Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients.

Methadone, a synthetic racemic opioid that primarily works as a µ-opioid receptor (OPRM1) agonist, is commonly used for the treatment of heroin addiction. Genetic association studies have reported that the OPRM1 gene is involved in the physiology of heroin and alcohol addiction. Our current study is designed to test the hypothesis that genetic polymorphisms in the OPRM1 gene region are associated with methadone dosage, plasma concentrations, treatment responses, adverse reactions and withdrawal symptoms in a methadone maintenance treatment (MMT) cohort from Taiwan. Fifteen OPRM1 single nucleotide polymorphisms (SNPs) were selected and genotyped using DNA samples from 366 MMT patients. The plasma concentrations of methadone and its metabolite were measured by high performance liquid chromatography. The results obtained using dominant model analysis indicate that the OPRM1 SNPs rs1074287, rs6912029, rs12209447, rs510769, rs3798676, rs7748401, rs495491, rs10457090, rs589046, rs3778152, rs563649, and rs2075572 are significantly associated with change-in-libido side effects (adjusted p<0.042). Using recessive model analysis, these SNPs were also found to be significantly associated with insomnia side effects in this cohort (p<0.009). The significance of the insomnia findings was mainly contributed by a subgroup of patients who had a positive urine morphine test (p<0.022), and by individuals who did not use benzodiazepine hypnotics (p<0.034). Our current data thus suggest that genetic polymorphisms in OPRM1 may influence the change-in-libido and insomnia side effects sometimes found in MMT patients.

Genetic polymorphisms in CYP3A4 are associated with withdrawal symptoms and adverse reactions in methadone maintenance patients.

AIM: Methadone maintenance therapy is one of the standard treatments for heroin addiction. The isozyme CYP3A4 of the CYP system is one of the metabolic enzymes, as well as CYP2B6, responsible for the metabolism of methadone. The aim of the present study is to evaluate the potential use of genetic polymorphisms in CYP3A4 as biomarkers for the prediction of methadone treatment responses. MATERIALS & METHODS: A total of 366 Han Chinese methadone maintenance treatment patients in Taiwan were recruited in this study. Main clinical assessments included the clinical opioid withdrawal scale (COWS), the treatment emergent symptom scale (TESS) and the plasma concentrations of methadone and its metabolites. Genetic associations of six SNPs in the CYP3A4 gene were calculated using a general linear model. RESULTS: Genotypes and allele types of rs4646440 and rs2242480 were found to be significantly associated with the severity of withdrawal symptoms rated by COWS (p = 0.012, 0.0096, 0.017 and 0.012, respectively) as well as the side effects rated by TESS (p = 0.0089, 0.028, 0.0027 and 0.0085, respectively). The allele types associated with more severe withdrawal symptoms are also associated with more severe side effects and less betel nut (Areca catechu) use (p = 0.009 for rs4646440, p = 0.0063 for rs2242480). Further analyses on specific withdrawal symptoms in COWS showed that the genetic variants in rs4646440 are significantly associated with heart rate (allele type p = 0.0019). CONCLUSION: These results suggested that genetic variants in the CYP3A4 gene may be useful indicators for the severity of side effects and withdrawal symptoms for methadone treatment.

Positive attitudes and self-harming behavior of adolescents in a juvenile detention house in Taiwan.

This study aimed to evaluate the less stigmatizing positivity construct screening measurement and its association with recent self-harming behaviors among adolescents. Participants were 193 detained Taiwanese adolescents. Questionnaires consisted of a deliberate self-harm inventory, a positivity construct measurement, a depression scale, data concerning risky health behaviors and demographics. The prevalence rate of recent self-harming behavior among adolescents in the detention house was 43.5%. The logistic model showed that age, gender and level of positivity demonstrated significant odds ratios for self-harm behavior. Results showed that younger age and female gender increased self-harming behavior. In addition, low score on positivity construct screening measurement increased the probability of self-harming behavior. Furthermore, these adolescents also engaged in risky health behaviors and were more depressed. Parental and school awareness for these risky behaviors should be enhanced and appropriate early interventions implemented to prevent negative health outcomes.

Higher systemic inflammation is associated with poorer sleep quality in stable haemodialysis patients.

BACKGROUND: Increased inflammation has been noted in sleep disorder patients with normal renal function. However, the relationship between sleep quality and circulating inflammatory markers has not been previously studied in haemodialysis (HD) patients. METHODS: A total of 114 HD end-stage renal disease patients receiving maintenance HD for >3 months were included in this study. Pittsburgh Sleep Quality Index (PSQI) was used to measure individual's sleep quality. Based on the global PSQI score, patients were divided into groups of good sleepers (PSQI < 5) and bad sleepers (PSQI >or= 5). RESULTS: Twenty-three patients (20.2%) were classified as good sleepers and 91 patients (79.8%) were bad sleepers. Bad sleepers have significantly higher serum hsCRP level and lower serum phosphate level (all P < 0.05). The global PSQI score, or worse sleep quality are positively correlated with serum triglyceride level, high-sensitivity C-reactive protein (hsCRP) level, IL-1beta level and negatively correlated with the haemoglobin and phosphate level. In the multi-variable linear regression model, levels of hsCRP (beta = 0.209, P = 0.029) and triglyceride (beta = 0.212, P = 0.025) were both significant independent predictors for the global PSQI score. CONCLUSION: Our study demonstrated severe impairment of sleep quality in HD patients and corroborated the role of inflammation in the pathogenesis of sleep disturbance.