DRD2 Research Articles

Dose Effects of Histone Deacetylase Inhibitor Tacedinaline (CI-994) on Antipsychotic Haloperidol-Induced Motor and Memory Side Effects in Aged Mice.

Background: Elderly patients treated with antipsychotic drugs often experience increased severity and frequency of side effects, yet the mechanisms are not well understood. Studies from our group indicate age-related histone modifications at drug targeted receptor gene promoters may contribute to the increased side effects, and histone deacetylase (HDAC) inhibitors entinostat (MS-275) and valproic acid (VPA) could reverse typical antipsychotic haloperidol (HAL) induced motor-side effects. However, whether such effects could be dose dependent and whether HDAC inhibitors could improve memory function in aged mice is unknown.Methods: We co-treated selective class 1 HDAC inhibitor tacedinaline (CI-994) at different doses (10, 20, and 30 mg/kg) with HAL (0.05 mg/kg) in young (3 months) and aged (21 months) mice for 14 consecutive days, then motor and memory behavioral tests were conducted, followed by biochemical measurements.Results: CI-994 at doses of 10 and 20 mg/kg could decrease HAL-induced cataleptic episodes but only 20 mg/kg was sufficient to improve motor coordination in aged mice. Additionally, CI-994 at 10 and 20 mg/kg mitigate HAL-induced memory impairment in aged mice. Biochemical analyses showed increased acetylation of histone marks H3K27ac and H3K18ac at the dopamine 2 receptor (D2R) gene (Drd2) promoter and increased expression of the Drd2 mRNA and D2R protein in the striatum of aged mice after administration of CI-994 at 20 mg/kg.Conclusions: Our results suggest CI-994 can reduce HAL-induced motor and memory side effects in aged mice. These effects may act through an increase of acetylation at the Drd2 promoter, thereby restoring D2R expression and improving antipsychotic drug action.

Molecular Biological Mechanism ofBletilla striata on Neuropsychiatric System by Network Pharmacology and Experimental Validation

Bletilla striata is a rare traditional Chinese medicine with protective effect for neuropsychiatric system. Nevertheless, the material basis and molecular mechanism of this effect remain unclear. By means of network pharmacology, five common neuropsychiatric targets for B. striata ingredients that can pass through the blood-brain barrier were conducted to probe the material basis and molecular mechanism of its neuropsychiatric protecting effects. Besides, the in vitro model of neurons injury was built to verify the effect of these ingredients on neurons. Results indicated that 8 active ingredients and 21 core targets were screened, and 9 groups of gene functional groups were screened by GO analysis. The KEGG pathway enrichment revealed that, 14 signal pathways were mapped and 6 REACTOME Pathways and 33 Wiki Pathways were also detected. Preliminary experimental verification demonstrated that, B. striata protected, maintained and enhanced neuronal cell activity and up-regulated the expression of DRD2 and GRM2 genes through dihydrophenanthrene compounds. From the above results, we speculated that B. striata may act on multi-target gene functional groups through multiple ingredients, resulting in various effects, thus achieving the purpose of protecting the neuropsychiatric system, as well as its functions. Our research findings also suggested that the experimental research method combining network pharmacology with experimental cell research is effective for quickly analyzing the material basis and molecular mechanism of B. striata in protecting the neuropsychiatric system and treating neuropsychiatric diseases.

BDNF Val66Met polymorphism is associated with negative symptoms in early-onset schizophrenia spectrum and other psychotic disorders

