COMT genotype, gambling activity, and cognition

Abstract

Neuropsychological studies of adults with problem gambling indicate impairments across multiple cognitive domains. Catechol-O-methyltransferase (COMT) plays a unique role in the regulation of dopamine in the prefrontal cortex, and has been implicated in the cognitive dysfunction evident in problem gambling. This study examined adults with varying levels of gambling behavior to determine whether COMT genotype was associated with differences in gambling symptoms and cognitive functioning. 260 non-treatment-seeking adults aged 18-29 years with varying degrees of gambling behavior provided saliva samples for genotyping COMT val158met (rs4680). All subjects underwent clinical evaluations and neurocognitive assessment of decision-making, working memory, and impulsivity. The Val/Val COMT genotype was associated with the largest percentage of subjects with gambling disorder (31.8%), a rate significantly different from the Val/Met (13.2%) group (p = 0.001). The Val/Val COMT group was also associated with significantly more gambling disorder diagnostic criteria being met, greater frequency of gambling behavior, and significantly worse cognitive performance on the Cambridge Gamble Task (risk adjustment and delay aversion) and the Spatial Working Memory task (total errors). This study adds to the growing literature on the role of COMT in impulsive behaviors by showing that the Val/Val genotype was associated with specific clinical and cognitive elements among young adults who gamble, in the absence of differences on demographic measures and other cognitive domains. Future work should consider using genotyping to explore whether certain polymorphisms predict subsequent development of impulsive behaviors including gambling disorder, and treatment outcomes.

Temperament and Character Inventory in Bipolar Disorder versus Healthy Controls and Modulatory Effects of 3 Key Functional Gene Variants

“…Moreover, also in the HC group, this association was limited to male subjects, suggesting a gene x sex effect in the determination of NS levels. More in detail, we found that the Val/Val genotype was associated with higher NS levels in this subgroup of subjects, partially consistent with literature data about the effects of this genotype on impulsivity and addictive behaviors [64, 65], which are both associated with NS dimensions [66, 67]. Furthermore, the lack of association observed in BD sample may support the hypothesis that BD pathophysiological process alters the neurobiological substrates of NS, as previously stated.…”

Gambling disorder: an integrative review of animal and human studies

“…In gene‐association studies, polymorphisms in a number of genes, including MAOA, SLC6A4 (5‐HTTLPR), DRD3, DRD4, HTR2A , and COMT , have been linked to GD . One interesting translational report linked DRD3 to GD in humans as well as in a rodent model .…”

“…211 In gene-association studies, polymorphisms in a number of genes, including MAOA, SLC6A4 (5-HTTLPR), DRD3, DRD4, HTR2A, and COMT, have been linked to GD. 20,145,[212][213][214][215] One interesting translational report linked DRD3 to GD in humans as well as in a rodent model. 145 First, addictionrelated SNPs were genotyped in GD patients, which revealed that DRD3 and CAMK2D were significantly associated with GD compared with controls.…”

A case-control association study of COMT rs4680 Polymorphism with Obsessive-Compulsive Disorder and Cognitive Functions: The role of sex

“…The results of assessments of demographic variables showed that the OCD and control groups did not differ signi cantly in terms of mean age (p = 0.27, t = 1.09), sex distribution (p = 0.2, chi squared = 57. 17) or handedness (p = 0.32, chi squared = 0.97). There were also no signi cant differences in education level (p = 0.31, chi squared = 87.5) or ethnicity (p = 0.09, chi squared = 6.34).…”

“…Animal and human studies have also pointed out dysregulations in a brain network, including the hippocampal formation (HF) and the ventrolateral prefrontal cortex (VLPFC) (15), which initiates processes that support declarative memory components such as episodic and semantic encoding and retrieval (16). Dopamine, as one of the main neurotransmitters, regulates memory functions such as episodic memory and long-term potentiation in these regions (17,18). Therefore, genes regulating the dopaminergic system appear to be suitable candidates for association with cognitive functions such as memory (19).…”