High-intensity drinking in adult Australian twins

Background: Many adult drinkers consume far beyond the binge threshold. This “high-intensity drinking” (HID), defined as 2 (HID-2) and 3 (HID-3) times the binge threshold, is of public health interest due to its role in acute alcohol-related harms. Research on HID has mostly been limited to college-aged young adults, focused on contextual factors, and neglected the potential role of genetic influences on the propensity to engage in HID. Methods: Structured diagnostic interviews assessing past-year alcohol involvement were conducted with 3,785 individuals (1,365 men, 2,420 women; Mage = 32, range = 21 to 46), including 3,314 twins and 471 nontwin siblings from the Australian Twin Registry. Multinomial logistic regression analyses were conducted to compare HID-2 and HID-3 to binge drinking on demographic correlates, drinking characteristics, and drinking-related consequences. Biometric modeling was conducted to estimate the role of genetic, common, and individual-specific environmental factors in HID propensity. Results: Among past-year drinkers, the prevalence of HID-2 and HID-3 was both 22%, with men disproportionally represented. The frequencies of drinking, intoxication, and binge drinking significantly increased across the heavier drinking categories, which also evidenced higher average consumption quantities and higher rates of alcohol-related consequences. The propensity to engage in HID was significantly heritable (A = 37% [95% CI: 28 to 46%]), with individual-specific environmental influences accounting for the remainder of the variance. Conclusions: This study convincingly demonstrates that HID is not restricted to college-aged young adults, but also can be highly prevalent among those of working age, and that the propensity to engage in HID is partially explained by genetic influences. © 2020 by the Research Society on Alcoholis

Overlap of heritable influences between Cannabis Use Disorder, frequency of use and opportunity to use cannabis: Trivariate twin modelling and implications for genetic design

Background: The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use. Methods: A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype. Results: Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency. Conclusions: There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology

Cyan Moon crew preparation for the Sydney To Hobart Yacht Race March 2023

The Collaborative Evaluation & Research Centre (formally CERG) evaluated the crew’s experiences pre and post yacht events using a mixed methods approach. The Cyan yacht had a crew of 12 and competed in a number of events in the racing calendar leading up to the Sydney to Hobart race in January 2023. This was the first time that this boat and many of the crew competed in the Sydney to Hobart yacht race

The association of genetic predisposition to depressive symptoms with non-suicidal and suicidal self-Injuries

Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of depressive symptoms with lifetime NSSI, suicidal ideation, and suicide attempts in a sample of 6237 Australian adult twins and their family members (3740 females, mean age\ua0=\ua042.4\ua0years). Polygenic risk scores for depressive symptoms significantly predicted suicidal ideation, and some predictive ability was found for suicide attempts; the polygenic risk scores explained a significant amount of variance in suicidal ideation (lowest p\ua0=\ua00.008, explained variance ranging from 0.10 to 0.16\ua0%) and, less consistently, in suicide attempts (lowest p\ua0=\ua00.04, explained variance ranging from 0.12 to 0.23\ua0%). Polygenic risk scores did not significantly predict NSSI. Results highlight that individuals genetically predisposed to depression are also more likely to experience suicidal ideation/behaviour, whereas we found no evidence that this is also the case for NSSI

Genetic effects on alcohol dependence risk : Re-evaluating the importance of psychiatric and other heritable risk factors

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk. Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk. Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47% (95% CI 28–55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0% (95% CI 0–14) to shared environmental factors, and 53% (95% CI 45–63) to non-shared environmental influences. Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD

Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins:a retrospective cohort study

