Individual differences in flow proneness are linked to a dopamine D2 receptor gene variant.

Flow is a special mental state characterized by deep concentration that occurs during the performance of optimally challenging tasks. In prior studies, proneness to experience flow has been found to be moderately heritable. In the present study, we investigated whether individual differences in flow proneness are related to a polymorphism of the dopamine D2 receptor coding gene (DRD2 C957T rs6277). This polymorphism affects striatal D2 receptor availability, a factor that has been shown to be related to flow proneness. To our knowledge, this is the first study to investigate the association between this trait and a specific gene variant. In a sample of 236 healthy Hungarian adults, we found that CC homozygotes report higher flow proneness than do T allele carriers, but only during mandatory activities (i.e., studying and working), not during leisure time. We discuss implications of this result, e.g., the potential mediators of the relationship.

Analysis of Dopamine Receptor D2 Gene Polymorphism and Correlation with Dyslipidemia in the Chinese Population.

Objective: The study aimed to explore the genotype and allele distributions of dopamine D2-like receptor (DRD2) gene -141C and C957T polymorphisms in the Chinese Han population with dyslipidemia, as well as their association with serum lipid levels. Methods: One hundred fifty patients with dyslipidemia and 150 healthy people were recruited as the case and the control groups, respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol levels were detected. The target sequence of DRD2 polymorphisms was amplified by polymerase chain reaction and genotyped via Sanger sequencing. Results: In DRD2 gene C957T (rs6277), three genotypes of CC, CT, and TT were detected with the frequencies of 92.67%, 6.67%, 0.67% in dyslipidemia cases, and 83.33%, 14.67%, 2.00% in the controls, respectively. The CT genotype and T allele frequencies were significantly low in the case group relative to the control group. After adjusting to other clinical indicators, the CT genotype of C957T polymorphism (hazard ratio = 0.401, 95% confidence interval = 0.181-0.890, p < 0.05) was still related to a significantly reduced risk of dyslipidemia. The C957T CT genotype carriers had the lowest values of serum TC, TG, LDL, and the highest values of serum HDL-C. Conclusion: DRD2 gene C957T polymorphism was an independent influencing factor associated with the susceptibility to dyslipidemia, and the CT genotype was associated with decreased odds of susceptibility to dyslipidemia.

Working memory gating in obesity is moderated by striatal dopaminergic gene variants.

Everyday life requires an adaptive balance between distraction-resistant maintenance of information and the flexibility to update this information when needed. These opposing mechanisms are proposed to be balanced through a working memory gating mechanism. Prior research indicates that obesity may elevate the risk of working memory deficits, yet the underlying mechanisms remain elusive. Dopaminergic alterations have emerged as a potential mediator. However, current models suggest these alterations should only shift the balance in working memory tasks, not produce overall deficits. The empirical support for this notion is currently lacking, however. To address this gap, we pooled data from three studies (N = 320) where participants performed a working memory gating task. Higher BMI was associated with overall poorer working memory, irrespective of whether there was a need to maintain or update information. However, when participants, in addition to BMI level, were categorized based on certain putative dopamine-signaling characteristics (single-nucleotide polymorphisms [SNPs]; specifically, Taq1A and DARPP-32), distinct working memory gating effects emerged. These SNPs, primarily associated with striatal dopamine transmission, appear to be linked with differences in updating, specifically, among high-BMI individuals. Moreover, blood amino acid ratio, which indicates central dopamine synthesis capacity, combined with BMI shifted the balance between distractor-resistant maintenance and updating. These findings suggest that both dopamine-dependent and dopamine-independent cognitive effects exist in obesity. Understanding these effects is crucial if we aim to modify maladaptive cognitive profiles in individuals with obesity.

Interaction Effects of DRD2 Genetic Polymorphism and Interpersonal Stress on Problematic Gaming in College Students.