Background and ObjectivesTo investigate the clinical characteristics of adolescents with early-onset full psychotic disorders either with Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) or DRD2/ANKK1 Taq1A (rs1800497) polymorphisms. Method101 cases with early-onset schizophrenia (EOS) or other psychotic spectrum disorders (SSD) and 150 healthy controls were included in the current study. Using the Positive and Negative Symptom Scale (PANSS), patient subgroups were compared for their psychotic symptoms, age-onset, duration of untreated illness, and family history of psychiatric disorders. The real-time polymerase chain reaction (RT-PCR) was implemented for genotyping procedures. ResultsStudy groups and patient subgroups were similar regarding their sociodemographic characteristics (16.4 ± 2.6 years, 62.2% male for all participants). Results did not reveal any difference between patients and healthy controls for DRD2/ANKK1 Taq1A and BDNF Val66Met genotypes. Patients with A1A2 (Gly/Lys) allele reported higher rates of substance use compared to A2A2 (Glu/Glu) counterparts. Other clinical variables were found similar. EOS/SSD group with Val66Met heterozygote allele revealed lower levels of negative symptoms than Val/Val homozygotes. Conversely, the age onset of full psychotic disorder, total positive symptom score, and total general psychopathology score of PANSS were found comparable between Val/Met and Val/Val groups. In the logistic regression model, Glu/Lys genotypes remained significant for the presence of substance use. ConclusionThe interaction between substance use and the DRD2 gene should be investigated for the development of early-onset psychotic disorders. BDNF Val66Met polymorphism also could be a disease-modifying factor for the presence of negative symptoms.

Research on the Effects of Occupational Stress and the DRD2 Gene on the Psychological Health of Workers in the Xinjiang Desert Oil Field.

Background: This study investigated the relationship between occupational stress and the mental health of people working in oil fields in the arid desert environment of Xinjiang, and revealed the causal relationship between occupational stress and psychological disorders, while furthermore exploring the relationship between psychological disorders and genetic levels.Methods: The participants of this study included oil field company workers from the Xinjiang Petroleum Administration of Karamay City, Xinjiang, who underwent occupational health examinations. The Occupational Stress Inventory Revised Edition (OSI-R) was used to measure the occupational stress of the oil workers. The mental health status of oil workers was evaluated using the Symptoms Checklist-90.Results: Occupational tasks: The total scores of the personal strain and mental health questionnaires were positively correlated with somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, terror, paranoia, and psychosis (P < 0.05). Individual coping resources and the mental health total score was negatively correlated with somatization, obsessive-compulsive symptoms, interpersonal sensitivity, anxiety, hostility, terror, paranoia, and psychosis. The following factors were identified as mental health risk factors: female gender; age 45 and above (relative to ≤30 years old); high scores on the personal strain questionnaire; occupational stress; external effort; internal investment; and high effort-low return. The following factors were identified as protective factors for mental health: Han nationality; oil transportation (relative to drilling); individual resilience; and work returns. In respect to the abnormal psychological group and the normal psychological group, statistically significant differences were found in the distribution of genotypes and allele frequencies at the rs1800497 locus (P < 0.05). The depression and paranoia scores observed between different genotype groups at the rs1800497 locus were statistically significant (P < 0.05).Conclusions: This study shows that occupational stress and the D2 dopamine receptor (DRD2) gene have an impact on the mental health of oil field workers in the arid desert environment of Xinjiang. Effort-reward imbalance and occupational stress were identified as risk factors for mental health, while rewards for work were protective factors. Higher levels of occupational stress may lead to depression and other psychological disorders, adversely affecting mental health. In oil field operators in the arid desert environment of Xinjiang, the AA genotype of the DRD2 gene in the rs1800497 locus was identified as a genotype specific to susceptibility to mental health problems, and a correlation was found between the A allele and an increased risk of psychological problems. Therefore, it is necessary to devise relevant measures to alleviate occupational stress among oil workers and increase their job rewards, so as to improve their mental health.

Genetic predictors of destructive and constructive types of digital behavior among young people

Relevance. In the context of globalization, manifestations of extremism, negativism, aggression, asocial and dissocial behavior on the Internet tend to increase. However, biological determinants of destructive and constructive forms and transformations of users’ behavior are under debate.Intention – To study genetic predictors of digital behavior among young adults.Methodology. The study involved 115 people (51 males, 64 females) aged 18 to 22 years. In order to study the digital behavior, we used the author’s questionnaire “Strategies of digital behavior”. Molecular genetic analysis was performed through the DNA isolation from buccal epithelial cells. Statistical methods included comparative analysis, very simple structure method (VSS), principal component analysis, and ANOVA.Results and Discussion. It is shown that in most respondents active conditionally “constructive” digital behaviors prevail (45 %), active “destructive” and passive conditionally “constructive” digital behaviors are expressed almost equally (27 and 28 %, respectively). The active-destructive digital behavior is significantly more often observed in carriers of the combination of BDNF G/G, COMT G/A, and DRD2 T/T polymorphisms. For the constructive digital behaviors, neither biological determinants nor associations with the studied genes were observed.Conclusion. The above associations of COMT, BDNF, and DRD2 genes with the behavioral strategies of Internet users expand the existing knowledge about biological determinants of digital behavior.

