The additive effect of neurotransmitter genes in pathological gambling

Abstract

As access to gambling increases there is a corresponding increase in the frequency of addiction to gambling, known as pathological gambling. Studies have shown that a number of different neurotransmitters are affected in pathological gamblers and that genetic factors play a role. Polymorphisms at 31 different genes involved in dopamine, serotonin, norepinephrine, GABA and neurotransmitters were genotyped in 139 pathological gamblers and 139 age, race, and sex-matched controls. Multivariate regression analysis was used with the presence or absence of pathological gambling as the dependent variable, and the 31 coded genes as the independent variables. Fifteen genes were included in the regression equation. The most significant were the DRD2, DRD4, DAT1, TPH, ADRA2C, NMDA1, and PS1 genes. The r(2) or fraction of the variance was less than 0.02 for most genes. Dopamine, serotonin, and norepinephrine genes contributed approximately equally to the risk for pathological gambling. These results indicate that genes influencing a range of brain functions play an additive role as risk factors for pathological gambling. Multi-gene profiles in specific individuals may be of assistance in choosing the appropriate treatment.

D4 receptor deficiency in mice has limited effects on impulsivity and novelty seeking

“…These data suggest that the absence of D 4 Rs is not sufficient to cause psychopathologies associated with heightened impulsivity and novelty seeking. Keywords impulsivity; D 4 receptors; mice; delay discounting; Go/No-go; inhibition; novelty seeking; locomotion Psychopathologies including pathological gambling (Comings et al, 2001), substance abuse (Vandenbergh et al, 2000), opiate dependence (Kotler et al, 1997), and attention-deficit hyperactivity disorder (ADHD; Faraone et al, 2001;Grady et al, 2003) are associated with the presence of dopamine D 4 receptor (D 4 R) gene (DRD4) polymorphisms. Novelty-seeking is often associated with these psychopathologies and is also observed in individuals possessing DRD4 alleles containing 7 repeats of a 48-nucleotide sequence (DRD4.7) (Benjamin et al, 1996;Ebstein et al, 1996Ebstein et al, , 1997.…”

The Genetics of Problem and Pathological Gambling: A Systematic Review

“…Among the genes involved in serotonin metabolism, tryptophan hydroxylase (TPH) and tryptophan-2,3-dioxygenase (TDO2) were significantly associated with pathological gambling in the study of Comings et al [11]. MAO-A has also been found to be associated with pathological gambling [33,34] while MAO-B did not show any connection.…”

“…Five twin studies were based on the Vietnam Era Twin Registry (VETR) data, while an additional three datasets were used in three other published studies. Among the studies examining specific genetic factors, five studies published by a Spanish research group analyzed the same dataset, while the four studies published by Comings and his colleagues [10][11][12][13] also used various subsamples of one original dataset. Two Brazilian studies also used an identical dataset of 140 participants [14,15].…”

“…Results of six studies [10,11,13,14,27,28] show a significant association between the dopamine D2 receptor gene (DRD2) and pathological gambling. According to these results, the TaqIA polymorphism of the ANKK1 gene (previously believed to be located within the neighboring DRD2 gene [30]) might have an important role in this association.…”

“…Homozygote DdeI and 800T/C alleles of DRD1 also seem to be associated with pathological gambling [10,14] and comorbid alcohol dependence [29]. Three studies show that long alleles (5 to 8 repeat) of the DRD4 gene are associated with pathological gambling [11,12,31].…”