Many factors are involved in addiction. The dopaminergic system is thought to be the key element in this process. The mesolimbic dopamine system is a crucial element in the reward system. Changes in this system are thought to be leading to substance use disorders and dependence. Therefore, for our study we chose an analysis of two polymorphisms in genes (Variable Number of Tandem Repeats in DRD4 and DAT1) responsible for dopaminergic transmission, which might be implicated in the scores of personality traits measured by the NEO-FFI test. The study group consisted of 600 male volunteers—299 addicted subjects and 301 controls. Both groups were recruited by psychiatrists; in the case group addiction was diagnosed; in the controls a mental illness was excluded. In both groups the same psychometric test and genotyping by the PCR VNTR method were performed. The results were investigated by a multivariate analysis of the main effects ANOVA. In the presented study no DRD4 main effects were found for any of the analyzed traits but the DRD4 main effects approximated to the statistical significance for the extraversion scale. However, no DAT1 main effects were found for any of the analyzed traits but the DAT1 main effects approximated to the statistical significance for the agreeability scale.These associations open new possibilities for addiction research.
The susceptibility to cannabis dependency results from the influence of numerous factors such as social, genetic, as well as epigenetic factors. Many studies have attempted to discover a molecular basis for this disease. However, our study aimed at evaluating the connection between altered methylation of the dopamine transporter gene (DAT1) promoter CpG sites and cannabis dependency. In the cases of some DNA sequences, including the DAT1 gene region, their methylation status in blood cells may reflect a systemic modulation in the whole organism. Consequently, we isolated the DNA from the peripheral blood cells from a group of 201 cannabis-dependent patients and 285 controls who were healthy volunteers and who were matched for age and sex. The DNA was subjected to bisulfite conversion and sequencing. Our analysis revealed no statistical differences in the general methylation status of the DAT1 gene promoter CpG island between the patients and controls. Yet, the analysis of individual CpG sites where methylation occurred indicated significant differences. These sites are known to be bound by transcription factors (e.g., SP1, p53, PAX5, or GR), which, apart from other functions, were shown to play a role in the development of the nervous system. Therefore, DAT1 gene promoter methylation studies may provide important insight into the mechanism of cannabis dependency.
Presently, a growing popularity of electronic cigarettes may be observed. Used as a means of obtaining nicotine they allow to substitute traditional cigarettes. The origins of substance use disorders are conditioned by dopaminergic signaling which influences motivational processes being elementary factors conditioning the process of learning and exhibiting goal-directed behaviors. The study concentrated on analysis of three polymorphisms located in the dopamine receptor 2 (DRD2) gene—rs1076560, rs1799732 and rs1079597 using the PCR method, personality traits determined with the Big Five Questionnaire, and anxiety measured with the State Trait Anxiety Inventory. The study was conducted on a group of 394 volunteers, consisting e-cigarette users (n = 144) and controls (n = 250). Compared to the controls the case group subjects achieved significantly higher scores in regard to the STAI state and the trait scale, as well as the NEO-FFI Neuroticism and Openness scale. Likewise, in the case of the STAI state for DRD2 rs1076560 significant differences were found. Furthermore, while comparing the groups (e-cigarette users vs. controls) we noticed interactions for the NEO FFI Neuroticism and DRD2 rs1076560. The same was observed in the case of interactions significance while comparing groups (e-cigarette users vs. controls) for the STAI trait/scale and DRD2 rs1799732. Findings from this study demonstrate that psychological factors and genetic determinants should be analyzed simultaneously and comprehensively while considering groups of addicted patients. Since the use, and rapid increase in popularity, of electronic cigarettes has implications for public health, e-cigarette users should be studied holistically, especially younger groups of addicted and experimenting users.