Problematic gaming has become a public concern, influenced both by genetic factors and stressful environments. Studies have reported the effects of dopamine-related genes and interpersonal stressors on problematic gaming, but gene and environment interaction (G × E) studies have not been conducted. In this study, we investigated the interaction effects of dopamine receptor D2 (DRD2) polymorphisms and interpersonal stress on problematic gaming and the mediating effect of avoidant coping to reveal the mechanism of the G × E process. We recruited 168 college students (mean age = 22; male 63.1%) and genotyped their DRD2 C957T (rs6277) and Taq1 (rs1800497) polymorphisms. The results of the mediated moderation analysis showed that, when experiencing interpersonal stressors, individuals with both the C957T T allele and the Taq1 A1 allele showed more elevated problematic gaming scores than non-carriers. Moreover, the interaction effect of the combined DRD2 polymorphisms and interpersonal stress was significantly mediated by avoidant coping. These findings suggest that the influence of interpersonal stress on problematic gaming can be changed as a function of DRD2 genotypes, which may be because of the avoidant coping styles of C957T T allele and Taq1 A1 allele carriers in response to stress.

The relationship of age and DRD2 polymorphisms to frontostriatal brain activity and working memory performance.

Dopamine (DA) in both prefrontal cortex (PFC) and caudate nucleus is critical for working memory (WM) function. The C957T and Taq1A polymorphisms of the DRD2 gene are related to DA D2 receptor densities in PFC and striatum. Using functional MRI, we investigated the relationship of age and these 2 DRD2 gene polymorphisms to WM function and examined possible age by gene interactions. Results demonstrated less caudate activity for older adults (70-80 years; n = 112) compared with the younger age group (25-65 years; n = 191), suggesting age-related functional differences in this region. Importantly, there was a gene-related difference regarding WM performance and frontostriatal brain activity. Specifically, better WM performance and greater activity in PFC were found among C957T C allele carriers. Combined genetic markers for increased DA D2 receptor density were associated with greater caudate activity and higher WM updating performance. The genetic effects on blood oxygen level-dependent activity were only observed in older participants, suggesting magnified genetic effects in aging. Our findings emphasize the importance of DA-related genes in regulating WM functioning in aging and demonstrate a positive link between DA and brain activation in the frontostriatal circuitry.

The effect of ANKK1 Taq1A and DRD2 C957T polymorphisms on executive function: A systematic review and meta-analysis.

Research in healthy adults suggests that C957T polymorphism of the dopamine D2 receptor encoding DRD2 and the Taq1A polymorphism of the neighbouring gene ankyrin repeat and kinase domain containing 1 (ANKK1) alter dopaminergic signalling and may influence prefrontally-mediated executive functions. A systematic review and meta-analysis was carried out on the evidence for the association of DRD2 C957T and ANKK1 Taq1A polymorphisms in performance on tasks relating to the three core domains of executive function: working memory, response inhibition and cognitive flexibility in healthy adults. CINAHL, MEDLINE, PsycARTICLES and PsychINFO databases were searched for predefined key search terms associated with the two polymorphisms and executive function. Studies were included if they investigated a healthy adult population with the mean age of 18-65 years, no psychiatric or neurological disorder and only the healthy adult arm were included in studies with any case-control design. Data from 17 independent studies were included in meta-analysis, separated by the Taq1A and C957T polymorphisms and by executive function tests: working memory (Taq1A, 6 samples, n = 1270; C957 T, 6 samples, n = 977), cognitive flexibility (C957 T, 3 samples, n = 620), and response inhibition (C957 T, 3 samples, n = 598). The meta-analyses did not establish significant associations between these gene polymorphisms of interest and any of the executive function domains. Theoretical implications and methodological considerations of these findings are discussed.

Relationship between serum homovanillic acid, DRD2 C957T (rs6277), and hDAT A559V (rs28364997) polymorphisms and developmental stuttering.

