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Background: The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues. Here, we aim to identify blood DNAm differences associated with PTSD and characterize the underlying biological mechanisms by examining the extent to which they mirror associations across multiple brain regions., Methods: As the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, we conducted the largest cross-sectional meta-analysis of epigenome-wide association studies (EWASs) of PTSD to date, involving 5077 participants (2156 PTSD cases and 2921 trauma-exposed controls) from 23 civilian and military studies. PTSD diagnosis assessments were harmonized following the standardized guidelines established by the PGC-PTSD Workgroup. DNAm was assayed from blood using either Illumina HumanMethylation450 or MethylationEPIC (850K) BeadChips. A common QC pipeline was applied. Within each cohort, DNA methylation was regressed on PTSD, sex (if applicable), age, blood cell proportions, and ancestry. An inverse variance-weighted meta-analysis was performed. We conducted replication analyses in tissue from multiple brain regions, neuronal nuclei, and a cellular model of prolonged stress., Results: We identified 11 CpG sites associated with PTSD in the overall meta-analysis (1.44e-09 < p < 5.30e-08), as well as 14 associated in analyses of specific strata (military vs civilian cohort, sex, and ancestry), including CpGs in AHRR and CDC42BPB . Many of these loci exhibit blood-brain correlation in methylation levels and cross-tissue associations with PTSD in multiple brain regions. Methylation at most CpGs correlated with their annotated gene expression levels., Conclusions: This study identifies 11 PTSD-associated CpGs, also leverages data from postmortem brain samples, GWAS, and genome-wide expression data to interpret the biology underlying these associations and prioritize genes whose regulation differs in those with PTSD., Competing Interests: Competing interests CYC is an employee of Biogen. NPD has served on scientific advisory boards for BioVie Pharma, Circular Genomics and Sentio Solutions for unrelated work. NRN serves as an unpaid member of the Ilumivu advisory board. SAMR receives support from the Wounded Warrior Project (WWP), Department of Veterans Affairs (VA), National Institute of Health (NIH), McCormick Foundation, Tonix Pharmaceuticals, Woodruff Foundation, and Department of Defense (DOD). Dr. Rauch receives royalties from Oxford University Press and American. KJR serves as a consultant for Acer, Bionomics, and Jazz Pharma; SABs for Sage, Boehringer Ingelheim, and Senseye. DJS has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda and Vistagen. MBS has in the past 3 years received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, BigHealth, Biogen, Bionomics, BioXcel Therapeutics, Boehringer Ingelheim, Clexio, Delix Therapeutics, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, PureTech Health, Sage Therapeutics, Sumitomo Pharma, and Roche/Genentech. MBS has stock options in Oxeia Biopharmaceuticals and EpiVario. MBS has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). MBS has also received research support from NIH, Department of Veterans Affairs, and the Department of Defense. MBS is on the scientific advisory board for the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Vietnamese medical students believe becoming "strong" drinkers is important for their future career working as doctor. However, it is unclear if this is a temporary behaviour associated with life as a student, or a phenomenon associated with the transition to working as a medical practitioner., Objective: This study explored changes in alcohol-related perceptions and behaviour among Vietnamese early career doctors working after graduation., Methods: In-depth interviews were conducted with 15 Vietnamese early career doctors in Hanoi city. Thematic analysis was used to analyse the qualitative data., Results: Vietnamese early career doctors perceived binge drinking as common among doctors, especially male doctors, surgeons, and preventive medicine doctors. This perception was different from when they were medical students because, at that time, they believed doctors would not drink alcohol at hazardous levels. Additionally, Vietnamese early career doctors' drinking behaviour changed in the frequency and quantity of alcohol consumption after graduation due to peer pressure, job stress, working collaborations, and working environment., Conclusions: Vietnamese early career doctors changed their alcohol-related perceptions and behaviour after graduation. Gender, mental health (stress), factors related to the working environment, and the role of professional relationships should be considered in strategies to reduce risky alcohol consumption among Vietnamese early career doctors.

Background: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs)., Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms., Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program., Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods., (Copyright © 2021 Society of Biological Psychiatry. All rights reserved.)

Background and Aims: Negative affect and alcohol craving are common features of Alcohol Use Disorder (AUD). Both independently contribute to AUD severity and poorer treatment outcomes, but their relationship is poorly understood. Multidimensional alcohol craving measures now allow for examination of key dimensions of craving. This study explored the relationship between depression, anxiety, stress, and the alcohol craving dimensions of intensity, imagery and intrusiveness., Method: Five-hundred and twenty-five treatment seeking AUD patients (mean age of 39.79 years, SD = 11.57 years, 67% male) completed the Depression Anxiety Stress Scales (DASS), Alcohol Use Disorder Identification Test-Consumption items (AUDIT-C), and Alcohol Craving Experience (ACE-F) questionnaire, which measured the frequency of craving intensity, imagery and intrusiveness. Regression models predicted main effects of predictors and moderation by alcohol consumption., Results: Higher levels of stress were independently associated with increased craving intensity, imagery and intrusiveness. Significant positive associations were also found between anxiety and craving imagery. The association between depression and craving was not significant after controlling for other predictors., Conclusions: AUD patients experienced higher cravings when stressed and greater imagery when anxious. These results support the need to consider the relationships between stress and craving when managing alcohol dependence., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Self-efficacy is a core component of Social Cognitive Theory. Refusal self-efficacy is an individual's belief in their ability to refuse a substance in specific high-risk situations. Change in refusal self-efficacy is predictive of positive treatment outcomes. Measurement of refusal self-efficacy is critical as it directs coping skills development techniques though existing behavioural treatments. There is no validated measure of stimulant refusal self-efficacy. This study developed and validated the Stimulant Refusal Self-Efficacy Questionnaire (SRSEQ) to measure confidence in the ability to refuse stimulants in specific high-risk situations., Method: Two hundred and seven stimulant-using patients referred for assessment completed the SRSEQ and measures including stimulant dependence severity (Severity of Dependence Scale-Stimulant, SDS-S). Confirmatory Factor Analysis (CFA) using structural equation modelling (SEM) was conducted to test the theoretically-driven three-factor structure of the SRSEQ. Criterion validity was tested with severity of stimulant dependence., Results: The CFA supported the three-factor structure. Emotional Relief (β = -0.27, p = .008), Opportunistic (β = -0.24, p = .013) and Social Facilitation (β = -0.32, p < .001) refusal self-efficacy were uniquely associated with stimulant dependence severity, explaining 55.1% variance., Conclusions: The SRSEQ is psychometrically sound and may be clinically useful to assist with assessment and treatment planning for stimulant use disorder., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Alcohol is a commonly used substance among Vietnamese medical students, especially males. Vietnamese male medical students drink more alcohol, report more intentions to binge drink, and experience more alcohol-related problems than females. As medical students' alcohol consumption may influence their attitudes and medical practice relating to alcohol counseling and prevention, research about the cultural and drinking norms underlying the drinking behavior of Vietnamese male medical students is warranted. This study aims to explore the norms underlying drinking behavior of Vietnamese male medical students. A qualitative study including 32 in-depth interviews with Vietnamese male medical students at a medical university. Thematic analysis was used to analyze the data. This study found Vietnamese male medical students considered alcohol consumption as a way to show their masculinity and become accepted by groups. Given these beliefs and adherence to norms, they followed rules to force others to consume more alcohol or be intoxicated in drinking occasions among medical students. This study showed the importance of gender and group norms in influencing Vietnamese male medical students' alcohol consumption. These norms should be considered in future research and interventions addressing alcohol use among this target population.

