Cannabis and Depression: A Twin Model Approach to Co-morbidity.

Cannabis use disorder (CUD) co-occurs with major depressive disorder (MDD) more frequently than would be expected by chance. However, studies to date have not produced a clear understanding of the mechanisms underlying this co-morbidity. Genetically informative studies can add valuable insight to this problem, as they allow the evaluation of competing models of co-morbidity. This study uses data from the Australian Twin Registry to compare 13 co-morbidity twin models initially proposed by Neale and Kendler (Am J Hum Genet 57:935-953, 1995). The analysis sample comprised 2410 male and female monozygotic and dizygotic twins (average age 32) who were assessed on CUD and MDD using the SSAGA-OZ interview. Data were analyzed in OpenMx. Of the 13 different co-morbidity models, two fit equally well: CUD causes MDD and Random Multiformity of CUD. Both fit substantially better than the Correlated Liabilities model. Although the current study cannot differentiate between them statistically, these models, in combination, suggest that CUD risk factors may causally influence the risk to develop MDD, but only when risk for CUD is high.

Consumer and carer perspectives in the development of a mental health research, treatment and teaching facility: A thematic analysis.

WHAT IS KNOWN ON THE SUBJECT?: Around the world, recovery has become a focus in mental health policy. The participation of people accessing mental health services (consumers) and carers of such individuals in decision-making related to services forms part of this recovery orientation and studies suggest positive outcomes following such participation. However, little is known about consumer and carer desires at the earliest stages of development of new services. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Consumers and carers desire changes to how mental health services are provided. Many factors affect consumer and carer experiences, including language use, physical design of spaces, accessibility, consideration of individual needs, practical help and how well care is continued from hospital to community settings. Carers may feel sidelined in treatment and be distressed as a result. They wish to be respected and involved in recovery. Consumers and carers wish for focus on broader health, with care taken to address physical health, psychological needs, social needs and treatment of the whole person rather than just an illness. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Consumers and carers desire partnership with professionals in recovery. Tokenistic participation should be avoided. Flexibility in how services are provided and less formality may help engage consumers and carers. Specifically, professionals may help by linking consumers and carers to services that address practical needs. Professionals should communicate with carers to draw on their expertise about the individual accessing the mental health service and help carers understand how they can assist the individual's recovery. ABSTRACT: Introduction Recovery-oriented mental health policies recognize consumer and carer participation in service decision-making as essential, but little is known about the views of these individuals in the earliest stages of service development. Aim This study sought consumer and carer perspectives addressing the establishment of a mental health research, treatment and teaching facility in their region. Methods Two 2-hr focus groups were conducted, with separate groups held for mental health consumers (n = 9) and carers (n = 9), respectively. Discussions pertained to mental health literacy, gaps in current services, desires for an ideal facility (in terms of physical design and services offered) and what would help in recovery. Results Inductive thematic analysis was used to generate three themes: care outside of consultations, carer involvement in recovery and holistic approaches to mental health care. Consumers desired a facility that could cater to individual needs. Carers felt excluded in recovery and unable to provide effective support. Both groups preferred holistic approaches to mental health, expressing ambivalence towards medication and hospitalization. Discussion Consumers and carers have many needs that conventional practices may not meet. Implications for practice They have clear desires for equal partnership in recovery and for transformation of conventional treatment methods.

Most of the genetic covariation between major depressive and alcohol use disorders is explained by trait measures of negative emotionality and behavioral control.

BACKGROUND: Mental health disorders commonly co-occur, even between conceptually distinct syndromes, such as internalizing and externalizing disorders. The current study investigated whether phenotypic, genetic, and environmental variance in negative emotionality and behavioral control account for the covariation between major depressive disorder (MDD) and alcohol use disorder (AUD). METHOD: A total of 3623 members of a national twin registry were administered structured diagnostic telephone interviews that included assessments of lifetime histories of MDD and AUD, and were mailed self-report personality questionnaires that assessed stress reactivity (SR) and behavioral control (CON). A series of biometric models were fitted to partition the proportion of covariance between MDD and AUD into SR and CON. RESULTS: A statistically significant proportion of the correlation between MDD and AUD was due to variance specific to SR (men = 0.31, women = 0.27) and CON (men = 0.20, women = 0.19). Further, genetic factors explained a large proportion of this correlation (0.63), with unique environmental factors explaining the rest. SR explained a significant proportion of the genetic (0.33) and environmental (0.23) overlap between MDD and AUD. In contrast, variance specific to CON accounted for genetic overlap (0.32), but not environmental overlap (0.004). In total, SR and CON accounted for approximately 70% of the genetic and 20% of the environmental covariation between MDD and AUD. CONCLUSIONS: This is the first study to demonstrate that negative emotionality and behavioral control confer risk for the co-occurrence of MDD and AUD via genetic factors. These findings are consistent with the aims of NIMH's RDoC proposal to elucidate how transdiagnostic risk factors drive psychopathology.

