This study analyzed genetic risk assessments in patients undergoing bariatric surgery to serve as a predictive factor for weight loss parameters 1 year after the operation. Thirty (30) patients were assessed for Genetic Addiction Risk Severity (GARS), which analyzes neurogenetic polymorphisms involved in addiction and reward deficiency. Genetic and psychosocial data collected before the operation were correlated with weight loss data, including changes in weight, body mass index (BMI), and percent of expected weight loss (%EWL). Results examined correlations between individual gene risk alleles, 1-year body weight data, and psychosocial trait scores. Spearman\'s correlations revealed that the OPRM1 (rs1799971) gene polymorphism had significant negative correlation with 1-year weight (rs = -0.4477, p < 0.01) and BMI (rs = -0.4477, p < 0.05). In addition, the DRD2 risk allele (rs1800497) was correlated negatively with BMI at 1 year (rs = -0.4927, p < 0.05), indicating that one risk allele copy was associated with lower BMI. However, this allele was positively correlated with both ∆Weight (rs = 0.4077, p < 0.05) and %EWL (rs = 0.5521, p < 0.05) at 1 year post-surgery. Moreover, the overall GARS score was correlated with %EWL (rs = 0.4236, p < 0.05), ∆Weight (rs = 0.3971, p < 0.05) and ∆BMI (rs = 0.3778, p < 0.05). Lastly, Food Cravings Questionnaire (FCQ) scores were negatively correlated with %EWL (rs = -0.4320, p < 0.05) and ∆Weight at 1 year post-surgery (rs = -0.4294, p < 0.05). This suggests that individuals with a higher genetic addiction risk are more responsive to weight loss treatment, especially in the case of the DRD2 polymorphism. These results should translate clinically to improve positivity and attitude related to weight management by those individuals born with the risk alleles (rs1800497; rs1799971).

Since 1990, there have been thousands of published studies on addiction psychiatry. Several from Blum et al showed the clinical relevance of the Genetic Addiction Risk Severity (GARS) test in identifying risk for reward deficiency behaviors in cohorts from polysubstance abuse and pain clinics, post-surgical bariatrics, and DWI offenders facing prison time. Since Blum et al first published in JAMA (1990) concerning the association of the DRD2 gene polymorphism and severe alcoholism, reactions have been mixed. More recently, however, a meta-analysis of 62 studies showed a significant association between DRD2 rs1800497 and Alcohol Use Disorder (AUD). Other studies from Yale University showed that a haplotype block of the DRD2 gene A1 allele was associated with AUD and heroin dependence. GWAS studies of depression and suicide in 1.2 million veterans confirmed the first psychiatric candidate gene study finding from Blum et al 1990; a significant association between the minor DRD2 allele, Taq A1 and severe alcoholism. Additionally, the DRD2 rs1800497 is robustly associated with suicidal behaviors. Furthermore, DNA polymorphic alleles underlying substance use disorder (SUD) with multiple substances were mapped via chromatin refolding, revealing that the DRD2 gene and associated polymorphism(s) as the top gene signal. Based on these investigations, we conclude that GWAS should end the controversy about the DRD2 gene being one determinant of Reward Deficiency Syndrome (RDS) first reported in 1996.

Since 1990, published addiction psychiatry articles have exceeded 11,495. Several from Blum et al. showed the clinical relevance of the Genetic Addiction Risk Severity (GARS) test in identifying risk for reward deficiency behaviors in cohorts from polysubstance and pain clinics, post-surgical bariatrics, and DWI offenders facing prison time. Since Blum et al first published in JAMA (1990) concerning the association of the DRD2 gene polymorphism and severe alcoholism, confirmation has been mixed and controversial. More recently, however, a meta-analysis of 62 studies showed a significant association between DRD2 rs 1800497 and Alcohol Use Disorder (AUD). Other studies from Yale University showed that a haplotype block of the DRD2 gene A1 allele was associated with AUD and heroin dependence. GWAS studies of depression and suicide in 1.2 million veterans confirmed the first psychiatric candidate gene study finding from Blum et al. 1990; a significant association between the minor DRD2 allele, Taq A1 (rs 1800497 C>T) and severe alcoholism. Additionally, the DRD2 rs1800497 is associated with suicide behaviors robustly at P=1.77 × 10-7. Furthermore, DNA polymorphic alleles underlying SUD with multiple substances were mapped via chromatin refolding, revealed that the DRD2 gene and associated polymorphism(s) was the top gene signal (DRD2, P=7.9 × 10-12). Additionally, based on these investigations, we conclude that GWAS should end the controversy about the DRD2 gene being at least one determinant of Reward Deficiency Syndrome (RDS) first reported in the Royal Society of Medicine journaling 1996.

