The association of genetic polymorphisms in the κ-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance.

Methadone is a synthetic opioid that binds to the κ-opioid receptor with a low affinity. This study tested the hypotheses that the genetic polymorphisms in the κ-opioid receptor 1 (OPRK1) gene region are associated with methadone treatment responses in a Taiwan methadone maintenance treatment (MMT) cohort. Seventeen single nucleotide polymorphisms (SNPs) in OPRK1 were selected and genotyped on DNA of 366 MMT patients. Six SNPs from rs7843965 to rs1051660 (intron 2 to exon 2) were significantly associated with body weight (P < 0.007). A haplotype of 4 SNPs rs7832417-rs16918853-rs702764-rs7817710 (exon 4 to intron 3) was associated with bone or joint aches (P ≤ 0.004) and with the amount of alcohol use (standard drinks per day; global P < 0.0001). The haplotype rs10958350-rs7016778-rs12675595 was associated with gooseflesh skin (global P < 0.0001), yawning (global P = 0.0001), and restlessness (global P < 0.0001) withdrawal symptoms. The findings suggest that genetic polymorphisms in OPRK1 were associated with the body weight, alcohol use, and opioid withdrawal symptoms in MMT patients.

OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: a cross sectional study.

Majority of the heroin-dependent patients smoke cigarettes. Although it has been reported that the OPRM1 genetic polymorphism is associated with the brain mu-opioid receptor binding potential in cigarette smokers, there is no direct evidence showing the impact of plasma cotinine, a nicotine metabolite, on treatment responses to methadone maintenance treatment (MMT). In this study, we aimed to test the hypothesis that the genetic polymorphisms in the OPRM1 are associated with the methadone treatment responses and the severity of cigarette smoking directly measured by the plasma concentration of cotinine in a Taiwanese MMT cohort. Fifteen OPRM1 single-nucleotide polymorphisms (SNPs) were selected and genotyped on DNA samples of 366 MMT patients. Plasma concentrations of cotinine were measured by cotinine enzyme-linked immunosorbent assay. The plasma cotinine concentration had positive correlation with concentrations of methadone (P = 0.042) and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine (P = 0.037). Methadone treatment non-responders, defined by a positive urine morphine test, had a higher plasma concentration of cotinine (P = 0.005), but a lower plasma concentration-to-dose ratio of both R- and S-methadone (P = 0.001 and 0.012, respectively) than the responders. OPRM1 genetic variants, rs1074287, rs6912029, rs1799971, rs12209447, rs510769, rs3798676, rs553202, rs7748401, rs495491, rs10457090, rs589046, rs3778152 and rs563649, were significantly associated with the plasma concentration of cotinine when using recessive model for genotypes (general linear model (GLM), P<0.038; false discovery rate (FDR)<0.035) and additive model for allele types (GLM, P<0.03; FDR<0.049) in association analyses. The G allele carriers of SNP rs1799971 (A118G) on exon 1 of OPRM1 gene had a lower plasma cotinine concentration than the A allele carriers (GLM, P = 0.029). OPRM1 genetic polymorphisms are associated with the plasma concentration of cotinine in a Taiwanese MMT cohort. Carriers with the major allele of SNP rs1799971 had a higher plasma cotinine concentration.

Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study.

AIM: To examine comprehensively the relationship between exposure to four classes of psychotropic drugs including antipsychotics, antidepressants, benzodiazepines (BZDs) and Z-drugs, and motor vehicle accidents (MVAs). METHOD: The authors conducted a matched case-control study of 5183 subjects with MVAs and 31 093 matched controls, identified from the claims records of outpatient service visits during the period from 2000 to 2009. Inclusion criteria were defined as subjects aged equal to or more than 18 years and involved in MVAs. Conditional logistic regressions with covariates adjustment (including urbanity, psychiatric and non-psychiatric outpatient visits and Charlson comorbidity score) were applied to examine the effect of four classes of psychotropic drugs on MVAs. RESULTS: Significant increased risk of MVAs was found in subjects taking antidepressants within 1 month (adjusted odds ratio (AOR) 1.73, 95% confidence interval (CI) 1.34, 2.22), 1 week (AOR 1.71, 95% CI 1.29, 2.26), and 1 day (AOR 1.70, 95% CI 1.26, 2.29) before MVAs occurred. Similar results were observed in subjects taking benzodiazepines (BZDs) (AOR 1.56, 95% CI 1.38, 1.75 for 1 month; AOR 1.64, 95% CI 1.43, 1.88 for 1 week, and AOR 1.62, 95% CI 1.39, 1.88 for 1 day) and Z-drugs (AOR 1.42, 95% CI 1.14, 1.76 for 1 month, AOR 1.37, 95% CI 1.06, 1.75 for 1 week, AOR 1.34, 95% CI 1.03, 1.75 for 1 day), but not antipsychotics. Moreover, significant dose effects of antidepressants (equal to or more than 0.6-1.0 DDD), BZDs (equal to or more than 0.1-0.5 DDD) and Z-drugs (more than 1 DDD) were observed, respectively, on the risk of experiencing an MVA. CONCLUSION: Taken together, subjects taking antidepressants, BZDs and Z-drugs, separately, should be particularly cautioned for their increasing risk of MVAs.

ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment.

OBJECTIVE: ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) is a drug transporter protein expressed on the epithelial cells of the intestine and the endothelial cells of the blood-brain barrier. Intestinal ABCB1 actively transports drugs from the cell membrane and prevents them from entering the blood stream whereas the blood-brain barrier ABCB1 prevents drugs from entering the central nervous system. In this study, we tested whether genetic polymorphisms within the ABCB1 gene are associated with the severity of depression and the effectiveness of the antidepressant, escitalopram (S-CIT), in treating major depressive disorder (MDD). METHODS: Twenty single nucleotide polymorphisms in the ABCB1 gene were selected and genotyped in 100 MDD patients who had undergone S-CIT treatment continuously for 8 weeks. The serum concentrations of S-CIT and its metabolites (S-desmethylcitalopram and S-didesmethylcitalopram) were then measured at weeks 2, 4, and 8. RESULTS: The ABCB1 genotypes of rs1922242 (P=0.0028) and rs1202184 (P=0.0021) showed significant association with the severity of depressive symptoms as assessed by the Hamilton Rating Scale for Depression adjusted with Hamilton Rating Scale for Anxiety. The haplotype block, rs1882478-rs2235048-rs2235047-rs1045642-rs6949448 (from intron 27 to intron 26), of ABCB1 was found strongly associated with the remission rate (global P=0.003, d.f.=69) in which haplotype T-T-T-C-C was associated with a slower remission rate on S-CIT treatment (P=0.001). The haplotypes may not be indicators of the severity of depression or anxiety. CONCLUSION: Our findings suggest that single nucleotide polymorphisms in the ABCB1 gene may be indicators of the severity of depression and of the likely S-CIT treatment remission response in MDD.

CYP2B6 polymorphisms influence the plasma concentration and clearance of the methadone S-enantiomer.

Methadone is a racemic compound composed of the R-form and S-form enantiomers. The drug is usually used in maintenance therapy for the heroin-addicted patients. In our previous study, we found that the cytochrome P-450 (CYP) isozyme 2B6 preferentially metabolizes the S-methadone enantiomer. We thus tested whether CYP2B6 gene polymorphisms had any influence on the concentration or clearance of methadone. Ten single nucleotide polymorphisms within this gene region were evaluated in 366 patients undergoing methadone maintenance for at least 3 months. The plasma steady-state levels of racemic methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine were then measured in these individuals. The rs10403955 (T allele in intron 1), rs3745274 (G allele in exon 4), rs2279345 (T allele in intron 5), and rs707265 (A allele in exon 9) CYP2B6 allele types were found to be significantly associated with a higher clearance, a lower plasma concentration, and a lower concentration-to-dosage (C/D) ratio of (S)-methadone (P < 0.0017). Two haplotype blocks of a trinucleotide haplotype (rs8100458-rs10500282-rs10403955 in intron 1) and a hexanucleotide haplotype (rs2279342-rs3745274-rs2279343-rs2279345-rs1038376-rs707265 from intron 2 to exon 9) were constructed within CYP2B6. The major combinations of T-T-T and A-G-A-T-A-A of these particular haplotypes showed significant associations with the plasma concentrations of S-methadone and its C/D ratio (P < 0.0001, respectively). We conclude that genetic polymorphisms in the CYP2B6 gene may therefore be indicators of the clearance, plasma concentration and C/D ratio of S-methadone.

Effect of benzodiazepine discontinuation on dementia risk.