Detection of six novel de novo mutations in individuals with low resilience to psychological stress.

Genetic bases of psychological stress resilience have been studied previously, but mechanisms and genetic variants which are involved in stress resilience are still unclear. The present study aimed to evaluate the associations between variants in dopaminergic pathway genes with stress resilience. Subjects of the present study were divided into four groups. Group A included persons with normal reactions to major life events stressors; group B included persons with an acute stress reaction to major life events stressor; group C included persons with normal reactions to Crises/catastrophes stressors, and group D included persons with an acute stress reaction to Crises/catastrophes stressors. DNA was extracted from the subject's blood, and the entire length of 14 genes DRD1, DRD2, DRD3, DRD4, DRD5, COMT, DBH, TH, MAOA, DDC, DAT, 5-HTT, BDNF, and GDNF were sequenced by automated sequencers ABI 3700. Results showed 24 point mutations in 12 genes, including 16 SNPs and six novel mutations, which were significantly correlated to low-stress resilience. Most of the SNPs were known as risk alleles in psychiatric disorders. Several associations were found between genetic variants and psychological characteristics. Findings suggest dopaminergic as an important pathway in stress and stress resilience also indicated shared genetic bases between low-stress resilience and several psychiatric disorders.

DRD2 and BDNF polymorphisms are associated with binge eating disorder in patients with weight regain after bariatric surgery.

The aim of this study was to analyze the association and susceptibility of Single Nucleotide Polymorphisms (SNPs) in the DRD2 and BDNF genes with BED in patients with weight regain in the postoperative period of bariatric surgery. One hundred and seventy-seven individuals who underwent bariatric surgery with weight regain were evaluated and divided into two groups according to the BED diagnostic. The individuals were submitted to an anthropometric evaluation, analysis of the presence of BED using a validated questionnaire, and blood collection for genotyping of the polymorphisms rs6265 (BDNF) and rs1800497 (DRD2) by real-time polymerase chain reaction (RT-PCR). The presence of wild-type alleles for rs1800497 (CC) and rs6265 (GG) was more frequent in patients without BED. Nevertheless, the presence of one or two variant alleles for rs1800497 (CT + TT) and rs6265 (GA + AA) was more frequent in patients with BED. The combination of the two studied SNPs prevailed in patients with BED. The presence of allele frequency of rs1800497 SNP in the DRD2 gene and rs6265 SNP in the BDNF gene, isolated and/or combined, indicated an additional risk for the development of BED in patients with obesity, especially in the context of weight regain. III (evidence obtained from the case-control analytic study).

Methylation quantitative trait locus rs5326 is associated with susceptibility and effective dosage of methadone maintenance treatment for heroin use disorder.

Opioid use disorder is a complicated brain disease with high heritability. The underlying mechanisms of the genetic underpinnings in the susceptibility and treatment response of opioid use disorder remain elusive. To reveal the potential associations of genotypes and gene methylations of dopaminergic system genes, as well as roles of them in opioid use disorder. In the present study, we detected the DNA methylation in the promoter regions of five representative dopaminergic system genes (DRD1, DRD2, SLC6A3, TH, and COMT) between 120 patients with heroin use disorder in methadone maintenance treatment (MMT) program and 111 healthy controls. The associations of 25 SNPs in the above genes and methylation of 237 CpG sites, known as methylation quantitative trait loci (mQTLs), were determined. Then, the correlations of the above mQTLs and traits of heroin use disorder were analyzed in a sample set of 801 patients with heroin use disorder and 930 healthy controls. Our results demonstrated that several mQTLs in the DRD1 and DRD2 genes were identified both in the heroin use disorder and healthy control groups. Interestingly, rs4867798-CpG_174872884 and rs5326-CpG_174872884 in the DRD1 gene were the unique SNP-CpG pairs in the patients with heroin use disorder. Furthermore, mQTL rs5326 was associated with the susceptibility and effective dosage of MMT for heroin use disorder, and demonstrated allele-specific correlation with the expression of the DRD1 gene in the human caudate. Our findings suggest that some mQTLs may be associated with traits of opioid use disorder by implicating the DNA methylation and gene expression.

