Association of COMT and SLC6A3 polymorphisms with impulsivity, response inhibition and brain function

Kasparbauer, Anna-Maria; Merten, Natascha; Aichert, Désirée S.; Wöstmann, Nicola; Meindl, Thomas; Rujescu, Dan; Ettinger, Ulrich

doi:10.1016/j.cortex.2015.07.002

Cited by 12 publications

(8 citation statements)

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“…It is understood that such a weighting has to be qualified by investigation of possible functional interactions of both polymorphisms. However, neither the present study nor previous studies have provided support for significant interactions (Caldú et al, 2007; Kasparbauer et al, 2015). To summarize, specific and localized functional effects of dopamine call attention to the fact that it is certainly not feasible to define a global role of dopamine for oculomotor control.…”

Section: Discussioncontrasting

confidence: 99%

“…Moreover, it is also possible that oculomotor parameters after all are not sensitive enough to indicate rather small functional effects of some genetic polymorphisms. In several studies, for instance, genotype effects were not observable in behavioral measures, such as in the antisaccade task or stop-signal tasks, but clearly in brain function measured by BOLD activity (Ettinger et al, 2008; Congdon et al, 2009; Kasparbauer et al, 2015). Keeping these possibilities in mind, we conclude that our data do not provide any evidence of an association between the SCL6A3 3′-UTR-VNTR polymorphism and oculomotor control.…”

Section: Discussionmentioning

confidence: 99%

“…Some findings point to functional associations with antisaccade performance (Ettinger et al, 2008; Haraldsson et al, 2010; Kasparbauer et al, 2015), but differences foremost showed up in BOLD responses. Smooth pursuit seems ideal for studying different mechanisms involved in oculomotor control, because it relies on a sophisticated interplay between motion perception, sensorimotor transformation, and anticipatory abilities (Lisberger, 2010; Kowler et al, 2014).…”

Section: Introductionmentioning

confidence: 98%

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The Role of Dopamine in Anticipatory Pursuit Eye Movements: Insights from Genetic Polymorphisms in Healthy Adults

Billino

Hennig

Gegenfurtner

2016

eNeuro

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There is a long history of eye movement research in patients with psychiatric diseases for which dysfunctions of neurotransmission are considered to be the major pathologic mechanism. However, neuromodulation of oculomotor control is still hardly understood. We aimed to investigate in particular the impact of dopamine on smooth pursuit eye movements. Systematic variability in dopaminergic transmission due to genetic polymorphisms in healthy subjects offers a noninvasive opportunity to determine functional associations. We measured smooth pursuit in 110 healthy subjects genotyped for two well-documented polymorphisms, the COMT Val158Met polymorphism and the SLC6A3 3′-UTR-VNTR polymorphism. Pursuit paradigms were chosen to particularly assess the ability of the pursuit system to initiate tracking when target motion onset is blanked, reflecting the impact of extraretinal signals. In contrast, when following a fully visible target sensory, retinal signals are available. Our results highlight the crucial functional role of dopamine for anticipatory, but not for sensory-driven, pursuit processes. We found the COMT Val158Met polymorphism specifically associated with anticipatory pursuit parameters, emphasizing the dominant impact of prefrontal dopamine activity on complex oculomotor control. In contrast, modulation of striatal dopamine activity by the SLC6A3 3′-UTR-VNTR polymorphism had no significant functional effect. Though often neglected so far, individual differences in healthy subjects provide a promising approach to uncovering functional mechanisms and can be used as a bridge to understanding deficits in patients.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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The Role of Dopamine in Anticipatory Pursuit Eye Movements: Insights from Genetic Polymorphisms in Healthy Adults

Billino

Hennig

Gegenfurtner

2016

eNeuro

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“…The enzymatic activity of COMT is influenced by a common polymorphism, the COMT Val(108/158)Met substitution, which affects the thermostability of COMT and results in an approximate 40% decrease in enzymatic activity and therefore higher levels of dopamine in Met/Met homozygous individuals (Chen et al, 2004). However, results are inconclusive, and further studies are needed (Congdon, Constable, Lesch, & Canli, 2009;Forbes et al, 2009;Gurvich & Rossell, 2014;Kasparbauer et al, 2015;Malloy-Diniz et al, 2013). However, results are inconclusive, and further studies are needed (Congdon, Constable, Lesch, & Canli, 2009;Forbes et al, 2009;Gurvich & Rossell, 2014;Kasparbauer et al, 2015;Malloy-Diniz et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

A Putative Association of COMT Val(108/158)Met with Impulsivity in Binge Eating Disorder

Leehr¹,

Schag²,

Brückmann

et al. 2015

Euro Eating Disorders Rev

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COMT Met/Met homozygous individuals with BED might represent a specific group in the BED spectrum, which shows a higher behavioural impulsivity. The association between COMT Val(108/158)Met with inhibitory control should be interpreted with caution because of the small sample size. Larger replication studies are needed to further elucidate the role of the COMT Val(108/158)Met polymorphism in the regulation of disordered eating behaviour.