Background: Methamphetamine has been consistently associated with positive psychotic symptoms, but little is known about whether the reverse also occurs., Aims: This study determined whether the relationship between methamphetamine use and positive psychotic symptoms is bidirectional over 12 months. The impact of lifetime psychotic disorders and methamphetamine dependence on these relationships was also examined., Method: A total of 201 regular (at least monthly) primary methamphetamine users were recruited from free needle and syringe programmes in three Australian cities. Data on the frequency of methamphetamine and other drug use (from Timeline Followback inteviews) and the severity of positive psychotic symptoms (using the Brief Psychiatric Rating Scale) in the past 2 weeks were collected in 12 contiguous monthly face-to-face interviews (mean of 9.14/11 (s.d. = 3.16) follow-ups completed). Diagnoses were derived using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders., Results: The mean age of participants was 31.71 years (s.d. = 8.19) and 39% (n = 77) were women. At baseline 55% (n = 110) were dependent on methamphetamine and 51% (n = 102) had a lifetime psychotic disorder. Cross-lagged dynamic panel models found a significant bidirectional relationship between psychotic symptoms and methamphetamine use (Comparative Fit Index (CFI) = 0.94, standardised root mean square residual (SRMR) = 0.05, root mean square error of approximation (RMSEA) = 0.05, 95% CI 0.04-0.06). The magnitude of the relationship in each direction was similar, and the presence of methamphetamine dependence or a lifetime psychotic disorder did not have an impact on results., Conclusions: A dynamic, bidirectional relationship between methamphetamine and psychotic symptoms of similar magnitude in each direction was found over 1 year. This suggests integrated treatments that target methamphetamine, psychotic symptoms and their interrelationship may be of most benefit.

Globally, cannabis is the most frequently used controlled substance after alcohol and tobacco. Rates of cannabis use are steadily increasing in many countries and there is emerging evidence that there is likely to be greater risk due to increased concentrations of delta-9-tetrahydrocannabinol (THC). Cannabis use and Cannabis Use Disorder (CUD) has been linked to a wide range of adverse health outcomes. Several biological, psychological, and social risk factors are potential targets for effective evidence-based treatments for CUD. There are no effective medications for CUD and psychological interventions are the main form of treatment. Psychological treatments based on Social Cognitive Theory (SCT) emphasize the importance of targeting 2 keys psychological mechanisms: drug outcome expectancies and low drug refusal self-efficacy. This mini-review summarizes the evidence on the role of these mechanisms in the initiation, maintenance, and cessation of cannabis use. It also reviews recent evidence showing how these psychological mechanisms are affected by social and biologically-based risk factors. A new bioSocial Cognitive Theory (bSCT) is outlined that integrates these findings and implications for psychological cannabis interventions are discussed. Preliminary evidence supports the application of bSCT to improve intervention outcomes through better targeted treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gullo, Papinczak, Feeney, Young and Connor.)

Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European ( n = 70,870) and African ( n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study - United Kingdom Biobank - PTSD symptoms were negatively associated with SBP levels (β = -1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sumner, Maihofer, Michopoulos, Rothbaum, Almli, Andreassen, Ashley-Koch, Baker, Beckham, Bradley, Breen, Coleman, Dale, Dennis, Feeny, Franz, Garrett, Gillespie, Guffanti, Hauser, Hemmings, Jovanovic, Kimbrel, Kremen, Lawford, Logue, Lori, Lyons, Maples-Keller, Mavissakalian, McGlinchey, Mehta, Mellor, Milberg, Miller, Morris, Panizzon, Ressler, Risbrough, Rothbaum, Roy-Byrne, Seedat, Smith, Stevens, van den Heuvel, Voisey, Young, Zoellner, PGC-PTSD Physical Health Working Group, Nievergelt and Wolf.)

Background and Aims: Recent meta-analyses of motivational interviewing (MI) for reducing risky alcohol use in young people have reported modest effects. Few studies have targeted individual patient factors to increase MI effectiveness. This study determined if MI enhanced with individualised personality-specific coping skills training (QuikFix) was more efficacious than standard MI or an assessment feedback/information (AF/I) control among young people with alcohol-related injuries or illnesses., Design and Setting: Single-centre, single-blind, three-group superiority randomized controlled trial with 1-, 3-, 6- and 12-months follow-ups. Telephone intervention, Brisbane, Australia., Participants: A total of 398 young people (16-25 years; M age = 20.30 years, SD = 2.12; 54% female) with alcohol-related injuries and/or illnesses were recruited from an emergency department (ED) or rest/recovery service (RRS)., Measures: The primary outcome was total standard (10 g ethanol) drinks in the past month (Timeline Follow back [TLFB]) at 12 months (primary time point). Secondary outcomes were total drinking days and standard drinks per drinking day (TLFB) in the past month and the frequency of alcohol-related problems in the past 3 months (Rutgers Alcohol Problem Index)., Interventions: Young people were randomized to two sessions of QuikFix enhanced with individualised personality-specific coping skills training (n = 132), two sessions of MI (n = 136) or one session of AF/I (n = 130), all delivered by telehealth., Findings: QuikFix resulted in greater reductions (all P < 0.0017) in the primary outcome of total standard drinks (M = 19.50, CI 99.75% = [11.31, 27.68]) than both MI (M = 32.61, CI 99.75% = [24.82, 40.40]; Cohen's D = 0.40) and AF/I (M = 34.12, CI 99.75% = [26.59, 41.65]; D = 0.45) at 12 months (retention n = 324/398, 81%). QuikFix had greater reductions on drinking days (M = 3.16, CI 99.75% = [2.37, 3.96]) than both MI (M = 4.53, CI 99.75% = [3.57, 5.48];D = 0.38) and AF/I (M = 4.69, CI 99.75% = [3.73, 5.65];D = 0.42) and fewer drinks per drinking day (M = 5.02, CI 99.75% = [3.71, 6.33]) than AF/I (M = 7.15, CI 99.75% = [5.93, 8.38;D = 0.47) at 12 months., Conclusions: Young people with alcohol-related injuries and/or illnesses who attended ED and rest/recovery services and received an individualised personality-specific coping skills training intervention (QuikFix) had greater reductions in the amount of alcohol consumed at 12 months compared with those who received motivational interviewing or an assessment feedback/information intervention., (© 2020 Society for the Study of Addiction.)

Background and Aims: Clinical staff are typically poor at predicting alcohol dependence treatment outcomes. Machine learning (ML) offers the potential to model complex clinical data more effectively. This study tested the predictive accuracy of ML algorithms demonstrated to be effective in predicting alcohol dependence outcomes, compared with clinical judgement and traditional linear regression., Design: Prospective study. ML models were trained on 1016 previously treated patients (training-set) who attended a hospital-based alcohol and drug clinic. ML models (n = 27), clinical psychologists (n = 10) and a 'traditional' logistic regression model (n = 1) predicted treatment outcome during the initial treatment session of an alcohol dependence programme., Setting: A 12-week cognitive behavioural therapy (CBT)-based abstinence programme for alcohol dependence in a hospital-based alcohol and drug clinic in Australia., Participants: Prospective predictions were made for 220 new patients (test-set; 70.91% male, mean age = 35.78 years, standard deviation = 9.19). Sixty-nine (31.36%) patients successfully completed treatment., Measurements: Treatment success was the primary outcome variable. The cross-validated training-set accuracy of ML models was used to determine optimal parameters for selecting models for prospective prediction. Accuracy, sensitivity, specificity, area under the receiver operator curve (AUC), Brier score and calibration curves were calculated and compared across predictions., Findings: The mean aggregate accuracy of the ML models (63.06%) was higher than the mean accuracy of psychologist predictions (56.36%). The most accurate ML model achieved 70% accuracy, as did logistic regression. Both were more accurate than psychologists (P < 0.05) and had superior calibration. The high specificity for the selected ML (79%) and logistic regression (90%) meant they were significantly (P < 0.001) more effective than psychologists (50%) at correctly identifying patients whose treatment was unsuccessful. For ML and logistic regression, high specificity came at the expense of sensitivity (26 and 31%, respectively), resulting in poor prediction of successful patients., Conclusions: Machine learning models and logistic regression appear to be more accurate than psychologists at predicting treatment outcomes in an abstinence programme for alcohol dependence, but sensitivity is low., (© 2020 Society for the Study of Addiction.)