Development and Validation of KASP Assays for the Genotyping of Racing Performance-Associated Single Nucleotide Polymorphisms in Pigeons.

Pigeon racing’s recent upturn in popularity can be attributed in part to the huge prize money involved in these competitions. As such, methods to select pigeons with desirable genetic characteristics for racing or for selective breeding have also been gaining more interest. Polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) for genotyping-specific genes is one of the most commonly used molecular techniques, which can be costly, laborious and time consuming. The present study reports the development of an alternative genotyping method that employs Kompetitive Allele Specific Polymerase Chain Reaction (KASP) technology with specifically designed primers to detect previously reported racing performance-associated polymorphisms within the LDHA, MTYCB, and DRD4 genes. To validate, KASP assays and PCR-RFLP assays results from 107 samples genotyped for each of the genes were compared and the results showed perfect (100%) agreement of both methods. The developed KASP assays present an alternative rapid, reliable, and cost-effective method to identify polymorphisms in pigeons.

Genotypes of ANKK1 and DRD2 genes and risk of metabolic syndrome and its components: A cross-sectional study on Iranian women

We aimed to investigate the association between polymorphism of DRD2/ANKK1 gene with MetS and its components. Women (n = 531, aged 19–50 years) from the North-west of Iran were included by cluster sampling method. Polymorphisms of ANKK1 and DRD2 genes were defined in the study population. D/D (OR: 3.16; 95%CI: 1.31−7.60) and I/D (OR: 1.76; 95%CI: 1.12−2.78) genotypes of DRD2 (rs1799732) increased risk of MetS compared to I/I genotype. The D/D genotype of DRD2 (rs1799732) increased odds of hypertriglyceridemia in the study population. T/T (OR: 6.72; 95%CI: 1.99−22.71) and C/T (OR: 4.42; 95%CI: 2.79−7.01) genotypes of ANKK1 (rs1800497) increased risk of MetS compared to C/C genotype. Also, C/T genotype increased the odds of HTN, high FBS, high TG and low HDL-C levels compared to C/C genotype. These polymorphisms can affect the MetS components via their relation to the signaling of dopaminergic pathways and eating behaviors.

Analysis of associations between pharmacodynamic genetic factors and antipsychotics’ effectiveness and safety in adolescents with acute psychotic episodes taking antipsychotics during a 28-day follow-up