The involvement of the brain dopamine system in the pathophysiology of developmental stuttering has been previously suggested. In the present study, we aimed to investigate the relationship between developmental stuttering in children and the levels of serum homovanillic acid (HVA), dopamine D2 receptor (DRD2) C957T (rs6277), and solute carrier family 6 member 3 (SLC6A3) human dopamine transporter (hDAT) A559V (rs28364997) single-nucleotide polymorphisms. In a case-control study, serum level of HVA, DRD2 C957T, and DAT A559V were compared between 85 children who stuttered (CWS) and 85 age- and sex-matched children who did not stutter (CWNS). Although serum level of HVA was higher among the CWS (median = 25.50 ng/mL) than that in the CWNS (median = 17.40 ng/mL), the difference between the two groups was not significant (p = 0.43). No significant correlation was observed between age and the level of HVA among all the participants (r = -0.15, p = 0.06), nor was there any correlation among the CWS (r = -0.19, p = 0.14) or among the CWNS (r = -0.13, p = 0.27) according to the Spearman correlation coefficient. On the other hand, there was a significant negative correlation between age from stuttering onset and the serum level of HVA among the CWS group (r = -0.32, p = 0.01). The Spearman correlation coefficient did not indicate any significant correlation between stuttering severity and HVA in CWS (r = -0.06, p = 0.59). The mutant allele of hDAT A559V was observed neither in the CWS nor in the controls. The allele frequencies of DRD2 C957T were not significantly different between the CWS and the CWNS; however, the frequency of the TT genotype was significantly higher among the CWS (p = 0.02), which was associated with 2.25-fold susceptibility to stuttering (OR = 2.25, 95% CI = 1.03 to 4.90, p = 0.04). Our findings suggest that the serum level of HVA might be a biomarker for dopaminergic involvement in the pathogenesis of stuttering. Moreover, the present study indicates that the DRD2 C957T polymorphism might be a risk factor for the development of stuttering among Iranian Kurdish population.

Behavioral and Neural Manifestations of Reward Memory in Carriers of Low-Expressing versus High-Expressing Genetic Variants of the Dopamine D2 Receptor.

Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2) availability in the striatum, and the DRD2 TaqIA (rs1800497) and C957T (rs6277) genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that the variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI) in 62 young, healthy individuals genotyped for DRD2 TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an intermediate phenotype of addiction memory.

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

INTRODUCTION: Previous 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. METHODS: One 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. CONCLUSIONS: This 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.

The relationship between DRD2 gene polymorphisms (C957T and C939T) and schizophrenia: a meta-analysis.

Schizophrenia is a common, complex multi-factorial psychiatric disorder. Many studies have reported associations between the C957T and C939T polymorphisms in Dopamine D2 receptor (DRD2) gene and schizophrenia, but results are inconsistent. To derive a more precise estimation of the relationship, a meta-analysis was conducted to systematically summarize the possibility. We included 13 articles involving 3079 schizophrenia cases and 3851 healthy controls. Positive associations were found between C957T polymorphism and schizophrenia risk in C vs. T (OR=1.26, 95% CI=1.09-1.46, Praw=0.002, PFDR=0.005) and CC+CT vs. TT (OR=1.47, 95% CI=1.25-1.73, Praw<0.001, PFDR<0.001). When stratified by race, a significantly increased risk of schizophrenia was observed in Caucasians, but not in Asians. No association between C939T polymorphism and schizophrenia was found in overall or Asian population. Our study suggested that C957T of DRD2 gene polymorphism is likely to be a risk factor for schizophrenia, especially in Caucasian.

The DRD2 C957T polymorphism and the attentional blink--a genetic association study.

The attentional blink phenomenon (AB) describes a transient deficit in temporally selective visual attention regarding the processing of the second of two target stimuli in a rapid serial visual presentation (RSVP) task. The AB is a very prominent paradigm in the Cognitive Neurosciences that has been extensively studied by diverse psychophysiological techniques such as EEG or fMRI. Association studies from molecular genetics are scarce although the high heritability of higher cognitive functioning is proven. Only one seminal study reported an association between AB magnitude and the dopamine receptor D2 (DRD2) C957T polymorphism (Colzato et al., 2011). This functional polymorphism influences striatal D2 receptor binding affinity and thereby the efficacy of dopaminergic neurotransmission which is important for working memory and attentional processes. Colzato et al. (2011) reported that DRD2 C957T T/T-carriers exhibit a significant smaller AB than C-allele carriers. In the present study this influence of the DRD2 SNP on the AB could not be replicated in N=211 healthy participants. However, a significantly larger lag 1 sparing was observed for homozygous T/T-carriers. Moreover, carriers of at least one T-allele showed a significantly poorer performance in the identification of T1. In general, these results support the notion of a role of the dopaminergic system on the AB. However, as our results do not parallel previous findings the exact nature of this influence and its dependence on task parameters will have to be examined in further genetic association studies.