Alexithymia is a vulnerability factor for physical and mental illness that can significantly influence the daily function of alcohol-dependent patients. The aim of this study was to examine the indirect effect of obsessive thoughts and compulsive behaviors involving alcohol craving on the relationship between alexithymia, quality of life (QoL) of psychological well-being and health status. Three hundred and eighty-one outpatients (263 males and 118 females) in treatment for alcohol dependence completed self-report measures of alexithymia, alcohol craving, GHQ-28 (QoL-psychological well-being) and SF-36 (QoL-health status). Males scored significantly higher than females on aspects of alexithymia, and females reported significantly higher levels of alcohol craving. Path analysis showed an indirect effect of alcohol craving on the relationship between alexithymia, QoL-psychological well-being and self-reported QoL-health status for males only. The current study provides important new information about impaired self-reported health status and well-being among male alcohol-dependent treatment seekers with alexithymia.

Issue Addressed: Stimulant use has been identified as a key risk factor for sexual behaviours leading to HIV transmission. Substance-related expectancies are associated with substance use and postsubstance use thoughts, feelings and behaviours. Expectancies held by specific cultural subgroups have rarely been investigated, particularly regarding a range of commonly used stimulants., Method: The Stimulant Expectancy Questionnaire for Men who have Sex with Men (SEQ-MSM) was initially generated through consumer panel and interviews regarding the most commonly used stimulants among MSM in Australia (methamphetamine, amphetamines and ecstasy), with initial administration among 98 MSM to facilitate item reduction. A community sample of 427 MSM was used to validate the SEQ-MSM, with exploratory factor analysis (EFA; n = 202) and confirmatory factor analysis (CFA; n = 225)., Results: EFA revealed three distinct substance reinforcement domains ('Enhanced sexual experience', 'Sexual communication and negotiation' and 'Cognitive impairment'). The scale was associated with stimulant consumption patterns (including greater expectancies regarding sexual enhancement among methamphetamine users), and the factor structure, comprising a final form of the MSM-SEQ, was confirmed through CFA., Conclusions: The SEQ-MSM represents a reliable measure of outcome expectancies related to the range of commonly used stimulants among Australian MSM. Development of applied validation studies with the SEQ-MSM is a key next step in advancing health promotion, clinical interventions and research efforts to reduce harm (eg, HIV transmission) associated with stimulant use (particularly methamphetamine) among MSM. SO WHAT?: Objectives: This research maps expectancies specific among gay and men who have sex with men (MSM), and relationships between expectancies and stimulant use patterns and behaviours postuse - including sexual activity (eg, condomless anal sex)., (© 2019 Australian Health Promotion Association.)

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

In this study we investigated genome-wide sperm DNA methylation patterns in trauma-exposed Vietnam veterans. At the genome-wide level, we identified 3 CpG sites associated with PTSD in sperm including two intergenic and one CpG within the CCDC88C gene. Of those associated with PTSD in sperm at a nominal level, 1868 CpGs were also associated with PTSD in peripheral blood (5.6% overlap) including the RORA, CRHR1 and DOCK2 genes that have been previously implicated in PTSD. A total of 10 CpG sites were significantly associated with a reported history of a diagnosed mental health condition in children and reached genome-wide significance. CpGs associated with a history of a reported mental health condition in children were also enriched (90% of tested genes) for genes previously reported to be resistant to demethylation, making them strong candidates for transgenerational inheritance. In conclusion, our findings identify a unique sperm-specific DNA methylation pattern that is associated with PTSD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Alcohol use is common among Vietnamese students. Previous qualitative findings showed Vietnamese medical students believed they were not binge drinkers while reporting many binge drinking occasions they participated in or witnessed. This dichotomy warrants examination. This study aims to establish drinking patterns and examine the factors underlying Vietnamese medical students' binge drinking intention and behaviour. This study used a prospective-correlational design, with two waves of data collection, drawing from established health behaviour models. At Time 1, 206 students completed the Alcohol Use Disorder Identification Test, the standard Theory of Planned Behaviour measures (attitude, subjective norm and perceived behavioural control) and their underlying beliefs, as well as group norm, role identity, drinking culture and past binge drinking behaviour. At Time 2, 156 medical students reported their binge drinking behaviour 2 weeks later. Only 6.8% of participants were classified as problematic drinkers and few participants reported binge drinking occasions at the 2-week follow-up. Perceived behavioural control, friends' group norms, role identity as future doctors, and past behaviour significantly predicted binge drinking intentions and key beliefs were identified. This study indicated Vietnamese medical students' limited engagement with binge drinking and identified key factors to address for those with risky drinking behaviour intentions., (� The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Brain-derived neurotrophic factor (BDNF) gene is associated with increased risk of posttraumatic stress disorder (PTSD) and plays a role in neuroplasticity, cognition and memory. BDNF has strong potential as a therapeutic target as studies have shown that antidepressants, electroconvulsive treatment and exercise modulate BDNF expression and methylation. In this study we examined the role of BDNF methylation and expression in PTSD and the implications of exercise in mediating these effects. BDNF DNA methylation and gene expression analysis was performed in a sample of 96 male Vietnam veterans. Cases were combat-exposed veterans with current PTSD (n = 48) and controls were combat exposed veterans with no past or current PTSD diagnosis (n = 48). No association between BDNF mRNA and PTSD was identified. PTSD was associated with decreased methylation at three BDNF CpG sites (cg01546433 P = 0.004835; cg24650785 P = 0.000259 and cg002298481 P = 0.000672). Differential BDNF methylation was associated with exercise, with active exercise associated with lower methylation levels at three CpG sites (cg04481212 P = 0.005; cg01546433 P = 0.025 and cg00298481 P = 0.035). Given that exercise mediates BDNF action on cognitive plasticity, exercise may be a non-invasive, drug free option in the treatment of PTSD., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Clinical staff providing addiction treatment predict patient outcome poorly. Prognoses based on linear statistics are rarely replicated. Addiction is a complex non-linear behavior. Incorporating non-linear models, Machine Learning (ML) has successfully predicted treatment outcome when applied in other areas of medicine. Using identical assessment data across the two groups, this study compares the accuracy of ML models versus clinical staff to predict alcohol dependence treatment outcome in behavior therapy using patient data only., Methods: Machine learning models (n = 28) were constructed ('trained') using demographic and psychometric assessment data from 780 previously treated patients who had undertaken a 12 week, abstinence-based Cognitive Behavioral Therapy program for alcohol dependence. Independent predictions applying assessment data for an additional 50 consecutive patients were obtained from 10 experienced addiction therapists and the 28 trained ML models. The predictive accuracy of the ML models and the addiction therapists was then compared with further investigation of the 10 best models selected by cross-validated accuracy on the training-set. Variables selected as important for prediction by staff and the most accurate ML model were examined., Results: The most accurate ML model (Fuzzy Unordered Rule Induction Algorithm, 74%) was significantly more accurate than the four least accurate clinical staff (51%-40%). However, the robustness of this finding may be limited by the moderate area under the receiver operator curve (AUC = 0.49). There was no significant difference in mean aggregate predictive accuracy between 10 clinical staff (56.1%) and the 28 best models (58.57%). Addiction therapists favoured demographic and consumption variables compared with the ML model using more questionnaire subscales., Conclusions: The majority of staff and ML models were not more accurate than suggested by chance. However, the best performing prediction models may provide useful adjunctive information to standard clinically available prognostic data to more effectively target treatment approaches in clinical settings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Sun safety is crucial for preventing skin cancer. This study evaluated a school-based intervention based on the theory of planned behaviour (TPB), which aimed to encourage sun-protective behaviour among adolescents., Methods: Secondary school students (N = 382; 61.1% female; M age  = 13.73 y) in Queensland, Australia, participated in the study. Schools were randomly allocated to an intervention or control group. The intervention focussed on fostering positive attitudes, increasing perceptions of normative support, and strengthening control perceptions. Participants completed questionnaires assessing the TPB variables and sun-protective behaviour (weekday and weekend) 1 week before intervention (time 1), 1 week after intervention (time 2), and 4 weeks after intervention (time 3)., Results: With baseline between-group differences in TPB variables matched, repeated-measures multivariate analysis of variance was used to evaluate the Time × Condition effects across time. Multigroup comparisons using path models traced the intervariable changes. From times 1 to 3, a significant improvement in weekend sun-protective behaviour was identified in the intervention group (but not the control group), whereas cognitions showed no significant changes across time for either conditions. Multigroup comparisons on path coefficients between the intervention and control group participants indicated that the intervention group members formed stronger positive associations between perceived behavioural control and intention at time 2 and between perceived control and behaviour at time 3., Conclusion: The significant behavioural change on weekends highlights the value of targeting control perceptions, which may encourage adolescents' sun-protective behaviour. Further studies are needed to understand the absence of significant changes in weekday sun-safe behaviour among this at-risk cohort., (© 2018 John Wiley & Sons, Ltd.)