Background: Early and frequent cannabis use are associated with an increased likelihood of major depressive disorder (MDD) as well as suicidal thoughts and behaviours. We identify associations between aspects of cannabis use, MDD, and suicidal thoughts and behaviours and examine whether such associations persist after accounting for those predisposing factors, including genetic liability and early family environment, that are shared by identical twins who are discordant for cannabis exposure. Any residual association in such identical pairs might be indicative of individual-specific pathways that might be of a causal nature. Methods: We did a logistic regression analysis of cannabis use from retrospective data on same-sex male and female twin pairs drawn from 3 studies that had recruited twins from the Australian Twin Registry, 1992–93 (sample 1), 1996–2000 (sample 2), and 2005–09 (sample 3). We studied associations between early use and frequent use of cannabis and MDD, suicidal ideation (ever and persistent), and suicide plan and attempt in the full sample as well as in pairs of monozygotic and dizygotic twins that were discordant for each measure of cannabis involvement at a single timepoint. Significant monozygotic associations were further adjusted for covariates, such as early alcohol or nicotine use, early dysphoric or anhedonic mood, conduct disorder, and childhood sexual abuse. Interactions between each cannabis measure and sex, sample or study effects, and birth year category were also examined as covariates. Findings: In 13 986 twins (6181 monozygotic and 7805 dizygotic), cannabis use ranged from 1345 (30·4%) of 4432 people in sample 1 to 2275 (69·0%) of 3299 in sample 3. Mean age of first cannabis use ranged from 17·9 years (SD 3·3) in sample 3 to 21·1 years (5·2) in sample 1, and frequent use (≥100 times) was reported by 214 (15·9%) of 1345 users in sample 1 and 499 (21·9%) of 2275 in sample 3. The prevalence of suicidal ideation ranged from 1102 (24·9%) of 4432 people in sample 1 to 1644 (26·3%) of 6255 people in sample 2 and 865 (26·2%) of 3299 people in sample 3. Prevalence of MDD ranged from 901 (20·3%) people in sample 1 to 1773 (28·3%) in sample 2. The monozygotic twin who used cannabis frequently was more likely to report MDD (odds ratio 1·98, 95% CI 1·11–3·53) and suicidal ideation (2·47, 1·19–5·10) compared with their identical twin who had used cannabis less frequently, even after adjustment for covariates. For early cannabis use, the monozygotic point estimate was not significant but could be equated to the significant dizygotic estimate, suggesting a possible association with suicidal ideation. Interpretation: The increased likelihood of MDD and suicidal ideation in frequent cannabis users cannot be solely attributed to common predisposing factors

Cohort profile : the Australian genetics of depression study

Purpose Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression at some point in their lifetime. The purpose of establishing this cohort is to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants. Participants A total of 20 689 participants were recruited through the Australian Department of Human Services and a media campaign, 75% of whom were female. The average age of participants was 43 years±15 years. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample (75%) were sent a saliva kit in the mail. Findings to date 95% of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a lifetime depressive episode. 68% of the sample report having been diagnosed with another psychiatric disorder in addition to depression. In line with findings from clinical trials, only 33% of the sample report responding well to the first antidepressant they were prescribed. Future plans A number of analyses to investigate the genetic architecture of depression and common comorbidities will be conducted. The cohort will contribute to the global effort to identify genetic variants that increase risk to depression. Furthermore, a thorough investigation of genetic and psychosocial predictors of antidepressant response and side effects is planned. © © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Genetic aetiology of self-harm ideation and behaviour

Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (h) estimates were ~10%, and both traits were highly genetically correlated (LDSC r > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant

The variance shared across forms of childhood trauma is strongly associated with liability for psychiatric and substance use disorders

Introduction: Forms of childhood trauma tend to co-occur and are associated with increased risk for psychiatric and substance use disorders. Commonly used binary measures of trauma exposure have substantial limitations. Methods: We performed multigroup confirmatory factor analysis (CFA), separately by sex, using data from the Childhood Trauma (CT) Study's sample of twins and siblings (N = 2594) to derive three first-order factors (childhood physical abuse, childhood sexual abuse, and parental partner abuse) and, as hypothesized, one higher order, childhood trauma factor (CTF) representing a measure of their common variance. Results: CFA produced a good-fitting model in the CT Study; we replicated the model in the Comorbidity and Trauma (CAT) Study's sample (N = 1981) of opioid-dependent cases and controls. In both samples, first-order factors are moderately correlated (indicating they measure largely unique, but related constructs) and their loadings on the CTF suggest it provides a reasonable measure of their common variance. We examined the association of CTF score with risk for psychiatric and substance use disorders in these samples and the OZ-ALC GWAS sample (N = 1538) in which CT Study factor loadings were applied. We found that CTF scores are strongly associated with liability for psychiatric and substance use disorders in all three samples; estimates of risk are extremely consistent across samples. Conclusions: The CTF is a continuous, robust measure that captures the common variance across forms of childhood trauma and provides a means to estimate shared liability while avoiding multicollinearity. Confirmatory factor analysis was used to derive a higher order, childhood trauma factor representing a measure of the common variance across three forms of trauma: childhood physical abuse, childhood sexual abuse, and parental partner abuse. We replicated the model in a second sample. We then examined the association of childhood trauma score with risk for psychiatric and substance use disorders in these samples and a third sample in which the primary sample's factor loadings were applied finding factor scores to be strongly and consistently associated with liability for psychiatric and substance use disorders in all three samples