The association between childhood maltreatment, psychopathology, and adult sexual victimization in men and women: results from three independent samples.

BACKGROUND: Childhood maltreatment (CM) has consistently been linked with adverse outcomes including substance use disorders and adult sexual revictimization. Adult sexual victimization itself has been linked with psychopathology but has predominately been studied in women. The current investigation examines the impact of CM and co-occurring psychopathology on adult sexual victimization in men and women, replicating findings in three distinct samples. METHOD: We investigated the association between continuous CM factor scores and adult sexual victimization in the Childhood Trauma Study (CTS) sample (N = 2564). We also examined the unique relationship between childhood sexual abuse (CSA) and adult sexual victimization while adjusting for co-occurring substance dependence and psychopathology. We replicated these analyses in two additional samples: the Comorbidity and Trauma Study (CATS; N = 1981) and the Australian Twin-Family Study of Alcohol Use Disorders (OZ-ALC; N = 1537). RESULTS: Analyses revealed a significant association with CM factor scores and adult sexual victimization for both men and women across all three samples. The CSA factor score was strongly associated with adult sexual victimization after adjusting for substance dependence and psychopathology; higher odds ratios were observed in men (than women) consistently across the three samples. CONCLUSIONS: A continuous measure of CSA is independently associated with adult sexual trauma risk across samples in models that included commonly associated substance dependence and psychopathology as covariates. The strength of the association between this CSA measure and adult sexual victimization is higher in magnitude for men than women, pointing to the need for further investigation of sexual victimization in male community samples.

The role of conduct disorder in the relationship between alcohol, nicotine and cannabis use disorders.

BACKGROUND: Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses. METHOD: Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24-37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder. RESULTS: Additive genetic (a(2) = 0.48-0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a(2) = 0.39) and shared environmental (c(2) = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38-0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40-73% of the genetic variance per substance. CONCLUSIONS: Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.

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<0.01). Cannabis use and endorsing ≥3 symptoms were associated with unplanned (SANP; ORs=1.95 and 2.51 respectively, p<0.05), but not planned suicide attempts (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.

Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned.

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.

Parental depression and offspring psychopathology: a children of twins study.

BACKGROUND: Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations. METHOD: A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds. RESULTS: In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20-1.93] and conduct disorder (CD; HR 2.27, CI 1.31-3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00-1.94). Logistic regression analysis suggested that the parental depression-offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63-3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95-6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses. CONCLUSIONS: The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.

Genetic and environmental contributions to cannabis dependence in a national young adult twin sample.

BACKGROUND: This paper examines genetic and environmental contributions to risk of cannabis dependence. METHOD: Symptoms of cannabis dependence and measures of social, family and individual risk factors were assessed in a sample of 6265 young adult male and female Australian twins born 1964-1971. RESULTS: Symptoms of cannabis dependence were common: 11.0% of sample (15.1% of men and 7.8% of women) reported two or more symptoms of dependence. Correlates of cannabis dependence included educational attainment, exposure to parental conflict, sexual abuse, major depression, social anxiety and childhood conduct disorder. However, even after control for the effects of these factors, there was evidence of significant genetic effects on risk of cannabis dependence. Standard genetic modelling indicated that 44.7% (95% CI = 15-72.2) of the variance in liability to cannabis dependence could be accounted for by genetic factors, 20.1% (95% CI = 0-43.6) could be attributed to shared environment factors and 35.3% (95% CI = 26.4-45.7) could be attributed to non-shared environmental factors. However, while there was no evidence of significant gender differences in the magnitude of genetic and environmental influences, a model which assumed both genetic and shared environmental influences on risks of cannabis dependence among men and shared environmental but no genetic influences among women provided an equally good fit to the data. CONCLUSIONS: There was consistent evidence that genetic risk factors are important determinants of risk of cannabis dependence among men. However, it remains uncertain whether there are genetic influences on liability to cannabis dependence among women.