Background: China is the world's largest tobacco consumer. Smoking initiation dramatically increases from teenage to adulthood. In this study, we investigated adolescents' future smoking intention at critical ages and its associated predictors., Methods: Using a longitudinal design (3 waves) across 6 months in 2016, data from 156 10th graders in two high schools in China were examined. We used latent class growth modelling to explore the heterogeneous trajectories of smoking intentions for two future age groups. Logistic regression was then used to estimate the predictors of trajectories., Results: Two trajectories and three trajectories were identified for future smoking intention in their twenties and forties, respectively. Gender, current smoking status, and mothers' and friends' smoking status all played distinct roles in future smoking intentions., Conclusions: Chinese adolescents' future intentions at critical ages are of concern. Future tobacco control should target the critical ages as well as incorporate social and cultural meanings of smoking in China. As important factors related to future smoking trajectories, gender and mothers' smoking status should also be considered in anti-smoking prevention efforts. Meanings associated with smoking status in the future should also be explored especially for female adolescents.

Background: The bioSocial Cognitive Theory (bSCT) hypothesizes two pathways linking dimensions of impulsivity to substance use. The first predicts that the association between reward sensitivity and substance use is mediated by positive outcome expectancies. The second predicts that the relationship between rash impulsiveness and substance use is mediated by refusal self-efficacy. This model has received empirical support in studies of alcohol use. The present research provides the first application of bSCT to a cannabis treatment population and aims to extend its utility to understanding cannabis use and severity of dependence., Design: 273 patients referred for cannabis treatment completed a clinical assessment that contained measures of interest., Setting: A public hospital alcohol and drug clinic., Measurements: The Sensitivity to Reward Scale, Dysfunctional Impulsivity Scale, Cannabis Expectancy Questionnaire, Cannabis Refusal Self-Efficacy Questionnaire and Severity of Dependence Scale-Cannabis were completed, along with measures of cannabis consumption., Findings: The bSCT model provided a good fit to the data for cannabis use and severity of dependence outcomes. The association between reward sensitivity and each cannabis outcome was fully mediated by positive cannabis expectancies and cannabis refusal self-efficacy. The relationship between rash impulsiveness and each cannabis outcome was fully mediated by cannabis refusal self-efficacy., Conclusions: Findings support the application of the bSCT model to cannabis use and dependence severity and highlight the important role of social cognitive mechanisms in understanding the association between impulsivity traits and these outcomes. The differential association of impulsivity traits to social cognition may assist targeted treatment efforts., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Alexithymia is a personality trait associated with emotion regulation difficulties. Up to 67% of alcohol-dependent patients in treatment have alexithymia. Objectives: The objective of this study was to investigate the direct and indirect effects of alexithymia, negative mood (stress, anxiety, and depression) and alcohol craving on alcohol dependence severity. Methods: Three hundred and fifty-five outpatients (mean age = 38.70, SD = 11.00, 244 males, range 18-71 years) undergoing Cognitive-Behavioral Therapy for alcohol dependence completed the Toronto Alexithymia Scale (TAS-20), Depression Anxiety Stress Scales (DASS-21), Obsessive Compulsive Drinking Scale (OCDS), and Alcohol Use Disorders Identification Test (AUDIT) prior to the first treatment session. Results: Alexithymia had an indirect effect on alcohol dependence severity, via both negative mood and alcohol craving ( b  = 0.03, seb  = 0.008, 95% CI: 0.02-0.05). An indirect effect of negative mood on alcohol dependence via alcohol craving was also observed ( b  = 0.12, seb  = 0.03, 95% CI: 0.07-0.16). Conclusions/importance: Alexithymia worked through negative mood and alcohol craving leading to increased alcohol dependence severity, indicating that craving had an indirect effect on the relationship between alexithymia and alcohol dependence severity. Targeting alcohol craving and negative mood for alcohol-dependent patients with alexithymia seems warranted.