Dopamine receptor D2 (DRD2) and ankyrin repeat and kinase domain-containing protein 1 (ANKK1) genes have received considerable attention for their involvement in alcohol use disorder (AUD), but many questions remain on their exact role. We conducted a population-based case-control and genetic association study in a large sample of young adults. Our aim was to assess the association between DRD2 and ANKK1 single nucleotide polymorphisms (SNPs) and harmful alcohol use, disentangling associated and possible intermediate factors. A total of 1841 college students from the French region Champagne-Ardennes, aged between 18 and 21 years and who reported at least one lifetime alcohol consumption, were included in this study. Allele frequencies were analysed according to harmful alcohol use (assessed through the Alcohol Use Disorder Identification Test [AUDIT] questionnaire). Different substance use disorders, including nicotine and cannabis dependences, were also assessed through questionnaires, as was a list of potential associated factors (e.g., major depressive episode, conduct disorder, attention-deficit/hyperactivity disorder [ADHD], school failure, sugar consumption, sexual trauma, parents\' use of alcohol, tobacco or cannabis). We found that DRD2 rs1800498 was associated with harmful alcohol use. Many factors were detected, but a global path analysis revealed that DRD2 rs1800498 had a significant direct effect on harmful alcohol use and that early age at first alcohol consumption and depressive symptoms moderated this effect. This study suggests an interplay between harmful alcohol use, DRD2 genotypes and other risk factors that, with a full understanding, could be useful for preventive purposes.

Compared to other addictive substances, patients with cannabis addiction are significantly outnumbered by those who report dependence on other, more addictive substances. Unfortunately, most cannabis addiction goes untreated, and among those who choose treatment, the requirements are much higher for adolescents and young adults.
To examine the relationship of cannabinoid dependency in the genetic context-the association between the rs1799732 polymorphism of the DRD2 gene and psychological traits and anxiety.
The study group consisted of 515 male volunteers. Of these, 214 patients were diagnosed with cannabis addiction and 301 were non-addicted. Patients were diagnosed with NEO Five-Factor Personality Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI) questionnaires. The interactions between personality traits and polymorphisms in the DRD2 rs1799732 gene were investigated in a group of cannabis-addicted patients and non-addicted controls using the real-time PCR method.
Compared to the control group, the case group obtained significantly higher scores on the STAI State, STAI Trait, Neuroticism and Openness scales, as well as lower scores on the Extraversion, Agreeableness, and Conscientiousness scales. There was no statistically significant difference between addicts and the control group in the frequency of genotypes, but there was a statistically significant difference between addicts and the control group in the frequency of the DRD2 allele rs179973. The multivariate ANOVA analysis showed a statistically significant influence of the DRD2 rs1799732 genotype on the NEO-FFI agreeableness scale and a statistically significant effect of addiction to cannabinoids or its absence on the NEO-FFI agreeableness scale score.
Studying homogeneous subgroups-as in our study-seems reasonable, particularly when combined with genetic determinants and psychological traits. In multigenic and multifactorial entities, such a strategy has a future.

UNASSIGNED: Repeated cocaine administration changes histone acetylation and methylation on Lys residues and Deoxyribonucleic acid (DNA) within the nucleus accumbens (NAc). Recently Nestler\'s group explored histone Arg (R) methylation in reward processing models. Damez-Werno et al. (2016) reported that during human investigations and animal self-administration experiments, the histone mark protein-R-methyltransferase-6 (PRMT6) and asymmetric dimethylation of R2 on histone H3 (H3R2me2a) decreased in the rodent and cocaine-dependent human NAc. Overexpression of PRMT6 in D2-MSNs in all NAc neurons increased cocaine seeking, whereas PRMT6 overexpression in D1-MSNs protects against cocaine-seeking.
UNASSIGNED: The hypothesis is that dopaminylation (H3R2me2a binding) occurs in psychostimulant use disorder (PSU), and the binding inhibitor Srcin1, like the major DRD2 A2 allelic polymorphism, protects against psychostimulant seeking behavior by normalizing nucleus accumbens (NAc) dopamine expression.
UNASSIGNED: Numerous publications confirmed the association between the DRD2 Taq A1 allele (30-40 lower D2 receptor numbers) and severe cocaine dependence. Lepack et al. (2020) found that acute cocaine increases dopamine in NAc synapses, and results in histone H3 glutamine 5 dopaminylation (H3Q5dop) and consequent inhibition of D2 expression. The inhibition increases with chronic cocaine use and accompanies cocaine withdrawal. They also found that the Src kinase signaling inhibitor 1 (Srcin1 or p140CAP) during cocaine withdrawal reduced H3R2me2a binding. Consequently, this inhibited dopaminylation induced a \"homeostatic brake.\"
UNASSIGNED: The decrease in Src signaling in NAc D2-MSNs, (like the DRD2 Taq A2 allele, a well-known genetic mechanism protective against SUD) normalizes the NAc dopamine expression and decreases cocaine reward and motivation to self-administer cocaine. The Srcin1 may be an important therapeutic target.

