Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Frank, Michael J.; Fossella, John

doi:10.1038/npp.2010.96

Cited by 170 publications

(167 citation statements)

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“…Two genes that have been associated with various psychiatric and neurological disorders and which have attracted attention due to their role in cognitive and emotional processes are the genes encoding for the enzyme catechol‐O‐methyltransferase ( COMT ; Dickinson & Elvevåg, 2009; Scheggia, Sannino, Luisa Scattoni, & Papaleo, 2012; Tunbridge, Harrison, & Weinberger, 2006) and the dopamine receptor D2 ( DRD2 ; Frank & Fossella, 2011; Huertas, Bühler, Echeverry‐Alzate, Giménez, & López‐Moreno, 2012; Kellendonk et al., 2006). COMT is responsible for breaking down ~50–60% of dopamine produced in the frontal cortex (Yavich, Forsberg, Karayiorgou, Gogos, & Männistö, 2007).…”

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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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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“…The ability to learn from positive or negative reinforcement can be predicted by variability related to single-nucleotide polymorphisms (SNPs) affecting D1 and D2 gene expression in the go/approach and no-go/avoid pathways (Doll et al, 2011;Frank & Hutchison, 2009;Frank et al, 2007a, b). Specifically, the go/no-go model predicts that reduced striatal D2 density should be associated with impaired accuracy on avoid trials, together with spared accuracy on approach trials in the PST (Frank, D'Lauro, C., & Curran, 2007;Frank & Fossella, 2011;Frank & Hutchison, 2009). Consistent with this prediction, Klein and colleagues (2007) demonstrated that male carriers of the A1 allele (A1/A1 and A2/A1 combined) of the Taq1A SNP of the DRD2 gene, which is associated with reduced D2 expression (Thompson et al, 1997; but see Zhang et al, 2007), were selectively impaired at avoiding the bad stimulus during the test phase.…”

Section: Geneticsmentioning

confidence: 99%

Constraints on decision making: Implications from genetics, personality, and addiction

Baker

Stockwell

Holroyd

2013

Cogn Affect Behav Neurosci

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An influential neurocomputational theory of the biological mechanisms of decision making, the "basal ganglia go/no-go model," holds that individual variability in decision making is determined by differences in the makeup of a striatal system for approach and avoidance learning. The model has been tested empirically with the probabilistic selection task (PST), which determines whether individuals learn better from positive or negative feedback. In accordance with the model, in the present study we examined whether an individual's ability to learn from positive and negative reinforcement can be predicted by genetic factors related to the midbrain dopamine system. We also asked whether psychiatric and personality factors related to substance dependence and dopamine affect PST performance. Although we found characteristics that predicted individual differences in approach versus avoidance learning, these observations were qualified by additional findings that appear inconsistent with the predictions of the go/no-go model. These results highlight a need for future research to validate the PST as a measure of basal ganglia reward learning. Keywords Individual differences . Addiction . Personality . Midbrain dopamine system . Basal ganglia . Reinforcement learning . Decision making . Probabilistic selection task Neuroimaging studies reveal that normal performance on decision making tasks is associated with widespread activations of the basal ganglia, midbrain dopamine system, and connected structures. These neural pathways are integral components of complex functional neuroanatomical loops underlying reinforcement learning and decision-making that appear critical for several cognitive, motor, and emotional Seeberger, & O'Reilly, 2004;Maia & Frank, 2011; Moustafa, Cohen, Sherman, & Frank, 2008; Moustafa, Sherman, & Frank, 2008;Solomon, Smith, Frank, Ly, & Carter, 2011;Steele, Kumar, & Ebmeier, 2007;Waltz, Frank, Robinson, & Gold, 2007;Waltz, Frank, Wiecki, & Gold, 2011;Wiecki & Frank, 2010) are associated with biases in basal ganglia function in such tasks, reflecting idiosyncratic differences in our abilities to learn and make choices. Yet the neural mechanisms that underlie individual differences in decision making remain poorly understood.According to an influential neurocomputational model of decision making, "the basal ganglia go/no-go model," dopaminergic signaling in the basal ganglia facilitates or suppresses action representations during reinforcement learning tasks: Phasic bursts of dopamine activity facilitate reward learning by reinforcing striatal connections that express D1 receptors (the "go/approach" pathway), whereas phasic dips in dopamine activity facilitate avoidance learning by reinforcing striatal connections that express D2 receptors (the "no-go/avoidance" pathway; Frank et al., 2004). Empirically, the model predictions are typically tested with the probabilistic selection task (PST), a trial-and-error learning task in which participants are required to learn three concurrent discrimi...

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“…They are expressed primarily in sub-cortical regions like the nucleus accumbens and caudate putamen where they are involved in the modulation of locomotion, reward, reinforcement, learning, and memory (e.g., Wise, 2004;Klein et al, 2007;Jocham et al, 2009;Frank and Fossella, 2011). Although the DRD4 receptor is also expressed in sub-cortical regions like the amygdala and the midbrain it is also amply located in the frontal cortex (e.g., Oak et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

The influence of dopaminergic gene variants on decision making in the ultimatum game

Reuter

Markett

Penz

et al. 2014

Personality and Individual Differences

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One of the most prominent paradigms in neuroeconomics is the ultimatum game (UG) that provides a framework for the study of pro-social behavior in two players interacting anonymously with each other: Player 1 has to split an endowment with player 2. Player 2 can either accept or reject the offer from player 1. If player 2 accepts the offer then the money is split as proposed by player 1. In case of rejection both players get nothing. Until now only one twin study investigated the heritability of the behavior in the UG. Results indicated a strong heritability for the decision behavior of player 2 whereas no genetic influence on player 1 behavior could be detected. Further studies are mandatory to validate these heritability estimates. However, a first candidate polymorphism, the DRD4 exon III, constituting the biological basis of the heritability in the responder behavior has already been identified in a Chinese sample . Until now genetic studies in Caucasians on the UG are lacking. The present study wants to fill this gap by investigating the UG in a healthy German sample. Moreover, we intend to find candidate genes that are associated with the first-mover-behavior. In a sample of N = 130 healthy participants an online version of the UG was conducted and polymorphisms of the dopamine D2 receptor gene (DRD2) and the DRD4 exon III VNTR were genotyped. We could confirm the DRD4 exon III effect on the responder behavior and the absence of an effect on the proposer behavior reported before. In line with Zhong et al. (2010) carriers of the 4/4 genotype showed a significant higher minimal acceptable offer (p = 0.023) than subjects with any other genotype. Furthermore, a DRD2-haplotype-block containing the single nucleotide polymorphisms rs1800497 and rs2283265 was significantly associated with the amount player1 offered (p = 0.005) but not with the decision of player 2. Results support the importance of the dopaminergic system for pro-social behavior.

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Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Cited by 170 publications

References 193 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

Constraints on decision making: Implications from genetics, personality, and addiction

The influence of dopaminergic gene variants on decision making in the ultimatum game

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