Several studies have established that Major depressive disorder is associated with excess inflammation with an elevation of both pro and anti-inflammatory cytokines in major depressive disorder. In addition, individuals with major depressive disorder are at higher risk of developing coronary artery disease. The role of innate immunity and NFκB-mediated inflammation in depression and its increased association with coronary artery disease is yet to be fully elucidated. Polymorphisms in the Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat and Pyrin Domain Containing 12 (NLRP12), are associated with depression and coronary artery disease in trauma exposed individuals. In a cohort of Vietnam War veterans (n = 299) NLRP12 polymorphisms were analysed for association with depression and coronary calcium scores. The NLRP12 polymorphism, rs34436714 was associated with a higher DASS21 Score for depression (p = 0.037). NLRP12 polymorphisms rs34971363 and rs6509825 (p = 0.022 and p = 0.020) were associated with raised coronary calcium score. To our knowledge, this is the first time rs34436714 has been investigated in Vietnam veterans identifying AC as a risk genotype for depression in Caucasian cohorts. It is also the first time the rs34971363 (CG) and rs6509825 (CT) genotype have been associated with raised coronary calcium score., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Posttraumatic stress disorder (PTSD) is a serious condition that emerges following trauma exposure and involves long-lasting psychological suffering and health-issues. Uncovering critical genes and molecular networks is essential to understanding the biology of the disorder. We performed a genome-wide scan to identify transcriptome signatures of PTSD., Methods: Genome-wide peripheral blood transcriptomic data from 380 service personnel were investigated. This included a discovery sample of 96 Australian Vietnam War veterans and two independent pre and post-deployment replication samples of U.S. Marines (N = 188 and N = 96)., Results: A total of 60 transcripts were differentially expressed between veterans with and without PTSD, surviving Bonferroni multiple testing correction. Genes within the cytokine-cytokine receptor interaction, Jak-STAT signaling and Toll-like receptor signaling pathways were enriched. For 49% of the genes, gene expression changes were also accompanied by DNA methylation changes. Using replication data from two U.S. Marine cohorts, we observed that of the differentially expressed genes, 71% genes also showed significant gene expression changes between pre and post-deployment. Weighted gene co-expression networks revealed two modules of genes associated with PTSD. The first module (67 genes, p-value = 6e-4) was enriched for genes within the 11p13 locus including BDNF. The second module (266 genes, p-value = 0.01) was enriched for genes in 17q11 including SLC6A4, STAT5A and STAT5B., Conclusions: We identified novel transcriptomic loci and biological pathways for PTSD in service personnel. Network analysis revealed enrichment of loci harboring key candidate genes in PTSD. These findings highlight the role of transcriptional biomarkers in the molecular etiology of PTSD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: This study aimed to develop and validate a shortened version of the Drinking Refusal Self-Efficacy Questionnaire-Revised Adolescent version (DRSEQ-RA) using a large sample of adolescents., Methods: Secondary school students (N = 2609, M = 14.52 years, SD = 0.94) completed the DRSEQ-RA (consisting of subscales: Social Pressure; Opportunistic; Emotional Relief) and the Alcohol Use Disorders Identification Test (AUDIT). These data were analysed using non-parametric item response theory (NIRT) including Mokken scalability coefficients, and confirmatory factor analysis., Results: Social Pressure subscale items were better able to distinguish between adolescents with lower or higher levels of drinking refusal self-efficacy, while the Opportunistic and Emotional Relief subscale items were able to distinguish adolescents with low drinking-refusal self-efficacy. The DRSEQ-RA was reduced from 19-items to a 9-item scale and retained the original three-factor structure. The reduced scale was named the Drinking Refusal Self-Efficacy Questionnaire-Shortened Revised Adolescent version (DRSEQ-SRA). The DRSEQ-RA and the DRSEQ-SRA have almost identical psychometric properties. They both demonstrated good fit to the data, each explained 18% of the variance in alcohol consumption, Adj. R 2  = 0.18, p < .001 respectively. The DRSEQ-RA and the DRSEQ-SRA also have excellent scale and subscale internal reliability (αs = 0.92-0.99)., Conclusions: The DRSEQ-SRA is a short, 9-item, measure of adolescent drinking-refusal self-efficacy which demonstrates both reliability and validity. A significant advantage is brevity. The DRSEQ-SRA may be a valuable tool for identifying risk of adolescent drinking and prevention/treatment planning in settings where survey administration time is critical., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Aims: Modification of elevated positive expectations of alcohol consumption (alcohol outcome expectancies; AOEs) is a key feature of Cognitive Behaviour Therapy (CBT) approaches to Alcohol Use Disorders (AUDs). Despite extensive research supporting the efficacy of CBT for AUD, few studies have examined AOE change. This study aimed to assess AOE change following completion of CBT for AUD and its association with drinking behaviour., Method: One-hundred and seventy-five patients who completed a 12-week CBT program for AUD were administered the Drinking Expectancy Questionnaire (DEQ) at pre-treatment assessment and upon completion of treatment. Abstinence was achieved by 108 (61.7%) of completing patients. For patients who lapsed, the mean proportion of abstinent days was 93%., Results: DEQ scales assessing expectations of positive alcohol effects on tension reduction, assertiveness, and cognitive enhancement were significantly lower post-treatment (p<0.001). Expectations of negative effects on mood were higher post-treatment (p<0.001). The largest AOE change occurred on the tension reduction scale. Greater percentage of abstinent days over treatment was associated with lower pre-and post-treatment tension reduction expectancy scores (p<0.05). Drinking during treatment was associated with smaller changes in expectations of negative effects of alcohol on mood (p<0.05)., Conclusions: Individuals who completed CBT treatment for AUD showed significant AOE change. Tension reduction and affective change expectancies may be particularly important for abstinence and useful markers of lapse risk., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To explore the perceptions, attitudes, beliefs, and experiences related to Vietnamese medical students' binge drinking., Design: A qualitative study comprising semi-structured focus groups/interviews with medical students and semi-structured interviews with key informants. Thematic analysis of data., Setting: Participants were a convenience sample of usual volunteers from a medical university in Viet Nam., Participants: 19 medical students from year 1 to 6 and 4 key informants agreed to participate in the study., Results: The study found participants believe medical students drink less than other students and are not binge drinkers yet they experience and/or witness many binge drinking occasions among medical students. Participants consider alcohol use as culturally acceptable in Vietnamese society and a way for medical students to create and improve relationships with their friends, teachers, or work colleagues. Group affiliation and peer pressure to drink excessive alcohol are identified among medical students, especially male students., Conclusion: The culture of drinking behaviour was explored among medical students in Viet Nam. This study reveals a dichotomy between the belief of not being binge drinkers and the experience of many binge drinking occasions among medical students. This tension suggests future research about binge drinking behaviour of Vietnamese medical students is required., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Accelerated epigenetic aging, the difference between the DNA methylation-predicted age (DNAm age) and the chronological age, is associated with a myriad of diseases. This study investigates the relationship between epigenetic aging and risk and protective factors of PTSD. Genome-wide DNA methylation analysis was performed in 211 individuals including combat-exposed Australian veterans (discovery cohort, n = 96 males) and trauma-exposed civilian males from the Grady Trauma Project (replication cohort, n = 115 males). Primary measures included the Clinician Administered PTSD Scale for DSM-5 and the Connor-Davidson Resilience Scale (CD-RISC). DNAm age prediction was performed using the validated epigenetic clock calculator. Veterans with PTSD had increased PTSD symptom severity (P-value = 3.75 × 10 -34 ) and lower CD-RISC scores (P-value = 7.5 × 10 -8 ) than veterans without PTSD. DNAm age was significantly correlated with the chronological age (P-value = 3.3 × 10 -6 ), but DNAm age acceleration was not different between the PTSD and non-PTSD groups (P-value = 0.24). Evaluating potential protective factors, we found that DNAm age acceleration was significantly associated with CD-RISC resilience scores in veterans with PTSD, these results remained significant after multiple testing correction (P-value = 0.023; r = 0.32). This finding was also replicated in an independent trauma-exposed civilian cohort (P-value = 0.02; r = 0.23). Post-hoc factor analyses revealed that this association was likely driven by "self-efficacy" items within the CD-RISC (P-value = 0.015; r = 0.35). These results suggest that among individuals already suffering from PTSD, some aspects of increased resilience might come at a biological cost.

Aims: This study aimed to validate the Drinking Expectancy Questionnaire-Adolescent version (DEQ-A) in a large adolescent sample and to develop and validate a brief measure, the Drinking Expectancy Questionnaire-Shortened Adolescent version (DEQ-SA)., Design and Methods: Cross-sectional survey of secondary school students (n = 2357, aged 13-16, M = 14.66 years, SD = 0.60). Students completed the DEQ-A in school, and measures of alcohol consumption including the Alcohol Use Disorders Identification Test-Consumption. The data were randomly split, and Exploratory Factor Analysis was performed using subsample 1, and Confirmatory Factor Analysis and reliability and validity testing were performed using subsample 2., Results: The 24-item DEQ-A was successfully reduced to 12 items (DEQ-SA) without compromising psychometric properties. The DEQ-A and the DEQ-SA both demonstrated adequate-to-good fit to the data and very good internal reliability. The DEQ-A and DEQ-SA explained 20 and 18% of the variance in alcohol consumption. Adolescents who drank endorsed more positive alcohol expectancies, whereas alcohol-naïve adolescents scored higher on negative alcohol expectancies. As the DEQ-SA comprises two subscales of the DEQ-A, the endorsement rates are applicable to both scales., Discussion and Conclusions: The DEQ-A and the short form of this scale developed in this study (DEQ-SA) show good reliability, internal structure and account for a large proportion of variance in alcohol consumption. Both scales can assist in targeting cognitive change processes within tailored alcohol prevention and treatment approaches, and investigating hypothesised mechanisms of change. The DEQ-SA is recommended for more time-limited environments. [Patton KA, Connor JP, Rundle-Thiele S, Dietrich T, Young RM, Gullo MJ. Validation of the Adolescent Drinking Expectancy Questionnaire and development of a short form., (© 2017 Australasian Professional Society on Alcohol and other Drugs.)