OBJECTIVES: This study aimed to examine whether benzodiazepine (BZD) discontinuation would decrease the risk of dementia. DESIGN: A population-based nested case-control study of dementia was used. SETTING: All subjects aged 45 years or older and enrolled in the National Health Insurance Research Database in Taiwan between 1997 and 2007 were randomly selected. PARTICIPANTS: A total of 8,434 cases had been identified with dementia at least three times in ambulatory claims or with one record in inpatient claims. They were individually matched with two comparison subjects (N = 16,706) by age, gender, and index date. MEASUREMENTS: The lengths of discontinuation, cumulative BZD dose, and potential confounding factors, including medical and psychiatric disorders, were measured and used for further analysis. RESULTS: Compared with nonusers, current users had an increased risk of dementia (adjusted odds ratio [aOR] = 2.71; 95% confidence interval [CI], 2.46-2.99). The dementia risk for former users was reduced as the duration of discontinuation lengthened (<1 month aOR = 2.40, 95% CI, 1.98-2.92; 1-3 months aOR = 1.93, 95% CI, 1.67-2.23; 3-6 months aOR = 1.49, 95% CI, 1.28-1.74; 6-12 months aOR = 1.43, 95% CI, 1.25-1.64; 1-2 years aOR = 1.23, 95% CI, 1.09-1.40; 2-3 years aOR = 1.22, 95% CI, 1.06-1.40; and >3 years aOR = 1.08, 95% CI, 0.98-1.20). The decreasing trend was significant (p < 0.001). CONCLUSION: The risk of dementia was high for current users and decreased as the duration of BZD discontinuation lengthened. Further investigations are needed to replicate this association and explore the underlying mechanism that links long-term BZD use, BZD discontinuation, and the pathogenesis of neurocognitive dysfunction.

Differential relationships of family drinking with alcohol expectancy among urban school children.

BACKGROUND: Positive alcohol outcome expectancy has consistently been linked with problematic drinking, but there is little population-based evidence on its role on early stages of drinking in childhood. The present study seeks to understand the extent to which drinking of family members is differentially associated with the endorsement of alcohol expectancy in late childhood. METHODS: A representative sample of 4th and 6th graders (N = 2455) drawn from 28 public schools in an urban region of Taiwan completed a self-administered paper-and-pencil questionnaire. Each student provided information on alcohol expectancy, drinking experiences, and individual and family attributes. Complex survey analyses were performed to evaluate the relationship, with stratification by children's alcohol drinking history. RESULTS: An estimated 29% of the 4th graders and 43% of the 6th graders had initiated alcohol consumption (over 40% of them had drank on three or more occasions). Alcohol drinking-related differences appear in both the endorsement and the correlates of alcohol expectancy. Positive alcohol expectancy was strongly associated with family drinking, particularly the dimension of "enhanced social behaviors"; negative alcohol expectancy was inversely associated with drinking frequency. Among alcohol naïve children, significant connections appear between paternal drinking and three dimensions of positive alcohol expectancy (i.e., enhanced social behaviors:ßwt = 0.15, promoting relaxation or tension reduction:ßwt = 0.18, and global positive transformation:ßwt = 0.22). CONCLUSIONS: Individual tailored strategies that address family influences on alcohol expectancy may be needed in prevention programs targeting drinking behaviors in children.

Ethnic differences in antidepressant response: a prospective multi-site clinical trial.

BACKGROUND: Although depression is a highly prevalent condition that occurs in all ethnic groups, the influence of ethnicity on treatment response still remains unclear. METHODS: A prospective 8-week, open-label clinical trial comparing the efficacy and side effects of citalopram (CIT) with dose escalation (20-60 mg/day) was performed in African-Americans and Caucasians with nonpsychotic major depression. The intent-to-treat sample consisted of 301 participants (169 African-Americans and 132 Caucasians). RESULTS: Although African-Americans were more socially disadvantaged and had a more severe depression, outcomes between the groups were similar. Remission rates were approximately 50% in both groups and about 2/3 of participants met response criteria. Retention was greater than 75% in both groups, with no differences in dropout rate. There were no differences in the number of completers, number of visits made, final dose of CIT, or in side effect profiles. CONCLUSIONS: These results confirm the growing body of evidence, including recent studies using measurement-based care, that patients from minority groups have outcomes that are similar to those of Caucasians. The provision of measurement-based care and encouragement of patient participation can reduce ethnic differences in response to treatment for depression.

Development of a method to measure methadone enantiomers and its metabolites without enantiomer standard compounds for the plasma of methadone maintenance patients.

