Association Between Polymorphisms of the Dopamine Receptor D2 and Catechol-o-Methyl Transferase Genes and Cognitive Function

Bolton, Jennifer L.; Marioni, Riccardo E.; Deary, Ian J.; Harris, Sarah E.; Stewart, Marlene; Murray, Gordon D.; Fowkes, F. G. R.; Price, Jackie F.

doi:10.1007/s10519-010-9372-y

Cited by 37 publications

(34 citation statements)

References 55 publications

(61 reference statements)

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“…This issue is of theoretical significance because other indices, such as fluid intelligence, have also been associated with intraindividual variability (Li et al, 2004Rabbitt, Osman, Moore, & Stollery, 2001;Ram et al, 2005) and dopamine neuromodulation (e.g., Bäckman et al, 2000;Bolton et al, 2010;Volkow et al, 1998). Direct comparisons of the associations of variability measures and other indices of cognitive performance to dopamine neuromodulation are needed to shed light on this issue.The present study makes two novel contributions to the existing literature on performance variability.…”

Section: Discussionmentioning

confidence: 99%

Higher intraindividual variability is associated with more forgetting and dedifferentiated memory functions in old age

et al. 2011

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a b s t r a c tIntraindividual trial-to-trial reaction time (RT) variability is commonly found to be higher in clinical populations or life periods that are associated with impaired cognition. In the present study, higher within-person trial-to-trial RT variability in a perceptual speed task is related to more forgetting and dedifferentiation of memory functions in older adults (aged 60-71 years). More specifically, our study showed that individuals in a high-variability group (n = 175) forgot more memory scenes over a 1-week retention interval than individuals in the low-variability group (n = 174). In contrast, slower RT speed was associated with poorer episodic memory in general, but unrelated to the amount of forgetting. Moreover, results from multiple group latent factor analyses showed that episodic memory and working memory functions were more highly correlated in the high-variability (r = .63) than in the low-variability (r = .25) group. Given that deficits in dopamine (DA) modulation may underlie increases in RT variability, the present findings are in line with (i) recent animal studies implicating DA in long-term episodic memory consolidation and (ii) neurocomputational work linking DA modulation of performance variability to dedifferentiation of cognitive functions in old age.

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Section: Discussionmentioning

confidence: 99%

Higher intraindividual variability is associated with more forgetting and dedifferentiated memory functions in old age

et al. 2011

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“…Such cognitive benefits have been found to correlate with lower brain activation, indicating more efficient information processing (Egan et al 2001;Sambataro et al 2009). However, several studies have failed to replicate these findings (Blanchard et al 2011;Bolton et al 2010;Stuart et al 2014), and two meta-analyses only documented a COMT Met superiority on measures of general cognition, such as IQ (Barnett et al 2007(Barnett et al , 2008.…”

Section: Comt Polymorphismmentioning

confidence: 99%

Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging

et al. 2015

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Increasing evidence from cross-sectional and longitudinal molecular-genetic studies suggests that effects of common genetic variations on cognitive functioning increase with aging. We review the influence of candidate genes on brain functioning in old age, focusing on four genetic variations that have been extensively investigated: APOE, BDNF, COMT, and KIBRA. Similar to the behavioral evidence, there are reports from agecomparative studies documenting stronger genetic effects on measures of brain functioning in older adults compared to younger adults. This pattern suggests disproportionate impairments of neural processing among older individuals carrying disadvantageous genotypes. We discuss various factors, including gene-gene interactions, study population characteristics, lifestyle factors, and diseases, that need to be considered in future studies and may help understand inconsistent findings in the extant literature.

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“…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%

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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Association Between Polymorphisms of the Dopamine Receptor D2 and Catechol-o-Methyl Transferase Genes and Cognitive Function

Cited by 37 publications

References 55 publications

Higher intraindividual variability is associated with more forgetting and dedifferentiated memory functions in old age

Higher intraindividual variability is associated with more forgetting and dedifferentiated memory functions in old age

Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging

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

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