Introduction: China has the world's greatest number of smokers but theory-based smoking interventions are rare. To develop an effective intervention, understanding the determinants of Chinese adolescent smoking is crucial. The Theory of Planned Behavior (TPB) is empirically supported to predict and assist in informing intervention strategies to change health-related behaviors. Based on the TPB, the elicitation of shared smoking beliefs among adolescents can inform future intervention designs among this at-risk population., Methods: We investigated the beliefs from six focus groups (N = 30) of one senior secondary school in Kunming, Yunnan Province, China. We used semi-structured questions based on the TPB framework, including prompts about behavioral (advantages and disadvantages), normative (important referents), and control (barriers and facilitators) beliefs. Following the Consensual Qualitative Research (CQR) methodology, data were discussed until consensus was reached. Auditing was undertaken by an external researcher., Results: Seven domains (advantages, disadvantages, approvers, disapprovers, facilitators, barriers, and smoker images) were examined. Smoking as a gendered behavior, smoking as influenced by cultural and environmental contexts, smoking as a strategy to cope with stress, and awareness of the harm of smoking, are highlighted themes across domains. Data suggested an extended-TPB framework as an appropriate approach to adopt when addressing smoking beliefs among the target population., Conclusions: These beliefs can be utilized to inform future school-based interventions and public health campaigns targeting smoking among Chinese adolescents., Implications: A modified TPB approach has potential for future smoking interventions among Chinese adolescents. Beliefs elicited in this study form a strong basis for designing a location- and population-specific antismoking programme., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Impulsivity is a core characteristic of externalizing problems and a robust predictor of alcohol use in adolescence. There is little evidence on the causal mechanisms through which impulsivity influences drinking or how they are affected by key social factors (peer influence). This study reports the development of the first comprehensive laboratory model of adolescent impulsivity and alcohol use. One-hundred and twenty adolescents (50% female) of legal drinking age (M = 19.47 years, SD = 1.12) in Australia (18+ years) were subjected to 1 of 3 experimental manipulations to increase impulsive behavior (reward cue exposure, negative mood induction, ego depletion). Changes in disinhibition (stop-signal task) and reward-seeking (BAS-Fun Seeking) were measured before completing a laboratory drinking task alone or with a heavy-drinking confederate. Reward cue exposure increased alcohol consumption, with the effect mediated by increased reward-seeking. Negative mood induction increased disinhibition, but not drinking. The presence of a heavy-drinking peer directly increased alcohol consumption in an additive fashion. Findings provide causal evidence that extends survey-based research by highlighting the role of reward-related impulsivity in adolescent alcohol use. The new laboratory model can provide novel insights into the psychological processes underlying adolescent impulsivity and impulsivity-related drinking., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Epigenetic aging is associated with several biological mechanisms and diseases. We assessed two brain data sets, one small (n = 48) and one large (n = 392), to test epigenetic aging in schizophrenia. DNA methylation age from frontal cortex was significantly correlated with chronological age but no significant differences in DNA methylation age acceleration between schizophrenia cases and controls were observed in both data sets. Our results were consistent with a previous study investigating schizophrenia and epigenetic aging in superior temporal gyrus. Future studies targeting different brain regions and defined cell types are warranted to further investigate accelerated brain aging in schizophrenia.

The nitric oxide pathway in the hippocampus is involved in the biological stress response with detrimental consequences to cells and HPA axis feedback. Hippocampal atrophy and HPA axis feedback dysfunction are associated with posttraumatic stress disorder (PTSD). This study systematically investigates two genes of the nitric oxide pathway NOS1AP and NOS1 for a potential involvement in PTSD, comorbidities and resilience. A cohort of age and gender matched Vietnam veterans including trauma-exposed cases and controls was recruited and comprehensively assessed (n=299). A total of 49 NOS1AP and 16 NOS1 polymorphisms were analysed and genotypes correlated with gold standard clinical measures to assess PTSD severity and related phenotypes (depression, anxiety, stress, resilience) based on diagnostic status. Multiple NOS1AP polymorphisms were associated across all measures, and NOS1 polymorphisms were associated with PTSD severity, stress and resilience. The GG genotype of NOS1 polymorphism rs10744891 was associated with PTSD severity (surviving multiple correction) while the combined TT-TG genotypes were associated with resilience (p=0.005; p=0.033, respectively). This study indicates that NOS1AP and NOS1 from the nitric oxide pathway are likely to play a key role in PTSD, its comorbidities and resilience. Given the essential role of NOS1AP and NOS1 in stress response they may be reliable targets for screening and intervention strategies., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Objectives: To examine the combined effect of the BDNF Val66Met (rs6265) polymorphism and BDNF DNA methylation on transcriptional regulation of the BDNF gene., Methods: DNA methylation profiles were generated for CpG sites proximal to Val66Met, within BDNF promoter I and exon V for prefrontal cortex samples from 25 schizophrenia and 25 control subjects. Val66Met genotypes and BDNF mRNA expression data were generated by transcriptome sequencing. Expression, methylation and genotype data were correlated and examined for association with schizophrenia., Results: There was 43% more of the BDNF V-VIII-IX transcript in schizophrenia samples. BDNF mRNA expression and DNA methylation of seven CpG sites were not associated with schizophrenia after accounting for age and PMI effects. BDNF mRNA expression and DNA methylation were not altered by Val66Met after accounting for age and PMI effects. DNA methylation of one CpG site had a marginally significant positive correlation with mRNA expression in schizophrenia subjects., Conclusions: Schizophrenia risk was not associated with differential BDNF mRNA expression and DNA methylation. A larger age-matched cohort with comprehensive clinical history is required to accurately identify the effects of genotype, mRNA expression and DNA methylation on schizophrenia risk.

Objective: To determine whether the prevalence of physical comorbidities in Australian Vietnam War veterans with post-traumatic stress disorder (PTSD) is higher than in trauma-exposed veterans without PTSD., Design, Setting and Participants: Cross-sectional analysis of the health status (based on self-reported and objective clinical assessments) of 298 Australian Vietnam War veterans enrolled by the Gallipoli Medical Research Institute (Brisbane) during February 2014 - July 2015, of whom 108 were confirmed as having had PTSD and 106 served as trauma-exposed control participants.Main outcomes and measures: Diagnostic psychiatric interview and psychological assessments determined PTSD status, trauma exposure, and comorbid psychological symptoms. Demographic data, and medical and sleep history were collected; comprehensive clinical examination, electrocardiography, spirometry, liver transient elastography, and selected pathology assessments and diagnostic imaging were performed. Outcomes associated with PTSD were identified; regression analysis excluded the effects of potentially confounding demographic and risk factors and comorbid symptoms of depression and anxiety., Results: The mean total number of comorbidities was higher among those with PTSD (17.7; SD, 6.1) than in trauma-exposed controls (14.1; SD, 5.2; P < 0.001). For 24 of 171 assessed clinical outcomes, morbidity was greater in the PTSD group, including for conditions of the gastrointestinal, hepatic, cardiovascular, and respiratory systems, sleep disorders, and laboratory pathology measures. In regression analyses including demographic factors, PTSD remained positively associated with 17 adverse outcomes; after adjusting for the severity of depressive symptoms, it remained significantly associated with ten., Conclusion: PTSD in Australian Vietnam veterans is associated with comorbidities in several organ systems, independent of trauma exposure. A comprehensive approach to the health care of veterans with PTSD is needed.