Introduction. Antipsychotics are the main drugs for treatment of schizophrenia spectrum disorders. Pharmacodynamic genetic factors are being actively studied to improve the accuracy of antipsychotic selection based on pharmacogenetic testing.Purpose of this study: to establish associations of genetic polymorphisms of the DRD2, DRD3, DRD4, HTR2A, COMT, ZNF804A, and ANKS1B genes with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode during a 28-day follow-up.Materials and methods. The study included 68 adolescents with an established diagnosis of acute polymorphic psychotic disorder at the time of admission (F23.0-9 according to ICD-10). All patients received an antipsychotic as their main therapy. Patients were monitored for 28 days. The effectiveness of antipsychotics was assessed using the Children’s Global Assessment Scale (CGAS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I). The safety of pharmacotherapy was assessed using the UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS). From each patient we obtained a buccal scraped epithelium, extracted DNA from it by sorbent method and detected carriage of genetic polymorphisms DRD2 rs1800497 (C&gt;T), DRD3 rs6280 (C&gt;T), DRD3 rs324026 (C&gt;T), DRD4 rs1800955 (C&gt;T), HTR2A rs6313 (T&gt;C), COMT rs4680 (Val158Met, G&gt;A), ZNF804A rs1344706 (A&gt;C), ANKS1B rs7968606 (C&gt;T) by real-time PCR.Results. DRD2 rs1800497 T allele carriers had a stronger reduction in the PANSS subscore «Productive Symptomatics» on day 14 (Me=-7.0 [-9.0;-5.0] vs Me=-7.0 [-8.0;-2.0]; p=0.018) and day 28 of follow-up (Me=-11.0 [-9.0;-5.5] vs Me=-8.0 [-8.0;-2.0]; p=0.019). Also, greater improvement on the CGAS scale on day 14 of follow-up was seen in TC+CC HTR2A rs6313 carriers (Me=2.0 [1.0;3.0] vs. Me=2.0 [1.0;2.0]; p=0.029). DRD3 rs324026 homozygous carriers (TT) had a significantly lower SAS score (Me=0.5 [0.0; 1.0] vs. Me=1.0 [0.0; 5.0]; p=0.016) and UKU subscore «Neurological Disorders» on 28 days of antipsychotic therapy (Me=0.0 [0.0; 0.0] vs. Me=1.0 [0.0; 3.8]; p=0.005). DRD3 rs324026 TT carriers also had lower severity of akathisia according to the BARS scale. Carriers of the T DRD4 rs1800955 allele had a higher SAS scale score on day 28 of therapy compared with CC homozygotes (Me=1.0 [0.0;4.0] vs Me=0.0 [0.0;1.0]; p=0.036).Conclusion. The DRD2 rs1800497 was a predictor of better reduction of productive symptoms; HTR2A rs6313 demonstrated a similar association. The DRD2 rs1800497 polymorphic variant was a predictor of better reduction of productive symptomatology; HTR2A rs6313 demonstrated a similar association. DRD3 rs324026 and HTR2A rs6313 were associated with a lower frequency of neurological adverse reactions and akathisia. In contrast, carriers of the DRD4 rs1800955 were more prone to adverse reactions on pharmacotherapy.

Analysis of Selected Variants of DRD2 and ANKK1 Genes in Combat Athletes.

The level of physical activity is conditioned by many different factors, including, among others, the personality traits of a person. Important is the fact that personality traits are a moderately heritable factor and on the basis of the analysis of several genes, various lifetime outcomes can be predicted. One of the most important pathways influencing personality traits is connected to the dopaminergic system; hence, we decided to analyze the DRD2 PROM. rs1799732, DRD2 rs1076560, DRD2 Tag1D rs1800498, DRD2 Ex8 rs6276, DRD2Tag1B rs1079597 and ANKK1 Tag1A rs180049. The research group included 258 male athletes (mean age = 26.02; SD = 8.30), whereas the control group was 284 healthy male volunteers matched for age (mean age = 22.89; SD = 4.78), both of Caucasian origin and without history of substance dependency or psychosis. Genomic DNA was extracted from venous blood using standard procedures. Genotyping was conducted with the real-time PCR method. Differences in the frequency of the DRD2Tag1B rs1079597 gene polymorphism were found between people practicing combat sports and the control group, and the DRD2 PROM. rs1799732, DRD2 rs1076560, DRD2 Tag1D rs1800498, DRD2 Ex8 rs6276, DRD2Tag1B rs1079597 and ANKK1 Tag1A rs1800497 genotypes and allele frequencies in the studied sample did not differ between the analyzed groups. Hence, we considered these polymorphic places as an interesting area for the further search for unambiguous associations between personality traits and attitude towards physical effort.

Analysis of DRD2 Gene Polymorphism in the Context of Personality Traits in a Group of Athletes.