A liquid chromatography-photodiode array (LC-PDA) method using a chiral analytical column was developed to determine the plasma levels of enantiomers of methadone and its chiral metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), without the standard compounds of R-form or S-form enantiomers. This method was established by the characteristics of recombinant cytochrome P-450 (CYP) isozymes, where CYP2C19 prefers to metabolize R-methadone and CYP2B6 prefers to metabolize S-methadone. We incubated the racemic methadone standard with either enzyme for 24 h. We identified the retention times of R- and S-methadone to be around 10.72 and 14.46 min, respectively. Furthermore, we determined the retention times of R- and S-EDDP to be approximately 6.76 and 7.72 min, respectively. No interferences were shown through the retention times of morphine, buprenorphine and diazepam. With the high recovery rate of a solid-phase extraction procedure, this method was applied in analyzing plasma concentrations of seven methadone maintenance patients where R- and S-methadone and R- and S-EDDP were 233.4 +/- 154.9 and 185.9 +/- 136.3 ng/mL and 84.4 +/- 99.4 and 37.6 +/- 22.9 ng/mL, respectively. These data suggest that the present method can be applied for routine assay for plasma methadone and EDDP concentrations for patients under treatment.

Increased risks of congenital, neurologic, and endocrine disorders associated with autism in preschool children: cognitive ability differences.

OBJECTIVE: To investigate the increased risk of congenital, neurologic, and endocrine disorders in autistic preschool children and to probe possible cognitive impairment-associated variation in such risks. STUDY DESIGN: Using a population-based longitudinal study, a total of 3440 autistic children born in 1997-1999 and 33,391 age- and residential urbanicity-matched control subjects were identified from the National Health Insurance Research Database in Taiwan. Conditional logistic analyses were performed to estimate the strength of association stratified by the presence of cognitive impairment. RESULTS: Autistic children were found to have greatly elevated risks of congenital anomalies (eg, tuberous sclerosis: adjusted odds ratio [aOR] = 34 approximately 61) and neurologic disorders (eg, epilepsy: aOR = 5 approximately 13) compared with their matched nonautistic peers. The increased risk of medical diseases for mentally retarded autism were approximately 1.6 to 9 times greater than those for isolated autism. CONCLUSIONS: The observed cognitive impairment-related variation in the increased risk of congenital, neurological, and endocrine disorders with autism may provide some clinical and etiologic implications that warrant investigation in the future.

The association between dementia and long-term use of benzodiazepine in the elderly: nested case-control study using claims data.

OBJECTIVES: The aim of this study was to examine the association between long-term benzodiazepines (BZDs) use and the risk of dementia. DESIGN: Population-based nested case-control study of dementia. SETTING: All subjects were aged 45 and older and enrolled in the National Health Insurance Research Database in Taiwan, 1997-2004. PARTICIPANTS: Cases (N = 779) were patients who were identified with dementia at least two times in their outpatient claims. They were individually matched to six comparison subjects (N = 4,626) based on age and gender. MEASUREMENTS: BZD usage (average dosage per year, average days per year, and cumulative dose and periods) and potential confounding comobidities, including cardiovascular and psychiatric diseases. RESULTS: Subjects with dementia had higher cumulative dose, longer duration of BZDs exposure, and more likelihood to be long-term BZDs users. CONCLUSION: Our findings suggest that long-term use of BZDs is associated with an increased risk for dementia, but the underlying mechanisms remain unclear, and further investigations are needed. Long-term use of BZDs should be avoided among the elderly, who may be at a higher risk for developing dementia, in addition to other health problems.

Multidimensional assessments of impulsivity in subjects with history of suicidal attempts.

OBJECTIVE: This study aimed to examine whether subjects with history of suicidal attempts had higher impulsivity as measured by neurocognitive tests and self-report questionnaires. The interrelationships among different impulsivity measures were also explored. METHODS: Fifty-four nonpsychotic psychiatric inpatients, including 24 subjects with previous history of suicidal attempts and 30 comparison subjects without previous suicidal attempts, completed the self-report Barratt Impulsiveness Scale-11-Chinese version (BIS-11-CH) and 2 neuropsychologic tests of impulsivity: the immediate memory task/delayed memory task (IMT/DMT) and the single key impulsivity paradigm (SKIP). RESULTS: The results indicated that subjects with previous suicidal attempts exhibited higher BIS-11-CH factor 2 (lack of self-control/attentional impulsivity) subscore (P = .02) and more commission errors in IMT (P = .03). However, BIS-11-CH scores and performance indices of IMT/DMT and of SKIP did not correlate with each other. CONCLUSIONS: Our findings supported that subjects with previous suicidal attempts had higher impulsivity, which could be revealed by both self-report and neurocognitive measures. However, there is no correlation among self-report, IMT/DMT, and SKIP measures, indicating that they might be measuring different dimensions of impulsivity.