Background: Posttraumatic stress disorder (PTSD) is associated with increased inflammation and comorbid medical conditions. However, study findings for individual inflammatory marker levels have been inconsistent. Some research suggests that resilience may play a role in decreased inflammation. A polymorphism in the promoter region of the tumor necrosis factor α gene (TNFα), TNFA -308 (rs1800629) is associated with psychiatric illness but its role in PTSD is yet to be elucidated., Objective: This study investigates a key inflammatory marker, TNFα, for its role in PTSD severity., Method: In a cohort of trauma-exposed Vietnam War veterans (n=299; 159 cases, 140 controls) TNF α serum levels and TNFα polymorphism rs1800629 were correlated with PTSD severity and resilience scores., Results: The polymorphism was associated with PTSD severity (p=0.045). There were significant group differences between cases and controls with regards to serum TNFα levels (p=0.036). Significant correlations were found between PTSD severity and elevated TNFα levels (r=0.153; p=0.009), and between resilience and decreased TNFα levels at a trend level (p=0.08) across the entire cohort. These relationships were non-significant after controlling for covariates. In the PTSD diagnostic group, a correlation of TNFα and PTSD severity was observed on a trend level (p=0.06), the relationship between TNFα and resilience remained non-significant., Conclusions: To our knowledge, this is the first time rs1800629 has been investigated in PTSD contributing to a growing body of literature that identifies the GG as a risk genotype for psychiatric disorders in Caucasian cohorts. However, more research is needed to replicate our results in larger, equally well-characterized cohorts. The relationship between serum TNFα levels and PTSD severity and resilience requires further investigation., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Background: Due to the heterogeneous nature of schizophrenia, understanding the genetic risk for the disease is a complex task. Gene expression studies have proven to be more reliable than association studies as they are consistently replicated in a tissue specific manner., Methods: Using RNA-Seq we analysed gene expression in the frontal cortex of 24 individuals with schizophrenia and 25 unaffected controls., Results: We identified 1146 genes that were differentially expressed in schizophrenia, approximately 60% of which were up-regulated and 366 of 1146 (32%) also have aberrant DNA methylation (p=2.46×10 -39 ). The differentially expressed genes were significantly overrepresented in several pathways including inflammatory (p=8.7×10 -3 ) and nitric oxide pathways (p=9.2×10 -4 ). Moreover, these genes were significantly enriched for those with a druggable genome (p=0.04). We identified a number of genes that are significantly up-regulated in schizophrenia as confirmed in other gene expression studies using different brain tissues. Of the 349 genes associated with schizophrenia from the Psychiatric Genomics Consortium we identified 16 genes that are significant from our list of differentially expressed genes., Conclusions: Our results identified biological functional genes that are differentially expressed in schizophrenia. A subset of these genes are clinically proven drug targets. We also found a strong pattern of differentially expressed immune response genes that may reflect an underlying defect in schizophrenia., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Serotonin receptor 2A ( HTR2A ) is an important signalling factor implicated in cognitive functions and known to be associated with schizophrenia. The biological significance of HTR2A in schizophrenia remains unclear as molecular analyses including genetic association, mRNA expression and methylation studies have reported inconsistent results. In this study, we examine HTR2A expression and methylation and the interaction with HTR2A polymorphisms to identify their biological significance in schizophrenia. Subjects included 25 schizophrenia and 25 control post-mortem brain samples. Genotype and mRNA data was generated by transcriptome sequencing. DNA methylation profiles were generated for CpG sites within promoter-exon I region. Expression, genotype and methylation data were examined for association with schizophrenia. HTR2A mRNA levels were reduced by 14% ( p = 0.006) in schizophrenia compared to controls. Three CpG sites were hypermethylated in schizophrenia (cg5 p = 0.028, cg7 p = 0.021, cg10 p = 0.017) and HTR2A polymorphisms rs6314 ( p = 0.008) and rs6313 ( p = 0.026) showed genetic association with schizophrenia. Differential DNA methylation was associated with rs6314 and rs6313. There was a strong correlation between HTR2A DNA methylation and mRNA expression. The results were nominally significant but did not survive the rigorous Benjamini-Hochberg correction for multiple testing. Differential HTR2A expression in schizophrenia in our study may be the result of the combined effect of multiple differentially methylated CpG sites. Epigenetic HTR2A regulation may alter brain function, which contributes to the development of schizophrenia., Competing Interests: The authors declare no conflict of interest.

Background: Standardized alcohol craving scales are rarely used outside of research environments despite recognized clinical utility. Scale length is a key barrier to more widespread application. A brief measure of alcohol craving is needed to improve research and treatment of alcohol use disorders (AUDs). Grounded in the Elaborated Intrusion Theory of Desire, the Alcohol Craving Experience (ACE) Questionnaire comprises two 11-item self-report scales that assess past-week frequency and maximum strength of alcohol craving. This study aimed to create a brief version of the ACE while maintaining psychometric integrity and clinical utility., Methods: Patients attending a university hospital alcohol and drug outpatient service for the treatment of AUD completed the ACE as part of a questionnaire battery. Three patient samples were utilized: 519 patients with pretreatment and outcome data, 228 patients with pretreatment data, and 66 patients who completed the ACE at treatment sessions 1 and 2., Results: The Frequency scale of the ACE possessed greater clinical utility and predictive validity than the Strength scale. Revision of the Frequency measure produced a 5-item "Mini Alcohol Craving Experience" (MACE) Questionnaire. Satisfactory validity (construct, predictive, concurrent, convergent, and incremental) and reliability (internal and test-retest) were maintained. A 1 standard deviation increase in pretreatment MACE score was associated with a 54 percentage increase in the odds of patient lapse or dropout., Conclusions: The MACE provides a brief, theoretically, and psychometrically robust measure of alcohol craving suitable for use with AUD populations in time-limited clinical and research settings., (Copyright © 2016 by the Research Society on Alcoholism.)

Background and Aims: Relatively few cannabis dependent individuals seek treatment and little is known about the determinants of treatment seeking. Social Cognitive Theory (SCT) provides a useful framework for examining human behaviour and motivation which may be helpful in explaining treatment seeking. This study examined the differences in cannabis outcome expectancies and cannabis refusal self-efficacy between treatment seekers and non-treatment seekers with cannabis dependence., Design: Non-treatment seekers were referred to an illicit drug diversion program. Treatment seekers commenced an outpatient cannabis treatment program and completed a comprehensive assessment that included measures of cannabis outcome expectancies and refusal self-efficacy., Setting: A public hospital alcohol and drug outpatient clinic., Participants: 269 non-treatment seekers and 195 individuals commencing cannabis dependence treatment., Measurements: The Cannabis Expectancy Questionnaire (CEQ), Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ), Severity of Dependence Scale - Cannabis (SDS-C), General Health Questionnaire (GHQ-28) and Readiness to Change Questionnaire (RTC) were completed., Findings: Treatment seekers had significantly higher levels of negative cannabis outcome expectancies and significantly lower levels of emotional relief refusal self-efficacy (belief in ability to resist using cannabis when experiencing negative affect) (ps<0.001). Treatment seekers had significantly higher levels of psychological distress and self-perceived cannabis dependence compared to non-treatment seekers (ps<0.001)., Conclusions: High negative cannabis outcome expectancies and low emotional relief refusal self-efficacy may play a key role in motivation to seek treatment., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Drug-related outcomes expectancies and refusal self-efficacy are core components of Social Cognitive Theory. Both predict treatment outcome in alcohol use disorders. Few studies have reported expectancies and refusal self-efficacy in cannabis dependence. None have examined both, although both constructs are key targets in Cognitive-Behavioural Therapy (CBT). This study tests the predictive role of expectancies and refusal self-efficacy in treatment outcome for cannabis dependence., Design: Outpatients completed a comprehensive assessment when commencing cannabis treatment and predictors of treatment outcome were tested., Setting: A university hospital alcohol and drug outpatient clinic., Participants: 221 cannabis-dependent patients participated in a 6-week CBT program where the goal was abstinence., Measurements: Cannabis Expectancy Questionnaire and Cannabis Refusal Self-Efficacy Questionnaire, cannabis dependence severity [Severity of Dependence Scale], psychological distress [General Health Questionnaire] at baseline; the timeline follow-back procedure at baseline and each session., Findings: Patients reporting lower confidence in their ability to resist cannabis during high negative affect (emotional relief refusal self-efficacy) had a lower likelihood of abstinence (p=0.004), more days of use (p<0.001), and larger amount used (p<0.001). Negative cannabis expectancies predicted greater likelihood of abstinence (p=0.024). Higher positive expectancies were associated with lower emotional relief self-efficacy, mediating its association with outcome (p<0.001)., Conclusions: Emotional relief refusal self-efficacy and negative expectancies are predictive of better treatment outcomes for cannabis dependence. Positive expectancies may indirectly predict poorer outcome because of a negative association with self-efficacy, but this conclusion remains tentative as directionality could not be established., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Impulsivity predicts alcohol misuse and risk for alcohol use disorder. Cognition mediates much of this association. Genes also account for a large amount of variance in alcohol misuse, with dopamine and serotonin receptor genes of particular interest, because of their role in motivated behavior. The precise psychological mechanisms through which such genes confer risk is unclear. Trait impulsivity conveys risk for alcohol misuse by influencing two distinct domains of cognition: beliefs about the reinforcing effects of alcohol consumption (positive alcohol expectancy) and the perceived ability to resist it (drinking refusal self-efficacy). This study investigated the effect of the dopamine-related polymorphism in the DRD2/ANKK1 gene (rs1800497) and a serotonin-related polymorphism in the HTR2A gene (rs6313) on associations between impulsivity, cognition, and alcohol misuse in 120 emerging adults (18-21years). HTR2A predicted lower positive alcohol expectancy, higher refusal self-efficacy, and lower alcohol misuse. However, neither polymorphism moderated the linkages between impulsivity, cognition, and alcohol misuse. This is the first report of an association between HTR2A and alcohol-related cognition. Theoretically-driven biopsychosocial models have potential to elucidate the specific cognitive mechanisms through which distal risk factors like genes and temperament affect alcohol misuse in emerging adulthood., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction and Aims: This study investigated the extent to which parental monitoring and parental disapproval of alcohol use account for the association between country of birth and adolescent alcohol use., Design and Methods: The sample consisted of 10 273 adolescents from grades 7 (Mean age = 12.5 years), 9 (14.5 years) and 11 (16.4 years) in Victoria, Australia. Participants completed a questionnaire during class time. Mediation analyses were performed to examine the extent to which parental monitoring and parental disapproval of alcohol use accounted for variations in past 30 day alcohol use between Australian-born and immigrant adolescents., Results: Alcohol use in the past 30 days ranged from 8.0% to 44.4% for participants from different countries/regions of birth. Those born in Asia (odds ratio 0.20-0.51, P < 0.05) and Africa (odds ratio 0.45, P < 0.01) were much less likely to have consumed alcohol compared to those born in Australia. Adolescents from these two regions (except for Western Asia) reported higher levels of parental monitoring and parental disapproval of alcohol use (P < 0.05). Higher levels of parental monitoring and parental disapproval of alcohol use partially mediated the association between birth place and alcohol use (P < 0.05)., Discussion and Conclusions: There were large variations in alcohol use between Australian-born and immigrant adolescents from different countries/regions. Adolescents from Asia or Africa were much less likely to consume alcohol, and this protective effect was partially accounted for by parental monitoring and disapproval of alcohol use.[Chan GCK, Kelly AB, Connor JP, Hall WD, Young RM, Williams JW. Does parental monitoring and disapproval explain variations in alcohol use among adolescents from different countries of birth? Drug Alcohol Rev 2016;35:741-749]., (© 2016 Australasian Professional Society on Alcohol and other Drugs.)

