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.Enda M Byrne, Katherine M Kirk, Sarah E Medland, John J McGrath, Lucia Colodro-Conde, Richard Parker ... et al

Overlapping genetic and environmental influences on nonsuicidal self-injury and suicidal ideation: Different outcomes, same etiology?

Item does not contain fulltextIMPORTANCE Nonsuicidal self-injury (NSSI) and suicidal self-injury are very harmful behaviors and are associated with several psychiatric disorders. In the recently developed fifth edition of the DSM, NSSI and suicidal behavior disorder are for the first time introduced as conditions in their own right instead of symptoms of other psychiatric disorders. It is unclear to what extent NSSI and suicidal self-injury share the same underlying biological mechanisms and are influenced by the same environmental factors. OBJECTIVE To determine the relative importance of genetic and environmental influences on the variation in NSSI and suicidal ideation and their covariation. DESIGN, SETTING, AND PARTICIPANTS Classical twin design using a sample of 10 678 male and female adult twins (mean [SD] age, 32.76 [6.99] years) from the Australian Twin Registry, a population-based twin registry. Between 1996 and 2009, the twins participated in semistructured telephone interviews that primarily focused on psychiatric disorders. MAIN OUTCOMES AND MEASURES Lifetime presence of self-reported NSSI and suicidal ideation. RESULTS The prevalences of NSSI and suicidal ideation were 4.7% and 26.5%, respectively, and individuals who engaged in self-harm were much more likely to report suicidal ideation (odds ratio = 8.39; 95% CI, 6.84-10.29). Results from a bivariate genetic model indicated that genetic factors explain a substantial part of the variance in both NSSI (37% for men and 59% for women) and suicidal ideation (41% for men and 55% for women), while residual influences (including nonshared environmental influences and measurement error) explain the remainder of the variance. Shared (family) environment did not seem to play a role. Moreover, both behaviors were strongly correlated (r = 0.49 for men and 0.61 for women), and this correlation was largely explained by overlapping genetic influences (76% for men and 62% for women), whereas residual influences accounted for the remainder of the phenotypic correlation. CONCLUSIONS AND RELEVANCE Results indicated that the substantial correlation between NSSI and suicidal ideation is largely driven by overlapping genetic factors, suggesting that the 2 behaviors share similar biological underpinnings. Overlapping residual influences also explain part of the covariance between the 2 traits. Future research should further investigate which genetic and environmental influences underlie the vulnerability to NSSI and suicidal ideation.7 p

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

Contains fulltext : 162902.pdf (publisher's version ) (Open Access)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 = 42.4 years). 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 = 0.008, explained variance ranging from 0.10 to 0.16 %) and, less consistently, in suicide attempts (lowest p = 0.04, explained variance ranging from 0.12 to 0.23 %). 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.8 p

Major depressive disorder, suicidal ideation, and suicide attempt in twins discordant for cannabis dependence and early-onset cannabis use

Background: Previous research has reported both a moderate degree of comorbidity between cannabis dependence and major depressive disorder (MDD) and that early-onset cannabis use is associated with increased risks for MDD. Objective: To examine whether associations between both lifetime cannabis dependence and early cannabis use and measures of MDD, suicidal ideation, and suicide attempt persist after controlling for genetic and/or shared environmental influences. Design: Cross-sectional survey of twin pairs discordant for lifetime cannabis dependence and those discordant for early cannabis use. Setting: General population sample of twins (median age, 30 years). Participants: Two hundred seventy-seven same-sex twin pairs discordant for cannabis dependence and 311 pairs discordant for early-onset cannabis use (before age 17 years). Main Outcome Measures: Self-report measures of DSM-IV–defined lifetime MDD, suicidal ideation, and suicide attempt. Results: Individuals who were cannabis dependent had odds of suicidal ideation and suicide attempt that were 2.5 to 2.9 times higher than those of their non–cannabis-dependent co-twin. Additionally, cannabis dependence was associated with elevated risks of MDD in dizygotic but not in monozygotic twins. Those who initiated cannabis use before age 17 years had elevated rates of subsequent suicide attempt (odds ratio, 3.5 [95% confidence interval, 1.4-8.6]) but not of MDD or suicidal ideation. Early MDD and suicidal ideation were significantly associated with subsequent risks of cannabis dependence in discordant dizygotic pairs but not in discordant monozygotic pairs. Conclusions: Comorbidity between cannabis dependence and MDD likely arises through shared genetic and environmental vulnerabilities predisposing to both outcomes. In contrast, associations between cannabis dependence and suicidal behaviors cannot be entirely explained by common predisposing genetic and/or shared environmental predispositions. Previously reported associations between early-onset cannabis use and subsequent MDD likely reflect shared genetic and environmental vulnerabilities, although it remains possible that early-onset cannabis use may predispose to suicide attempt

The relationship between cannabis involvement and suicidal thoughts and behaviors