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.

Dopaminergic signaling within the striatum is crucial for motor planning and mental function. Neurons within the striatum contain two dopamine D2 receptor isoforms-D2 long and D2 short. The amount of expression for these receptor isoforms is affected by the genotype within two single nucleotide polymorphisms (SNPs), rs2283265 and rs1076560 (both are in high linkage disequilibrium; C > A), found in the DRD2 gene. However, it is unclear how these SNPs affect the distribution of D2 receptors in vivo within the nigrostriatal dopaminergic system. We aim to elucidate this with PET imaging in healthy young adults using [11C]-(+)-PHNO. Participants were genotyped for the DRD2 rs2283265 SNP and a total of 20 enrolled: 9 with CC, 6 with CA, and 5 with AA genotype. The main effect of genotype on [11C]-(+)-PHNO binding was tested and we found significant group effect within the ventral striatum. Specifically, CC and CA carriers had higher binding in this region compared to AA carriers. There were no observed differences between genotypes in other regions within the basal ganglia. Our preliminary results implicate that the polymorphism genotype affects the dopaminergic signaling by controlling either the quantity of D2 receptors, D2 affinity, or a combination thereof within the ventral striatum.

OBJECTIVE: The aim of the study was to determine relationships between the selected DRD2 gene polymorphisms and drug addiction.
METHODS: One hundred drug abusers undergoing treatment were recruited from the inpatient psychiatric centers in Poland. All participants were screened by means of the clinical interview SSAGA to describe the clinical picture. In the second part of the study, participants were examined using psychometric tools assessing selected psychopathological features. After that, blood samples were collected for a DNA isolation. The following DRD2 single nucleotide polymorphisms (SNPs) of the dopamine gene were genotyped: rs1800498 polymorphism of DRD2 gene (NC_000011.10:g.113420866G>A, GRCh38.p7); rs1079597 polymorphism of DRD2 gene (NC_000011.10:g.113425564C>T, GRCh38.p7); rs1076560 polymorphism of DRD2 gene (NC_000011.10:g.113412966C>A, GRCh38.p7).
RESULTS: The rs1800498 polymorphism has shown an association with drug abuse in which a higher frequency of the allelic T form was observed in the whole group of patients and selected subgroups with concomitant opiates or cannabis abuse history when compared with the controls.
CONCLUSIONS: In the presented study, one of selected polymorphisms of DRD2 gene, revealed to be correlated with substance use disorder (at the limit of statistical significance), which could suggest its impact on dependence endophenotype. The presented research was a pilot study, so it requires replication on a larger group of patients to verify and confirm obtained outcomes.

BACKGROUND: The aim of this study was to analyze the possible association of polymorphic variants of the DRD2 and ANKK1 genes with suicide attempt in a Mexican population.
METHODS: We conducted a case-control study in 289 subjects (166 suicide attempters and 123 healthy controls). We genotyped 2 polymorphisms of DRD2 (rs6275 and rs1799978) and 1 polymorphism of ANKK1 (rs1800497); then we analyzed the association between suicide attempt and these polymorphisms through genotypes, alleles, and inheritance models.
RESULTS: Individuals who carried the TT genotype of the rs1800497 showed a 3-fold risk of attempting suicide (OR = 3.01; 95% CI 1.56-5.81, p = 0.001) when evaluated through the recessive model. In an analysis stratified by gender, this risk factor remained present among females (OR = 2.81; 95% CI 1.37-5.75) as well as males (OR = 3.3; 95% CI 1.01-10.77).
CONCLUSIONS: Our results suggest that the rs1800497 variant of the ANKK1 gene could increase the risk of suicide attempt in a Mexican population. However, further studies using larger samples are necessary to obtain more conclusive results.