Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.107 (DAT)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested human participants on a modified peak procedure in order to investigate the relation between interval timing and reward processing, and examine the interaction of this relation with three different dopamine-related gene polymorphisms. These gene polymorphisms affected the expression of catechol-o-methyltransferase, which catabolizes synaptic dopamine primarily in the prefrontal cortex (COMT Val158Met polymorphism), D2 dopamine receptors primarily in the striatum (DRD2/ANKK1-Taq1a polymorphism), and dopamine transporters, which clear synaptic dopamine in the striatum (DAT 3' VNTR variant). The inclusion of these polymorphisms allowed us to investigate dissociable aspects of the dopamine system and their interaction with reward magnitude manipulations in shaping timed behavior. These genes were chosen for their roles in reward processing and cortico-striatal information processing that have been implicated for interval timing. Consistent with recent animal studies, human participants initiated their timed anticipatory responding earlier when expecting a larger reward in the absence of any changes in the timing of response termination or perceived time. This effect however was specific to two out of four evaluated COMT and DRD2 polymorphism combinations that lead to high prefrontal dopamine coupled with high D2 density and low prefrontal dopamine coupled with low D2 density. Larger rewards also decreased timing precision indices, some of which interacted with the COMT polymorphism. Furthermore, the COMT polymorphism that leads to higher prefrontal dopamine resulted in weaker manifestation of memory variability (relative to threshold variability) in timed behavior. There was no effect of DAT polymorphisms on any of the core behavioral measures. These results suggest that the reward modulates decision thresholds rather than clock speed, and that these effects are specific to COMT and DRD2 epistasis effects that presumably constitute a balanced prefrontal and striatal dopamine transmission.
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PMID:Epistasis effects of dopamine genes on interval timing and reward magnitude in humans. 2290 38

We tested the differential susceptibility hypothesis with respect to connections between interactions in the family of origin and subsequent behaviors with romantic partners. Focal or target participants (G2) in an ongoing longitudinal study (N = 352) were observed interacting with their parents (G1) during adolescence and again with their romantic partners in adulthood. Independent observers rated positive engagement and hostility by G1 and G2 during structured interaction tasks. We created an index for hypothesized genetic plasticity by summing G2's allelic variation for polymorphisms in 5 genes (serotonin transporter gene [linked polymorphism], 5-HTT; ankyrin repeat and kinase domain containing 1 gene/dopamine receptor D2 gene, ANKK1/DRD2; dopamine receptor D4 gene, DRD4; dopamine active transporter gene, DAT; and catechol-O-methyltransferase gene, COMT). Consistent with the differential susceptibility hypothesis, G2s exposed to more hostile and positively engaged parenting behaviors during adolescence were more hostile or positively engaged toward a romantic partner if they had higher scores on the genetic plasticity index. In short, genetic factors moderated the connection between earlier experiences in the family of origin and future romantic relationship behaviors, for better and for worse.
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PMID:For better and for worse: genes and parenting interact to predict future behavior in romantic relationships. 2482 24

In the work there was performed an assessment of the interaction of microsocial and genetic factors of the development of psychoactive substance (PS) dependence. The objects of the psycho-hygienic and molecular-genetic studies were 538 male patients from the specialized diagnostic and treatment center at the age from 17 to 65 years with a diagnosis of "PS dependence" according to F10-F09 in the ICD-10. There were determined personality predictors of early (before 25 years) manifestation of systematic abuse, such as low self-control, individualisticity, authoritarianism, unjustified optimism and reduced capacity for social adaptation. Manifestation of the PS dependence at an early age (25 years) is determined by the contribution of genotype 9R+ DAT gene in the combination with other predisposing genotypes A1 + DRD2/ANKK1, SS SERT and 7R+ DRD. The risk of development of PS dependence at a more younger age increases with the superimposition of individual predisposing genotypes ranging from 1,2 (7R+ gene DRD4) to 1,9 (A1 + gene DRD2/ANKK10 on a destructive milieu. Pairwise combinations of genotypes 7R+ DRD4 x A1+ DRD2, 7R+ DRD4 x 9R+ DAT, 9R+ DAT x A1+ DRD2, 9R+ DAT x SS SERT significantly increase the risk by 2 or more times (2.5-2.8). There was suggested an algorithm for the prenosological forecast of the development of PS dependence in adolescents and young men.
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PMID:[Modern approaches to the primary prevention of the development of psychoactive substance dependence on the base of accounting of environmental and genetic risk factors]. 2505 44

Background: Approximately 25-50% of people diagnosed with substance use disorder experience psychiatric disorders, and this percentage is even higher if subclinical psychopathological symptomatology is taken into consideration. "Dual diagnosis" implies the comorbidity of two disorders (mental disorder and addiction), but in a clinical setting, numerous dual diagnoses involve multiple addictions (polysubstance use means the concurrent use of more than one psychoactive substance). Clinical observations and epidemiological studies showed that the use of stimulants in combination with other substances results in additional risks. Apart from the clinical significance of the specificity of stimulants used in combination with other substances, only non-exhaustive research on the specificity of this comorbidity has been performed to date. The aim of the study was to analyze polymorphisms of the genes (DRD4 VNTR in exon III Ex3, DRD2 rs1076560, rs1800498, rs1079597, rs6276, as well as in the PROM promoter region (rs1799732, ANKK1 Tag1A rs1800497, DAT) in a group of patients diagnosed with polysubstance use disorder, including addiction to stimulants, and the co-occurrence of specific mental disorders in a group of patients diagnosed with polysubstance use disorder, including addiction to stimulants, compared to the group of patients diagnosed with polysubstance use disorder. Methods: The study group consisted of 601 male volunteers with psychoactive substance dependence (n = 300) and non-dependent controls (n = 301). The genomic DNA was extracted from venous blood using standard procedures. Genotyping was conducted with the real-time PCR method. All computations were performed using STATISTICA 13. Results: Psychotic disorders were significantly more common in the group of males with polysubstance addiction, including addiction to stimulants, compared to the group of males with polysubstance addiction without addiction to stimulants. In our own research, different statistical significances were found in the frequency of the DRD4 Ex3 gene polymorphism: s/s was more common in the study group. Psychotic disorders were more common in people addicted to stimulants compared to people addicted to other substances. Conclusions: In our study, psychotic disorders occurred more frequently in the study group of patients with polysubstance addiction, including addiction to stimulants, compared to the control group of patients with polysubstance addiction, but with no addiction to stimulants. Different statistical significances were found in the frequency of the DRD4 Ex3 gene polymorphism: s/s was more common in the study group, while the l/l genotype was less frequent in the study group. In DRD2 PROM rs 1799732, the del allele occurred more often than the ins allele in the study group. In the DRD4 Ex3 gene polymorphism, the s allele was more common in the study group, and the l allele was less frequent. In the DRD4 Ex3 gene polymorphism for the s/s genotype, psychotic disorders and generalized anxiety were more common, while for the s/l and l/l genotype, they were less frequent. The DRD4 Ex3 polymorphism s alleles were more common for depressive episode, dysthymia, and psychotic disorders as well as generalized anxiety disorder. We see a clear genetic aspect here. However, we want to be careful and draw no definite conclusions.
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PMID:DRD4, DRD2, DAT1, and ANKK1 Genes Polymorphisms in Patients with Dual Diagnosis of Polysubstance Addictions. 3317 85