Background: In the present study, we examined the relationship between cannabis involvement and suicidal ideation (SI), plan and attempt, differentiating the latter into planned and unplanned attempt, taking into account other substance involvement and psychopathology. Methods: We used two community-based twin samples from the Australian Twin Registry, including 9583 individuals (58.5% female, aged between 27 and 40). The Semi-Structured Assessment of the Genetics of Alcoholism (SSAGA) was used to assess cannabis involvement which was categorized into: (0) no cannabis use (reference category); (1) cannabis use only; (2) 1-2 cannabis use disorder symptoms; (3) 3 or more symptoms. Separate multinomial logistic regression analyses were conducted for SI and suicide attempt with or without a plan. Twin analyses examined the genetic overlap between cannabis involvement and SI. Results: All levels of cannabis involvement were related to SI, regardless of duration (odds ratios [ORs]. = 1.28-2.00, p. 0.10). Associations persisted even after controlling for other psychiatric disorders and substance involvement. Overlapping genetic (rG= 0.45) and environmental (rE= 0.21) factors were responsible for the covariance between cannabis involvement and SI. Conclusions: Cannabis involvement is associated, albeit modestly, with SI and unplanned suicide attempts. Such attempts are difficult to prevent and their association with cannabis use and cannabis use disorder symptoms requires further study, including in different samples and with additional attention to confounders

Cannabis involvement and nonsuicidal self-injury: A discordant twin approach

Item does not contain fulltextOBJECTIVE: Cannabis use, particularly at an early age, has been linked to suicidal thoughts and behavior, but minimal work has examined the association between cannabis use and lifetime nonsuicidal self-injury (NSSI). The current study aims to characterize the overlap between lifetime and early cannabis use and NSSI and to examine genetic and environmental mechanisms of this association. METHOD: Adult male and female twins from the Australian Twin Registry (N = 9,583) were used to examine the odds of NSSI associated with lifetime cannabis use and early cannabis use (i.e., <17 years of age). These associations were also examined within monozygotic (MZ) twins discordant for cannabis use and MZ twins discordant for early cannabis use. Analyses were replicated in an independent sample of female twins (n = 3,787) accounting for the age at onset of cannabis use and NSSI. RESULTS: Lifetime cannabis use (odds ratio [OR] = 2.84, 95% CI [2.23, 3.61]) and early cannabis use were associated with increased odds of NSSI (OR = 2.15, 95% CI [1.75, 2.65]), and this association remained when accounting for covariates. The association was only significant, however, in MZ twin pairs discordant for early cannabis use (OR = 3.20, 95% CI [1.17, 8.73]). Replication analyses accounting for the temporal ordering of cannabis use and NSSI yielded similar findings of nominal significance. CONCLUSIONS: Results suggest that NSSI is associated with cannabis involvement via differing mechanisms. For lifetime cannabis use, the lack of association in discordant pairs suggests the role of shared genes and family environment. However, in addition to such shared familial influences, person-specific and putatively causal factors contribute to the relationship between early cannabis use and NSSI. Therefore, delaying the onset of cannabis use may reduce exposure to influences that exacerbate vulnerabilities to NSSI.8 p

The relationship between cannabis involvement and suicidal thoughts and behaviors

Background In the present study, we examined the relationship between cannabis involvement and suicidal ideation (SI), plan and attempt, differentiating the latter into planned and unplanned attempt, taking into account other substance involvement and psychopathology. Methods We used two community-based twin samples from the Australian Twin Registry, including 9583 individuals (58.5% female, aged between 27 and 40). The Semi-Structured Assessment of the Genetics of Alcoholism (SSAGA) was used to assess cannabis involvement which was categorized into: (0) no cannabis use (reference category); (1) cannabis use only; (2) 1-2 cannabis use disorder symptoms; (3) 3 or more symptoms. Separate multinomial logistic regression analyses were conducted for SI and suicide attempt with or without a plan. Twin analyses examined the genetic overlap between cannabis involvement and SI. Results All levels of cannabis involvement were related to SI, regardless of duration (odds ratios [ORs] = 1.28-2.00, p 0.10). Associations persisted even after controlling for other psychiatric disorders and substance involvement. Overlapping genetic (rG = 0.45) and environmental (rE = 0.21) factors were responsible for the covariance between cannabis involvement and SI. Conclusions Cannabis involvement is associated, albeit modestly, with SI and unplanned suicide attempts. Such attempts are difficult to prevent and their association with cannabis use and cannabis use disorder symptoms requires further study, including in different samples and with additional attention to confounders. Keywords Suicidal thoughts and behaviors; Cannabis use; Cannabis use disorder symptom

Towards Water Quality Models [and Discussion]

Predictions of water quality involve the modelling both of physical processes, which underlie the transport and diffusion of all constituents, and of the sources, sinks, partitioning and interactive processes individual to those constituents. These processes are outlined, together with complementary modelling approaches: (i) development of sophisticated three-dimensional models to represent the physics, and sub-models of suspended sediment, microbiology and metal interactions for processes controlling nutrients, dissolved oxygen, phytoplankton, detritus and metals; (ii) a framework to link these component models; (iii) an accessible model with simpler physics for wide use in simulating constituent distributions, for comparison with measurements to infer sources, sinks and interactions. The North Sea Project measurements provide an input in process evaluation, and data to test the models