The presented study showed the relationship between dopamine receptor gene polymorphism and personality traits in athletes training in martial arts. Behavioral modulation resulting from a balance of the neurotransmitters dopamine and norepinephrine to inactivation of the dorsolateral prefrontal cortex and dysregulation of various pathways involved in attention and impulse control processes; Methods: The study was conducted among martial arts athletes. The study group included 258 volunteers and 284 controls. The genetic test was performed using the real-time PCR method; psychological tests were performed using standardized TCI questionnaires. All analyses were performed using STATISTICA 13. Results: Interaction between martial arts and DRD2 rs1799732 (manual) G/-(VIC/FAM)-ins/del and RD- Harm avoidance and Reward Dependence scale were demonstrated. In athletes, a lower Reward Dependence scale score was associated with the DRD2 rs1799732 (manual)-/-polymorphism compared to the control group. Conclusions: It seems justified to study not only genetic aspects related to brain transmission dopamine in martial arts athletes. In the studied athletes, the features related to reward addiction and harm avoidance are particularly important in connection with the dopaminergic reward system in the brain.

Association study of Catechol-O-Methyltransferase (COMT) rs4680 Val158Met gene polymorphism and suicide attempt in Mexican adolescents with major depressive disorder

Aim We analyzed the association between SLC6A4, DRD2, COMT and MAOA genes and suicide attempt (SA) in Mexican adolescent patients with major depressive disorder (MDD). Methods The sample included 197 adolescents (127 females and 70 males) with principal diagnosis of MDD. Among them, 63 patients had SA at least once and 134 had not SA. The mean age of patients with and without SA was 15 ± 1.4 and 14 ± 1.5 years, respectively. We analyzed the genotype and allele distribution between patients with and without SA of SLC6A4 (5HTTLPR/rs25531), DRD2 (rs6275), COMT (rs4680), and MAOA (uVNTR). Results We did not find genotype or allele association between SA and SLC6A4 (χ2=0.67, p = 0.71; χ2=0.07, p = 0.77, respectively), DRD2 (χ2=0.05, p = 0.97; χ2=0.003, p = 0.95), and MAOA (females: χ2=0.86, p = 0.64; χ2=0, p = 1/males: χ2=0.008, p = 0.92) genes. However, there were differences in genotype frequencies of COMT/rs4680 between patients with SA and without SA (χ2=11.17, p = 0.003). Also, we observed a high frequency of Met158 allele showing an increased risk of having presented at least one SA (χ2=10.6, p = 0.001; OR = 1.43; 95% CI, 1.17–1.74). Conclusions Our findings showed an association between low activity genotype and allele of Val158Met polymorphism of COMT gene and SA in Mexican adolescents with MDD.

Candidate Genes Encoding Dopamine Receptors as Predictors of the Risk of Antipsychotic-Induced Parkinsonism and Tardive Dyskinesia in Schizophrenic Patients.

(1) Introduction: Extrapyramidal disorders form the so-called extrapyramidal syndrome (EPS), which is characterized by the occurrence of motor disorders as a result of damage to the basal ganglia and the subcortical-thalamic connections. Often, this syndrome develops while taking medications, in particular antipsychotics (APs). (2) Purpose: To review studies of candidate genes encoding dopamine receptors as genetic predictors of development of AP-induced parkinsonism (AIP) and AP-induced tardive dyskinesia (AITD) in patients with schizophrenia. (3) Materials and Methods: A search was carried out for publications of PubMed, Web of Science, Springer, and e-Library databases by keywords and their combinations over the last 10 years. In addition, the review includes earlier publications of historical interest. Despite extensive searches of these commonly used databases and search terms, it cannot be ruled out that some publications were possibly missed. (4) Results: The review considers candidate genes encoding dopamine receptors involved in pharmacodynamics, including genes DRD1, DRD2, DRD3, and DRD4. We analyzed 18 genome-wide studies examining 37 genetic variations, including single nucleotide variants (SNVs)/polymorphisms of four candidate genes involved in the development of AIP and AITD in patients with schizophrenia. Among such a set of obtained results, only 14 positive associations were revealed: rs1799732 (141CIns/Del), rs1800497 (C/T), rs6275 (C/T), rs6275 (C/T) DRD2; rs167771 (G/A) DRD3 with AIP and rs4532 (A/G) DRD1, rs6277 (C/T), rs6275 (C/T), rs1800497 (C/T), rs1079597 (A/G), rs1799732 (141CIns/Del), rs1045280 (C/G) DRD2, rs6280 (C/T), rs905568 (C/G) DRD3 with AITD. However, at present, it should be recognized that there is no final or unique decision on the leading role of any particular SNVs/polymorphisms in the development of AIP and AITD. (5) Conclusion: Disclosure of genetic predictors of the development of AIP and AITD, as the most common neurological adverse drug reactions (ADRs) in the treatment of patients with psychiatric disorders, may provide a key to the development of a strategy for personalized prevention and treatment of the considered complication of AP therapy for schizophrenia in real clinical practice.

