DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability

Xu, Huji; Kellendonk, Christoph; Simpson, Eleanor H.; Keilp, John G.; Bruder, Gerard E.; Polan, H. Jonathan; Kandel, Eric R.; Gilliam, T. Conrad

doi:10.1016/j.schres.2006.10.001

Cited by 78 publications

(75 citation statements)

References 20 publications

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“…Finally, CC homozygotes solved fewer problems on first choice in OTS and took on average more choices to achieve the correct answer, compared to CT heterozygotes. In general, these findings are in accord with previous studies that have reported CC homozygotes being compromised when compared to CT and TT carriers in working memory (Xu et al., 2007) and tests of executive function (Rodriguez‐Jimenez et al., 2006). CC genotype has been associated with lowest striatal D2 receptor availability and supposedly higher synaptic dopamine levels in the striatum, compared to other genotypes (Hirvonen et al., 2004, 2005; Hirvonen, Laakso, et al., 2009).…”

Section: Discussionmentioning

confidence: 99%

“…There were several limitations in this study, the first of which being the sample size which prevented further analyses of potential interest such as investigating any interaction between the DRD2 and COMT variants (Xu et al., 2007) and subgroup analysis of the trauma scale, given previous findings of the differential effects of trauma type on cognition (Green et al., 2014). Furthermore, we have no information about the mRNA or protein level expression of genes under investigation in the individuals who took part in this study, nor about other genetic polymorphisms that might affect aspects of the dopaminergic systems such as those encoding dopamine transporter, (Sesack, Hawrylak, Matus, Guido, & Levey, 1998), and monoamine oxidase A ( MAOA ) which was recently shown to interact with early life stress (Zohsel et al., 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The genetic studies looking at the association of DRD2 C957T with cognitive function have generally shown that CC homozygosity is associated with poorer performance on tests of executive function and working memory in the general population (Rodriguez‐Jimenez et al., 2006; Xu et al., 2007), decreased general cognitive ability in elderly healthy males and females (Bolton et al., 2010), impaired executive function and cognitive flexibility in HIV‐infected individuals who abuse alcohol (Villalba, Devieux, Rosenberg, & Cadet, 2015), and poorer performance in an attentional switching task in CC homozygotic females (Gurvich & Rossell, 2015). The T allele and TT homozygosity has been associated with better avoidance learning from negative outcomes in both forced choice and reaction time tasks (Frank, Doll, Oas‐Terpstra, & Moreno, 2009; Frank, Moustafa, Haughey, Curran, & Hutchison, 2007), better striatally mediated reflexive learning (Xie, Maddox, McGeary, & Chandrasekaran, 2015) and rule‐based category learning in healthy young adults (Byrne, Davis, & Worthy, 2016), and with superior performance in an attentional switching task in TT homozygotic males (Gurvich & Rossell, 2015).…”

Section: Introductionmentioning

confidence: 99%

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The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress

et al. 2017

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IntroductionPrevious research has indicated that variation in genes encoding catechol‐O‐methyltransferase (COMT) and dopamine receptor D2 (DRD2) may influence cognitive function and that this may confer vulnerability to the development of mental health disorders such as schizophrenia. However, increasing evidence suggests environmental factors such as early life stress may interact with genetic variants in affecting these cognitive outcomes. This study investigated the effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress in healthy adults.MethodsOne hundred and twenty‐two healthy adult males (mean age 35.2 years, range 21–63) were enrolled in the study. Cognitive function was assessed using Cambridge Neuropsychological Test Automated Battery and early life stress was assessed using the Childhood Traumatic Events Scale (Pennebaker & Susman, 1988).Results DRD2 C957T was significantly associated with executive function, with CC homozygotes having significantly reduced performance in spatial working memory and spatial planning. A significant genotype–trauma interaction was found in Rapid Visual Information Processing test, a measure of sustained attention, with CC carriers who had experienced early life stress exhibiting impaired performance compared to the CC carriers without early life stressful experiences. There were no significant findings for COMT Val158Met.ConclusionsThis study supports previous findings that DRD2 C957T significantly affects performance on executive function related tasks in healthy individuals and shows for the first time that some of these effects may be mediated through the impact of childhood traumatic events. Future work should aim to clarify further the effect of stress on neuronal systems that are known to be vulnerable in mental health disorders and more specifically what the impact of this might be on cognitive function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress

et al. 2017

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“…The inverted U-shaped modulation of COMT or DRD2 genetic variant on behavioral performance (Mattay et al, 2003;Giakoumaki et al, 2008;Fallon et al, 2013) or brain function (Bertolino et al, 2009a;Dang et al, 2012) has been reported separately. Based on the interaction effects between COMT and DRD2 on behavioral performance (Reuter et al, 2006;Xu et al, 2007), we hypothesize that brain functional organization may also show interaction effects between COMT and DRD2.…”

Section: Introductionmentioning

confidence: 99%

Functional Connectivity in Healthy Subjects Is Nonlinearly Modulated by the COMT and DRD2 Polymorphisms in a Functional System-Dependent Manner

Tian¹,

Qin

Liu

et al. 2013

J. Neurosci.

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The dopamine system is known to modulate brain function in an inverted U-shaped manner. Recently, the functional networks of the brain were categorized into two systems, a "control system" and a "processing system." However, it remains unclear whether the inverted U-shaped model of dopaminergic modulation could be applied to both of these functional systems. The catechol-O-methyltransferase (COMT) and dopamine D 2 receptor (DRD2) were genotyped in 258 healthy young human subjects. The local and long-range functional connectivity densities (FCDs) of each voxel were calculated and compared in a voxel-wise manner using a two-way (COMT and DRD2 genotypes) analysis of covariance. The resting-state functional connectivity analysis was performed to determine the functional networks to which brain regions with significant FCD differences belonged. Significant COMT ϫ DRD2 interaction effects were found in the local FCDs of the superior portion of the right temporal pole (sTP) and left lingual gyrus (LG) and in the long-range FCDs of the right putamen and left medial prefrontal cortex (MPFC). Post hoc tests showed nonlinear relationships between the genotypic subgroups and FCD. In the control system, the sTP and putamen, components of the salience network, showed a U-shaped modulation by dopamine signaling. In the processing system, however, the MPFC of the default-mode network and the LG of the visual network showed an inverted U-shaped modulation by the dopamine system. Our findings suggest an interaction between COMT and DRD2 genotypes and show a functional system-dependent modulation of dopamine signaling.

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“…Individuals with the homozygous for the C (cytosine) allele, who have the highest degree of striatal binding potential as a result, demonstrated poorer performance in a word serial position test (Xu et al 2007). Further, as with DAT1, there is an additive effect with COMT on task performance.…”

Section: Dopamine Receptor Genes (Drd)mentioning

confidence: 99%

The Role of Host Genetics in the Susceptibility for HIV-associated Neurocognitive Disorders

2008

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Despite progress in the treatment of the Human Immunodeficiency virus (HIV), there continues to be a high prevalence of infected individuals who develop neurocognitive deficits and disorders. Our understanding of the potential cause of HIV-associated neurocognitive disorders (HAND) continues to develop on many fronts. Among them is the study of host genetics. Here, we review the most current information regarding the association between host genetics and risk for HIV infection, AIDS, and HAND. We focus on the role of dopamine dysfunction in the etiology of HAND, and propose a number of genetic polymorphisms within genes related to dopaminergic functioning and other neurobiological factors that may confer vulnerability or protection against HAND.

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DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability

Cited by 78 publications

References 20 publications

The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress

The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress

Functional Connectivity in Healthy Subjects Is Nonlinearly Modulated by the COMT and DRD2 Polymorphisms in a Functional System-Dependent Manner

The Role of Host Genetics in the Susceptibility for HIV-associated Neurocognitive Disorders

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