Background: Schizophrenia is a clinically heterogeneous disorder and may be explained by its complex genetic architecture. Many schizophrenia susceptibility genes were identified but the picture remains unclear due to inconsistent or contradictory genetic association studies. This confusion may, in part, be because symptoms result from the combined interaction of many genes and these interacting genes are associated with specific sub-phenotypes of schizophrenia rather than schizophrenia as a whole. This study investigates the relationship between schizophrenia susceptibility genes and schizophrenia sub-phenotypes by identifying multiple gene variant interactions., Materials and Methods: Fifty SNPs from 21 genes were genotyped in 235 Australian participants with schizophrenia screened for various phenotypes. Schizophrenia participants were grouped into relevant phenotype clusters using cluster analysis and normalized phenotype cluster scores were calculated for each patient. The relationship between genotypes and normalized phenotype cluster scores were analyzed by linear regression analysis., Results: Three phenotype clusters were identified. There was some overlap in symptoms between phenotype clusters, particularly for depression. However, cluster 1 appears to be characterized by speech disorder and affective behavior symptoms, cluster 2 has predominantly hallucination symptoms and cluster 3 has mainly delusion symptoms. Interaction of five SNPs was found to have an effect on cluster 1 symptoms; ten SNPs on cluster 2 symptoms; and eight SNPs on cluster 3 symptoms., Conclusion: The interaction of specific susceptibility genes is likely to lead to specific clinical sub-phenotypes of schizophrenia. Larger patient cohorts with more extensive clinical data will improve the detection of gene interactions and the resultant schizophrenia clinical phenotypes., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Objective: Type 2 diabetes is commonly found in schizophrenia and is an important contributor to mortality and morbidity in this condition. Dopamine has been implicated in the aetiology of both diabetes and schizophrenia. It is possible that both disorders share a common genetic susceptibility., Methods: In a cross-sectional study, we examined 2 dopamine D2 receptor (DRD2) single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia (C939 T, rs6275 and C957 T, rs6277) along with fasting blood glucose and body mass index (BMI) in 207 antipsychotic-treated patients with schizophrenia. All participants met DSM-IV criteria for schizophrenia, and those with other psychiatric disorders were excluded. Analysis of covariance was used to compare fasting glucose results by DRD2 genotypes, after controlling for known confounds. For significant associations, follow-up Bonferroni post hoc tests examined differences in fasting glucose levels between genotypes. Specific comparisons were also made using analysis of variance and chi-square (Fisher's exact test)., Results: The 2 DRD2 risk genotypes were associated with significant increases in blood glucose, after controlling for BMI, age, sex, dosage and type of antipsychotic medication, number of hospitalisations, and negative symptoms (rs6275, F(2, 182) = 5.901, P = 0.003; rs6277 SNP, F(2, 178) = 3.483, P = 0.033)., Conclusions: These findings support the involvement of DRD2 not only in schizophrenia but also in elevated levels of blood glucose commonly found in antipsychotic-treated patients with schizophrenia. Our data support the notion that diabetes may not merely be a comorbid condition but could be fundamentally associated with the pathogenesis of schizophrenia itself., (© The Author(s) 2016.)

Alexithymia and alcohol outcome expectancies were investigated in 355 alcohol-dependent treatment seekers. Patients with alexithymia gave stronger self-report ratings of expectancies of affective change related to beliefs that alcohol leads to negative mood states and assertion, that alcohol enhances social skills, compared to those without alexithymia. The findings suggest that alcohol-dependent outpatients with alexithymia may drink to experience intensified negative emotions and improved social functioning., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Alexithymia is characterized by difficulty identifying feelings, difficulty describing feelings, and an externally oriented thinking style. Alexithymia has been described as a trait-like risk factor for the development of alcohol use disorders. Few studies have investigated the absolute (whether mean scores change over time) and relative (extent to which relative differences among individuals remain the same over time) stability of alexithymia among men and women with alcohol dependence, or have considered potential underlying mechanisms. Social learning processes contribute to and maintain alcohol problems. The reinforcement of alcohol expectancies is one plausible mechanism that links the difficulties in emotional processing associated with alexithymia and alcohol use. The present study investigated the stability of alexithymia as well as alcohol expectancy as a mediator of alexithymia. Three hundred fifty-five alcohol-dependent patients were enrolled in a cognitive behavioral treatment program. Ninety-two alcohol-dependent patients completed assessments at baseline and at 3-month follow-up. Results indicated that total Toronto Alexithymia Scale (TAS-20; Bagby, Parker, & Taylor, 1994) mean score, difficulty identifying feelings, and difficulty describing feelings decreased significantly over time with a larger decrease in alexithymia mean scores for females. Externally oriented thinking mean scores did not change. The TAS-20 and its subfactors demonstrated significant correlations, from baseline to follow-up, which were stronger for males than for females. Regression analyses showed that the total TAS-20 mean scores, difficulty identifying feelings, and difficulty describing feelings were partially mediated through assertion alcohol expectancies. In conclusion, this suggests that alexithymia has relative stability and is a trait-like factor among alcohol-dependent treatment seekers., ((c) 2016 APA, all rights reserved).)