Impulsivity is affected by cognitive enrichment and links to brain gene expression in red junglefowl chicks

Despite reported findings, explanations for within-species variation in behavioural performance on cognitive tests are still understudied. Cognitive processes are influenced by environmental and genetic differences, where cognitive stimulation and monoaminergic systems are predicted to be important. To explore explanations for individual variation in impulsivity (a behaviour that is negatively correlated with inhibitory control), we experimentally altered the environment of red junglefowl, Gallus gallus , by exposing chicks from newly hatched to 9 weeks old to either (1) both environmental and cognitive enrichment, (2) environmental enrichment without additional cognitive enrichment or (3) neither environmental nor cognitive enrichment. Subsequently, we measured variation in impulsivity and brain gene expression of genes from the dopaminergic system ( DRD1 and DRD2 ) and serotonergic system ( 5HT2A, 5HT1B, 5HT2B, 5HT2C and TPH ). We focused on two aspects of impulsivity, impulsive action and persistence, and their reduction over time. Cognitively enriched chicks tended to have higher initial impulsive action and had higher initial persistence, and our environmentally enriched chicks had slower reduction of impulsive action over time. DRD2 (a dopamine receptor gene) had lower expression in environmentally enriched chicks. Variation in impulsive action tended to correlate with expression of TPH (a gene involved in serotonin synthesis), whereas persistence correlated with both TPH and the dopamine receptor gene DRD1 , and tended to correlate with the dopaminergic gene DRD2 , regardless of rearing treatment. These results indicate that both environment and links to neurobiology could explain initial individual variation in, and reduction of, impulsivity. Further, distinct neurobiological pathways appear to govern impulsive action versus persistence, supporting the suggestion that impulsivity is a heterogenic behaviour. • We studied effects of experimentally altered rearing experiences on impulsivity. • We measured two aspects of impulsivity: impulsive action and persistence. • Cognitive enrichment affected impulsivity and rate of inhibiting impulsivity. • Brain monoaminergic gene expression linked to both aspects of impulsivity. • Thus, both environment and neurobiology contribute to variation in impulsivity.

Effects of variation in dopaminergic genes on the level of aggression and emotional intelligence in adolescents with conduct disorder

It has been reported that altered dopaminergic neurotransmission may contribute to the development of aggressive behaviors and emotional intelligence (EI) impairment. However, less is known about the impact of polymorphisms in dopaminergic genes on the level of aggression and EI. Therefore, we aimed to investigate the association between the catechol-O-methyltransferase (COMT) rs6277 gene polymorphism and the dopamine 2 receptor (DRD2) rs4680 gene polymorphism as well as the level of aggression and EI in adolescents with conduct disorder. Participants were 144 adolescents with conduct disorder recruited at the youth sociotherapy centre. The Buss-Perry Aggression Questionnaire (BPAQ) was administered to record the level of aggression while the Popular Emotional Intelligence Questionnaire (PEIQ) and the Schutte Self-Report Inventory (SSRI) were used to assess EI. We found no significant associations between selected polymorphisms and the scores of BPAQ, PEIQ and SSRI. Our findings do not support the role of the COMT and the DRD2 gene polymorphisms in shaping aggressive behaviors and EI in adolescents with conduct disorder. Longitudinal studies on larger populations are needed to confirm these results.

SLC6A3 (DAT1) as a Novel Candidate Biomarker Gene for Suicidal Behavior.

