dopamine