Identity, stigma, and HIV risk among transgender women: a qualitative study in Jiangsu Province, China.

BACKGROUND: Transgender women have multiple disparities globally, including social rejection and stigma, HIV infection and untreated mental health problems. However, few data on transgender women are available in China. Therefore, this study aimed to explore transgender women's experiences on gender identity, disclosure, discrimination, transgender-specific medical care, and perceptions of HIV and sexually transmitted infections (STI) risk in China. METHODS: A qualitative study was conducted in Nanjing and Suzhou city, China in 2018. Key informant interviews (n = 14) and focus group discussions (n = 2) with diverse transgender women were implemented. Text was transcribed and translated, and Dedoose™ software was used for coding, analysis and interpretation by the research team. RESULTS: Chinese transgender women share experiences with transgender women worldwide, including a long and challenging identity search, stigma and discrimination, poor access to trans-specific services and unmet needs for mental health care. Features unique to them include terms used for self-identification, culturally-shaped expectations for reproduction, and ideals of placing the familial and societal welfare over personal fulfillment. Social networks of this population appear sparse, scattered, and underground. Familial rejection was experienced by nearly all respondents. Perceptions of HIV and STI risk and history of HIV testing were notably low. CONCLUSIONS: Transgender women in China face high social rejection and discrimination along with unmet need for various types of healthcare. Scaling up transgender-specific services including gender-affirming medical care, mental health care and HIV/STI prevention are warranted to address the social, medical and mental health of transgender women in China.

Benzodiazepine and risk of hip fractures in older people: a nested case-control study in Taiwan.

OBJECTIVE: To examine the characteristics of benzodiazepines usage and their associations with hip fractures. METHOD: All subjects were aged 65 and older and enrolled in the National Health Insurance program in Taiwan, 2001-2004. Cases (N = 217) were elderly patients who were identified with hip fractures for the first time in their outpatient claims. They were individually matched to 1,214 comparison patients based on age, gender, and index year. Benzodiazepine usage (doses, duration, half-life) and the other covariates including comorbidities, health care utilization, and psychotropic medications used in the 180 days before index events were constructed. RESULTS: Using nonusers as reference group, use of benzodiazepines was significantly associated with hip fractures (adjusted odds ratio [AOR] = 1.7, 95% confidence interval [CI] = 1.2-2.5). Such risks appear to be particularly high during the first month (AOR = 5.6, 95% CI = 2.7-11.8) of exposure, doses higher than 3.0 mg/day in diazepam equivalents (AOR = 1.8, 95% CI = 1.1-3.1), and using short-acting benzodiazepines (AOR = 1.8, 95% CI = 1.3-2.7). CONCLUSIONS: Benzodiazepine exposure in the elderly increases the risk of hip fractures. This is true even with modest dosage, short-acting agents and short-term exposures. Clinicians should prescribe benzodiazepines judiciously with the elderly to minimize drug-related hip fractures.

Urbanicity-related variation in help-seeking and services utilization among preschool-age children with autism in Taiwan.

The present study examines urbanicity-related differences in help-seeking process among preschool children with autism and investigates the factors associated with utilization of autism-related services within the year of diagnosis. Using the 1997-2004 National Health Insurance Research Database (NHIRD) in Taiwan, we identified a total of 3495 autistic children born in 1997-1999 and 13964 matched controls. Results indicate that suburban and rural autism tended to receive the diagnosis at an older age and to have a longer diagnosis process as compared with urban counterparts. Male gender, a younger age of diagnosis, and being diagnosed by psychiatric specialty strongly predict subsequent greater utilization of autism-specific services (all p < 0.05). Health policy makers and other service providers should address the needs of children with early-onset neurodevelopmental disorders in rural areas, particularly those from disadvantaged families.

Pharmacogenomic strategy for individualizing antidepressant therapy.