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“…66 It was also associated with the executive function of inhibition, which is impaired in adults with ADHD from the general population. 67 Evidence from animal models demonstrates that the dopaminergic function is essentially different in males and females. In rats, estrogen and progesterone modulate dopamine activity in the striatum and nucleus accumbens.…”

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confidence: 99%

COMT and DAT1 genes are associated with hyperactivity and inattention traits in the 1993 Pelotas Birth Cohort: evidence of sex-specific combined effect

Akutagava-Martins

Salatino-Oliveira

Kieling

et al. 2016

jpn

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IntroductionSymptoms of hyperactivity/impulsivity and inattention are dimensionally distributed in the population. Evidence supporting this idea comes from the study of twin pairs from the general population, which demonstrate high heritability estimates for these behavioural traits, ranging from 0.60 to 0.91. [1][2][3] The low end of the distribution would be represented by few behavioural problems and better cognitive function than the high and symptomatic end. This extreme and impairing end would probably be represented by the categorical diagnosis of attention-deficit/hyperactivity disorder (ADHD).4 A study on inhibition, an executive function whose impairments are part of the cognitive deficits seen in individuals with ADHD, demonstrated that performance on inhibition-related tasks were positively associated with ADHD-like traits in a large sample of healthy adults who did not have a first-degree relative with ADHD. 5The heritability estimates for ADHD are essentially the same for both continuous and categorical approaches, consistent with a dimensional view of ADHD and a strong genetic component. [1][2][3]6 Based on the normal distribution of ADHD traits in the general population, the identification and understanding of ADHD susceptibility genes may bene fit from studies of this dimensional characteristic of ADHD in nonclinical samples.2 Despite high heritability estimates, the identification of ADHD genetic susceptibility markers has been difficult, with few replicable findings described so far. 7,8 The main candidates for ADHD molecular genetic studies have been genes involved in the dopamine pathway, given considerable evidence supporting the dopaminergic hypothesis. According to this theory, an Background: Attention-deficit/hyperactivity disorder (ADHD) symptoms are dimensionally distributed in the population. This study aimed to assess the role of the catechol-O-methyltransferase (COMT) and of the dopamine transporter (DAT1) genes on ADHD symptoms in the general population. Methods: We investigated 4101 individuals from the 1993 Pelotas Birth Cohort Study using the parent version of the Strengths and Difficulties Questionnaire (SDQ) at ages 11 and 15 years. The SDQ hyperactivity/inattention scores were the main outcomes. Results: Linear regression analyses demonstrated that the increasing number of COMT 158 Val and DAT1 10R alleles significantly predicted increasing SDQ hyperactivity/inattention scores in boys at both 11 and 15 years of age (β coefficient = 0.049, t = 2.189, p = 0.029, R 2 = 0.012, and β coefficient = 0.064, t = 2.832, p = 0.005, R 2 = 0.008, respectively). The presence of both COMT 158 Val and DAT1 10R alleles was also associated with full categorical ADHD diagnosis at 18 years of age in boys (χ 2 = 4.561, p = 0.033, odds ratio 2.473, 95% confidence interval 1.048-5.838) from this cohort. We did not observe these associations in girls. Limitations: Our analyses of SDQ hyperactivity/inattention scores were not corrected for SDQ scores of conduct problems because these variables were h...

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Association of COMT and SLC6A3 polymorphisms with impulsivity, response inhibition and brain function

Cited by 12 publications

References 83 publications

The Role of Dopamine in Anticipatory Pursuit Eye Movements: Insights from Genetic Polymorphisms in Healthy Adults

The Role of Dopamine in Anticipatory Pursuit Eye Movements: Insights from Genetic Polymorphisms in Healthy Adults

A Putative Association of COMT Val(108/158)Met with Impulsivity in Binge Eating Disorder

COMT and DAT1 genes are associated with hyperactivity and inattention traits in the 1993 Pelotas Birth Cohort: evidence of sex-specific combined effect

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