It has been previously shown that the serotonin and dopamine neurotransmitter systems might influence the predisposition to suicidal behavior. This study aims to estimate the contribution of 11 polymorphisms in the genes SLC6A4 (5HTT), HTR1A, HTR2A, HTR1B, SLC6A3 (DAT1), DRD4, DRD2, COMT, and BDNF to suicidal behavior and severity of symptoms of depression and anxiety in the Russian population. The study was performed on 100 patients with repeated suicide attempts and 154 controls. We first found an association between SLC6A3 (DAT1) 40 bp VNTR locus and suicidal behavior. This association was significant; when using the codominant (p = 0.006), dominant (p = 0.001), overdominant (p = 0.004), and log-additive (p = 0.004) models, LL genotype played a protective role (OR = 0.48, 0.29–0.82, p = 0.005). Difference in the distribution of COMT rs4680 genotypes was significant in the codominant (p = 0.04), dominant (p = 0.013), and log-additive (p = 0.02) models, and AA genotype might protect against suicide (OR = 0.49, 0.26–0.91, p = 0.025). SLC6A4 5-HTTLPR + rs25531 locus was significant in the recessive model (p = 0.024), and also affected the severity of symptoms of depression (p = 0.044) and personal anxiety (p = 0.029). Our results suggest that allelic variants of SLC6A3, COMT, and SLC6A4 genes might be considered as risk factors for suicidal attempts.

Genetic polymorphisms are associated with alterations in anxiety levels and vital signs in patients undergoing third molar extractions

The objective of this study was to evaluate the association between SLC6A4 (rs1042173 and rs3813034), DRD2 (rs6275 and rs6276), ANKK1 (rs1800497), and COMT (rs174675) genetic polymorphisms and alterations in anxiety levels and vital signs in individuals undergoing third molar extractions. One hundred sixty-eight individuals were evaluated at the pre-, trans-, and postoperative periods by checking systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and body temperature. Anxiety levels were assessed using the State-Trait Anxiety Inventory (STAI). Buccal mucosa cells were collected for genetic evaluation using real-time polymerase chain reaction. Statistical analysis was performed at a significance level of 5%. The level of anxiety was associated with rs1800497 for STAI-Trait (P=.031) and rs174675 for STAI-State (P=.007). Considering the vital signs, there was a significant difference between the values of respiratory rate and rs1042173 (P=.029), rs3813034 (P=.024), and rs6275 (P=.025). The diastolic blood pressure values differed significantly for rs1042173 (P=.042), and the body temperature values differed significantly for rs174675 (P=.016). Polymorphisms in SLC6A4, DRD2, ANKK1, and COMT genes could be associated with alterations in anxiety levels and vital signs in individuals undergoing third molar extractions.

Central Injection of Ghrelin Improves Motor Balance in the Rotarod Test in the Rats: Altering the Expression of Drd1 Gene

Introduction: Motor learning consolidates in adulthood, and its defects begin to appear with aging. Ghrelin, an endogenous peptide, improves memory and learning, targeting dopaminergic circuits. While cytidine diphosphate choline (citicoline) is known as a common drug for enhancing memory and learning in aging, it is not recommended for adults due to its side effects. The current study aimed at investigating if ghrelin treatment would improve motor learning via the expression of a relevant gene. Methods: For this experimental study, adult male Wistar rats were randomly divided into five groups: control group, three groups of ghrelin treatment (0.3, 1.5, and 3 nmol/μL), and one group with citicoline treatment. The injections were done intra-hippocampally. The motor learning rate was determined using the rotarod performance test by measuring the resistance to falling. Then the expression of dopamine receptor type D1 (Drd1) gene in the hippocampus was measured by a real-time polymerase chain reaction (PCR). Results: Ghrelin (3 nmol/μL) and citicoline had similar and significant effects on motor learning improvement (P&lt;0.01). Both drugs significantly increased Drd1 gene expression (P &lt;0.001). Conclusion: Ghrelin, like citicoline, improves motor learning by altering the expression of Drd1 gene in the hippocampus.