Periodontal diseases are multiperspective problems resulting from numerous and diverse exposures that influence the process of initiation or progression of disease. The negative influence of tobacco smoking on oral health is well documented. The aim of the study was to analyze three SNPs in vitamin D receptor gene—rs7975232 (ApaI), rs2228570 (FokI) and rs1544410 (BsmI)—combined with oral health assessment—pH, gingival index, dry mouth, periodontitis, dry socket, redness of oral cavity mucosa, leukoplakia—in a group of cigarette smokers and in non-smokers. Moreover, the possibility of interactions between these polymorphisms and smoking was examined. When comparing the smokers and non-smokers groups, we noticed that rs1544410 heterozygotes were significantly more frequent in the first group, and for the second, both homozygotes were more frequent. Additionally, we observed the impact of interaction between the rs7975232 genotype and smoking status on gingival index. Current smoking was also associated with all analyzed oral health measures except for leucoplakia. Correlation between pH and age in both smokers and non-smokers was also present. Results of our analysis indicate that in our study group lifestyle and aging were leading factors associated with worse oral health status. However, the impact of genetic variants, and also the impact of their interaction with smoking on analyzed parameters was also visible. These results show great possibilities for all levels of prevention of oral diseases by means of education based on evidence-based medicine, but also for incorporating genetic testing and early interventions into this process for predisposed individuals.
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.
Development of an addiction is conditioned by many factors. The dopaminergic system has been shown to be the key element in this process. In this paper, we analyzed the influence of dopamine receptor 2 polymorphism rs1076560 in two groups—polysubstance-dependent male patients (n = 299) and the controls matched for age (n = 301). In both groups, we applied the same questionnaires for testing—Mini-international neuropsychiatric interview, the NEO Five-Factor Inventory, and the State–Trait Anxiety Inventory. The real-time PCR method was used for genotyping. When we compared the controls with the case group subjects, we observed significantly higher scores in the second group on both the state and trait scales of anxiety, as well as on the Neuroticism and Openness scales of the NEO-FFI; and lower scores on the scales of Extraversion and Agreeability of the NEO-FFI. The model 2 × 3 factorial ANOVA of the addicted subjects and controls was performed, and the DRD2 rs1076560 variant interaction was found for the anxiety state and trait scales, and for the NEO-FFI Neuroticism scale. The observed associations allow noticing that analysis of psychological factors in combination with genetic data opens new possibilities in addiction research.
Background: There has been a noticeable and systematic growth of the use of psychoactive substances over the past few decades. Dual diagnosis is a clinical term referring to the occurrence of psychoactive substance use disorder comorbid with another psychiatric disorder in the same person. The most common type of dual diagnosis is the co-occurrence of alcohol use disorder and mood disorders in the form of a depressive episode. Co-occurrent substance use disorders are frequently influenced by genetic factors. In selecting our area of research, we focused on dopamine and the DRD4 (Dopamine Receptor D4) gene polymorphism as well as associations with personality features. The aim of the study: The aim of the study was to compare DRD4 exon 3 (DRD4 Ex3) gene polymorphisms in patients diagnosed with polysubstance use disorder and co-occurrence of a depressive episode to DRD4 exon 3 gene polymorphisms in patients diagnosed with polysubstance use disorder and without co-occurrence of a depressive episode and a group of healthy volunteers. The study also aimed at establishing associations between personality features and DRD4 exon 3 gene polymorphisms of male patients diagnosed with polysubstance use disorder with co-occurrence of a depressive episode which may present a specific endophenotype of this group of patients. Methods: The study group comprised 602 male volunteers: patients diagnosed with polysubstance use disorder comorbid with a depressive episode (PUD MDD) (n = 95; mean age = 28.29, standard deviation (SD) = 7.40), patients diagnosed with polysubstance use disorder (PUD) (n = 206; mean age = 28.13, SD = 5.97), and controls (n = 301; mean age = 22.13, SD = 4.57). The patients and control subjects were diagnosed by a psychiatrist using the Mini International Neuropsychiatric Interview (MINI), the NEO Five-Factor Personality Inventory (NEO-FFI), and the State-Trait Anxiety Inventory (STAI) questionnaires. An analysis of the DRD4 exon 3 polymorphism was performed. Results: The patients diagnosed with PUD MDD compared to the control group of healthy volunteers showed significantly higher scores on both the STAI status and features scale and the NEO-FFI Neuroticism and Openness Scale, as well as lower scores on the Extraversion, Agreeableness, and Conscientiousness NEO-FFI scales. In the DRD4 exon 3 gene polymorphism, the s allele was more frequent in the PUD MDD compared to the l allele, which was less frequent. The results of the 2 × 3 factor analysis of variance (ANOVA) in patients and controls and the variant DRD4 exon 3 interaction were found on the Extraversion Scale and the Conscientiousness Scale of the NEO-FFI. Conclusions: The associations show that psychological factors combined with genetic data create a new area of research on addiction, including the problem of dual diagnosis. However, we want to be careful and draw no definite conclusions at this stage of our research.
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