Despite remarkable progress, pharmacotherapy in general, including that for the treatment of depressive conditions, has often ignored the magnitude and clinical significance of the huge interindividual variations in pharmacokinetics and pharmacodynamics, resulting in poor compliance, suboptimal therapeutic effects, and treatment resistance. Advances in pharmacogenomics and computer modeling technologies hold promise for achieving the goals of "individualized" ("personalized") medicine. However, the challenges for realizing such goals remain substantial. These include the packaging and interpretation of genotyping results, changes in medical practice (innovation diffusion), and infrastructural, financing, ethical, and organizational issues related to the use of new information.

Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic comparative study.

OBJECTIVES: Our objectives were to investigate cytochrome P450 (CYP) 2C19 polymorphism in Mexican Americans and compare the findings with those in 4 other ethnic groups. METHODS: The CYP2C19 genotype (n = 346) and S-mephenytoin hydroxylation phenotype (n = 220) were studied in a Mexican American population from Los Angeles County. Another 4 ethnic groups, African Americans (n = 236), whites (n = 273), East Asians (n = 161), and Southeast Asians (n = 80), were also recruited from Los Angeles County and genotyped and phenotyped for CYP2C19. RESULTS: The frequencies of CYP2C19*2 and *3 were 9.7% and 0.1%, respectively, in Mexican Americans, which were lower than those of the other 4 ethnic groups, ranging from 12.7% to 31.2% and 0.8% to 9.6%, respectively (P

Effect of bupropion on nocturnal urinary free cortisol and its association with antidepressant response.

The study examined the relationship between pre-treatment nocturnal hypothalamic-pituitary-adrenal (HPA) activity, as reflected by nocturnal urinary free cortisol (NUFC) response to a single-dose of sustained-release bupropion, and the antidepressant effect of the drug. NUFC changes in response to treatment with bupropion also were assessed. NUFC was measured in 20 patients with unipolar major depressive disorder before and after initiating treatment with sustained-release bupropion. Prior to treatment, subjects were studied on two separate sessions, one week apart. On the morning of each session, the participants received bupropion (150 mg, PO) or placebo using a randomized, double-blind procedure. Following the second session, subjects then received open-label treatment with bupropion for 8 weeks. NUFC sampling was repeated at the end of treatment. There was a significant interaction between NUFC concentration in response to single-dose bupropion and its antidepressant effect. Treatment non-responders showed a significant increase in NUFC in response to a single-dose of bupropion, whereas responders showed no such change. In addition, the NUFC response to bupropion challenge correlated significantly with the change in depression ratings as a result of treatment. In contrast to many other antidepressants, treatment with bupropion for 8 weeks did not reduce HPA activity in either responders or non-responders. These findings suggest that the NUFC response to a test-dose of bupropion might be helpful in predicting its antidepressant effect. One possible mechanism for the association between the NUFC response to acute bupropion challenge and antidepressant efficacy might be linked through dopaminergic and/or noradrenergic mechanisms.

Effects of genetic variants of ADH1B and ALDH2 and social network on continued alcohol drinking among young adolescents in Taiwan.

BACKGROUND: This study aimed (i) to evaluate the effects of genetic variants of ADH1B and ALDH2 and social network position on continued alcohol use in early adolescence, and (ii) to explore possible moderating role of pubertal development on genetic effects. METHODS: The sample comprised 496 children who ever drank alcohol before the ages of 10-12. Information pertaining to sociodemographic background, pubertal development, parental drinking, alcohol and tobacco use, alcohol-metabolizing genes, and nominated best friends was collected in four waves of assessment. Polymorphisms of ADH1B (rs1229984) and ALDH2 (rs671) were genotyped. The latent class analysis was first used to characterize longitudinal alcohol use pattern, followed by the multinomial logistic regression analyses to assess its association with genes, pubertal development, and social network. RESULTS: Three distinct classes of alcohol users (i.e. ex-drinkers, sporadic drinkers, and continued drinkers) were derived from alcohol-experienced children. Both alcohol-metabolizing genes appear to have protective effects, yet such relationships were only significant for youngsters in pre-to-early pubertal stage: the adjusted odds ratio (aOR) of ADH1B fast-genotype for sporadic drinkers was 0.46 and that of ALDH2 slow-genotype for both sporadic and continued drinkers was 0.47 and 0.42, respectively. Children having the bridge position in their peer network were more likely to be sporadic drinkers (aOR=4.15) and continued drinkers (aOR=3.16). CONCLUSIONS: Our results illustrate a potential moderating effect of pubertal development on the protective influence of alcohol-metabolizing genes on subsequent alcohol use among alcohol-experienced children as well as the independent contribution of early life's social network to their alcohol involvement.