DRD2 and ANKK1 genes associate with late-onset heroin dependence in men.

Objectives: Dopamine plays an important role in reward system of heroin dependence (HD), and dopaminergic D2 receptor (DRD2) gene is a candidate for the aetiology of HD. Ankyrin repeat and kinase domain containing 1 (ANKK1) gene is proximal to DRD2 and may influence its expression. We explored whether DRD2 and ANKK1 associate with occurrence of HD, and whether the genetic variants influence personality traits in male patients with HD.Methods:DRD2/ANKK1 polymorphisms were analysed in 950 unrelated Han Chinese male participants (601 HD patients and 349 healthy controls). All participants were screened using the same assessment tools and all patients met the diagnostic criteria of HD. Personality traits were assessed in 274 patients and 142 controls using the Tridimensional Personality Questionnaire.Results: According to the allele, genotype and haplotype frequency analysis, we observed an association between HD and several DRD2/ANKK1 polymorphisms (rs1800497, rs1800498, rs1079597 and rs4648319); this was most notable in the late-onset HD subgroup. However, these DRD2/ANKK1 polymorphisms did not associate with specific personality traits in HD patients and controls.Conclusions:DRD2/ANKK1 may play an important role in occurrence of late-onset HD, but does not mediate the relationship between personality traits and HD in Han Chinese male population.

OPRD1 gene affects disease vulnerability and environmental stress in patients with heroin dependence in Han Chinese.

Exposure to stress not only increases the vulnerability to heroin dependence (HD) but also provokes relapse. The etiology of HD and the role of life stress remain unclear, but prior studies suggested that both genetic and environmental factors are important. Opioid related genes, including OPRM1, OPRD1, OPRK1, and POMC, are obvious candidates for HD. Therefore, this study was conducted to explore whether the genetic polymorphisms of the candidates could affect vulnerability to HD and response to life stress in patients with HD. Ten polymorphisms of the opioid related genes were analyzed in 801 patients and 530 controls. The Life Event Questionnaire was used to assess the perspective and response to life stress in the past year. The genotype distribution and allelic frequency analyses showed that the minor C allele of rs2234918 in OPRD1 is over-represented in the HD group (P = .006 and P = .002, respectively). This finding was further confirmed by logistic regression analysis, showing that C allele carriers have a 1.42 times greater risk for HD compared to T/T homozygotes. A subgroup of 421 patients and 135 controls were eligible for life stress assessment. Patients with HD have a higher occurrence of negative events (No), negative events score (Ns), and average negative event score (Na) than those of controls (all P < .001), but there was no difference regarding positive recent events between the two groups. Gene-stress assessment in the HD group showed that T/T homozygotes of OPRD1 rs2236857 have more severe stress than C allele carriers (Ns, P = .004 and Na, P = .047). Our results indicate that the OPRD1 gene may not only play a role in the pathogenesis of HD but also affect the response to life stress among patients with HD in our Han Chinese population. Patients with the risk genotype may need additional psychosocial intervention for relapse prevention.

NGF gene polymorphisms are not associated with heroin dependence in a Taiwanese male population.

BACKGROUND AND OBJECTIVES: Heroin dependence (HD) is a chronic relapsing brain illness with substantial heritability. Nerve growth factor (NGF) is a crucial modulator in the neurodevelopment, and may be a key mediator of reward processes in HD. The purpose of this genetic study was to investigate whether NGF gene polymorphisms associate with the occurrence of HD and the specific personality traits of patients with HD. METHODS: We selected a homogeneous Han Chinese male population to overcome possible confounding effects of population and gender. For the study, 272 HD patients and 141 controls completed the Tridimensional Personality Questionnaire to evaluate their personality traits. In addition, a further sample 303 HD patients and 204 controls was added (with totally 920 participants) for the gene association and genotype-phenotype interaction studies. RESULTS: Patients with HD had higher novelty seeking (NS) and harm avoidance (HA) scores than healthy subjects. Nonetheless, NGF gene polymorphisms did not associate with specific personality traits in HD patients and controls. There is no significant difference in NGF gene polymorphisms between patients with HD and controls. DISCUSSION AND CONCLUSIONS: The NGF gene may neither contribute to the risk of development of HD, nor mediate the relationship between specific personality traits and HD in Han Chinese male population. SCIENTIFIC SIGNIFICANCE: Patients with HD had higher novelty seeking (NS) and harm avoidance (HA) scores than healthy subjects. However, none of the polymorphisms in the NGF gene affected the NS and HA scores in both patients and healthy subjects. (Am J Addict 2018;27:516-523).

Differential effect of the DRD3 genotype on inflammatory cytokine responses during abstinence in amphetamine-dependent women.

Amphetamine exposure impacts on innate and adaptive immunity and DRD3 may modulate the effect of amphetamine on the immune response. We assessed the immune-cytokine markers in 72 female patients with amphetamine dependence (AD) at baseline and after 4-week drug abstinence and in 51 healthy women. Multiplex magnetic bead assay was used to measure the plasma cytokine expression level simultaneously in all participants and DRD3 rs6280 polymorphism was genotyped in patients. We demonstrated an increase of the T helper 1 (Th1) cytokines (IL-2), Th2 cytokines (IL-4, IL-5, IL-6 and IL-10) and other cytokines (IL-1ß) in the entire AD cohort. A similar cytokine pattern, along with a significantly decreased IL-8 and IL-10 levels was observed after 4-week abstinence. Among AD patients with DRD3 rs6280 TT genotype, the cytokine expression profile was consistent with total AD cohort at baseline and revealed a significant down-regulated plasma level of the Th1, Th2, and other cytokines except for IL-6 after 4-week abstinence. In AD group with DRD3 rs6280 C allele carrier, we found IL-2 level was significantly higher than healthy controls at baseline and remained higher, accompanied with a borderline increase in IL-4, IL-6 and IL-1ß levels after 4-week abstinence. Our results suggest that chronic use of amphetamine increased both pro- and anti-inflammatory cytokines in AD patients, indicating the immune imbalance that may persist for 4 weeks or more. Besides, DRD3 rs6280 TT genotype may be associated with favorable recovery in general inflammatory cytokines during period of abstinence.

Olanzapine as a possible replacement choice for paliperidone-induced Pisa syndrome: a case report.

OBJECTIVE: The aim of this paper is to present a case of paliperidone-induced Pisa syndrome and provide treatment experience. METHOD: The case report is combined with a review of the literature. RESULTS: A 37-year-old man had been diagnosed with paranoid-type schizophrenia for about 10 years. He received three-month treatment of paliperidone extended release (ER) at 6 mg per day, but showed a progressively Pisa-like physical position. We initially added an anticholinergic drug, but saw no improvement. The paliperidone ER was replaced by olanzapine at 10 mg per day, and the Pisa-like symptom improved after 1 month of the drug replacement. CONCLUSIONS: We propose olanzapine as a possible replacement choice for patients with paliperidone-related Pisa syndrome.