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Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84–2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%–8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| < 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42–0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Introduction and aims: Illicit methamphetamine (MA) use is an important public health concern. There is a dearth of knowledge about effective and cost-effective treatments for methamphetamine (MA) dependence in Australia. This article evaluates the cost-effectiveness of counselling as a treatment option for illicit MA use compared with no treatment option. Design and methods: Data are from 501 individuals recruited into Methamphetamine Treatment Evaluation Study (MATES). The population of MA users from MATES is extrapolated to a total number of 1000 MA users in the intervention group (counselling treatment) and control group (non-treatment group). A decision analytic model is developed that examines the costs and health outcomes [measures as quality adjusted life years (QALYs) gained] for the treatment and comparison group over a 3-year period. A societal perspective is adopted and model inputs are subject to sensitivity and uncertainty analysis to test the robustness of results to parameter variability. Results are discounted by using 3% discount rate and expressed in 2011 Australian dollars. Results: The incremental cost-effectiveness analysis suggests that counselling is a dominant health care intervention, i.e. saves money and is more effective than a do nothing intervention. The incremental difference in costs is -AU$18.36 million (95% CI -AU$22.80 million to -AU$14.31 million) and the incremental difference in QALY is 107 (95% CI -640 to 820) with a probability of 78.64% of counselling being a dominant and cost-effective treatment within the acceptable incremental cost-effectiveness ratio (ICER) of $63832 per QALY in the Australian society. The results of the sensitivity analysis show that the ICER is most sensitive to change in five major inputs: baseline utility, utility at 3 months, dealing crime costs, property crime costs and fraud crime costs. Discussion and Conclusions: The economic evaluation of the cost-effectiveness of counselling for MA dependence

Aims: To determine whether violent behaviour increases during periods of methamphetamine use and whether this is due to methamphetamine-induced psychotic symptoms. Design: A fixed-effects (within-subject) analysis of four non-contiguous 1-month observation periods from a longitudinal prospective cohort study. Setting: Sydney and Brisbane, Australia. Participants: A total of 278 participants aged 16 years or older who met DSM-IV criteria for methamphetamine dependence on entry to the study but who did not meet DSM-IV criteria for life-time schizophrenia or mania. Measurements: Violent behaviour was defined as severe hostility in the past month on the Brief Psychiatric Rating Scale (BPRS) (corresponding to assault/damage to property). Days of methamphetamine and other substance use in the past month were assessed using the Opiate Treatment Index. Positive psychotic symptoms in the past month were identified using the BPRS. Findings: There was a dose-related increase in violent behaviour when an individual was using methamphetamine compared with when they were not after adjusting for other substance use and socio-demographics [cf. no use in the past month: 1-15 days of use odds ratio (OR)=2.8, 95% confidence interval (CI)=1.6-4.9; 16+ days of use OR=9.5, 95% CI=4.8-19.1]. The odds of violent behaviour were further increased by psychotic symptoms (OR=2.0, 95% CI=1.1-3.6), which accounted for 22-30% of violent behaviour related to methamphetamine use. Heavy alcohol consumption also increased the risk of violent behaviour (OR=3.1, 95% CI=1.4-7.0) and accounted for 12-18% of the violence risk related to methamphetamine use. Conclusions: There is a dose-related increase in violent behaviour during periods of methamphetamine use that is largely independent of the violence risk associated with psychotic symptoms.

Little is known about the effectiveness of available treatment options for methamphetamine (MA) abuse and dependence. This study aimed to measure improvements in health-related quality of life (HRQL) among MA users associated with different treatment opti

Objective: To determine whether mothers who quit or reduce their level of smoking in pregnancy comprise a group of health-conscious women who are disproportionally likely to adopt a healthier smoking lifestyle in the medium to longer term, compared with women who continue to smoke during pregnancy. Design: A prospective cohort study. Setting: A public hospital in Australia. Population: A cohort of 6703 individual mothers who completed both initial phases of data collection in 1981-1983; mothers who smoked daily (2992) before pregnancy were included in this study. Methods: Mothers were interviewed at 3-5 days post-delivery, 6 months, 5 years, 14 years and 21 years to determine their smoking status. An inverse probability-weighted Poisson regression with a robust error variance was fitted to the data using a log-link function and a binary response variable for smoking outcome, and adjusting for several possible confounding factors. Main outcome measure: Smoking cessation at several follow-up points, for up to 21 years. Results: Of the mothers who smoked daily before pregnancy, 12, 23, 37 and 41% reported having ceased smoking at 6 months and at 5, 14 and 21 years, respectively. The decision to quit smoking during pregnancy was found to be independently associated with a higher rate ratio (RR) of smoking cessation at 6 months (RR 30.60, 95% CI 20.50-45.69), 5 years (RR 4.36; 95% CI 3.61-5.27), 14 years (RR 2.42, 95% CI 2.12-2.75) and 21 years (RR 1.86; 95% CI 1.60-2.15), after adjusting for several possible confounding factors. Conclusions: Pregnancy appears to be an opportunity for successfully quitting smoking, regardless of socio-economic circumstances or demographic background.

Methamphetamine (MA) is a public health problem both in Australia and internationally and very little is known about the most cost-effective treatment options. This study is a review of recent studies and an assessment of current treatment options for MA

Aims: To evaluate the impact of community-based drug treatment on methamphetamine use using inverse probability of treatment-weighted (IPTW) estimators to derive treatment effects. Design: A longitudinal prospective cohort study with follow-ups at 3 months, 1 year and 3 years. Treatment effects were derived by comparing groups at follow-up. IPTW estimators were used to adjust for pre-treatment differences between groups. Setting: Sydney and Brisbane, Australia. Participants: Participants were methamphetamine users entering community-based detoxification (n=112) or residential rehabilitation (n=248) services and a quasi-control group of methamphetamine users (n=101) recruited from the community. Measurements: Frequency of methamphetamine use between interviews (no use, less than weekly, 1-2 days per week, 3+ days per week), continuous abstinence from methamphetamine use, past month methamphetamine use and methamphetamine dependence. Findings: Detoxification did not reduce methamphetamine use at any follow-up relative to the quasi-control group. Relative to quasi-control and detoxification groups combined, residential rehabilitation produced large reductions in the frequency of methamphetamine use at 3 months [odds ratio (OR)=0.23, 95% confidence interval (CI) 0.15-0.36, P<0.001), with a marked attenuation of this effect at 1 year (OR 0.62, 95% CI 0.40-0.97, P=0.038) and 3 years (OR=0.71, 95% CI 0.42-1.19, P=0.189). The greatest impact was for abstinence: for every 100 residential rehabilitation clients there was a gain of 33 being continuously abstinent at 3 months, with this falling to 14 at 1 year and 6 at 3 years. Conclusions: Community-based residential rehabilitation may produce a time-limited decrease in methamphetamine use, while detoxification alone does not appear to do so.