Predictors of non-response to a questionnaire survey of a volunteer twin panel: findings from the Australian 1989 twin cohort.

Questionnaire surveys, while more economical, typically achieve poorer response rates than interview surveys. We used data from a national volunteer cohort of young adult twins, who were scheduled for assessment by questionnaire in 1989 and by interview in 1996-2000, to identify predictors of questionnaire non-response. Out of a total of 8536 twins, 5058 completed the questionnaire survey (59% response rate), and 6255 completed a telephone interview survey conducted a decade later (73% response rate). Multinomial logit models were fitted to the interview data to identify socioeconomic, psychiatric and health behavior correlates of non-response in the earlier questionnaire survey. Male gender, education below University level, and being a dizygotic rather than monozygotic twin, all predicted reduced likelihood of participating in the questionnaire survey. Associations between questionnaire response status and psychiatric history and health behavior variables were modest, with history of alcohol dependence and childhood conduct disorder predicting decreased probability of returning a questionnaire, and history of smoking and heavy drinking more weakly associated with non-response. Body-mass index showed no association with questionnaire non-response. Despite a poor response rate to the self-report questionnaire survey, we found only limited sampling biases for most variables. While not appropriate for studies where socioeconomic variables are critical, it appears that survey by questionnaire, with questionnaire administration by telephone to non-responders, will represent a viable strategy for gene-mapping studies requiring that large numbers of relatives be screened.

Towards a molecular epidemiology of alcohol dependence: analysing the interplay of genetic and environmental risk factors.

BACKGROUND: Progress in identifying genetic factors protective against alcohol dependence (AlcD) requires a paradigm shift in psychiatric epidemiology. AIMS: To integrate analysis of research into the genetics of alcoholism. METHOD: Data from prospective questionnaire and interview surveys of the Australian twin panel, and from a subsample who underwent alcohol challenge, were analysed. RESULTS: In men, effects of alcohol dehydrogenase ADH2*1/*2 genotype or high alcohol sensitivity (risk-decreasing), and of history of childhood conduct disorder, or having monozygotic co-twin or twin sister with AlcD (risk-increasing) were significant and comparable in magnitude. Religious affiliation (Anglican versus other) was associated with the ADH2 genotype, but did not explain the associations with AlcD symptoms. No protective effect of the ADH2*1/*2 genotype was observed in women. CONCLUSIONS: The early onset and strong familial aggregation of AlcD, and opportunity for within-family tests of genetic association to avoid confounding effects, make epidemiological family studies of adolescents and young adults and their families a priority.

Childhood sexual abuse and pathogenic parenting in the childhood recollections of adult twin pairs.

BACKGROUND: We examined the relationship between childhood sexual abuse (CSA), and interviewees' recollections of pathogenic parenting, testing for possible retrospective biases in the recollections of those who have experienced CSA. METHODS: Information about CSA, parental divorce and interviewees' recollections of parental rejection, parental overprotection and perceived autonomy (as assessed through a shortened version of the Parental Bonding Instrument) was obtained through telephone interviews with 3626 Australian twins who had also returned self-report questionnaires several years earlier. Recollections of parental behaviours were compared for individuals from pairs in which neither twin, at least one twin, or both twins reported CSA. RESULTS: Significant associations were noted between CSA and paternal alcoholism and between CSA and recollections of parental rejection. For women, individuals from CSA-discordant pairs reported levels of parental rejection that were significantly higher than those obtained from CSA-negative pairs. The levels of parental rejection observed for twins from CSA-discordant pairs did not differ significantly from those obtained from CSA-concordant pairs, regardless of respondent's abuse status. For men from CSA-discordant pairs, respondents reporting CSA displayed a tendency to report higher levels of parental rejection than did respondents not reporting CSA. Other measures of parenting behaviour (perceived autonomy and parental overprotection) failed to show a clear relationship with CSA. CONCLUSIONS: The relationship between CSA and respondents' recollections of parental rejection is not due solely to retrospective bias on the part of abused individuals and, consistent with other studies, may reflect a pathological family environment with serious consequences for all siblings.

Monoamine oxidase: associations with alcohol dependence, smoking and other measures of psychopathology.

BACKGROUND: Many reports have appeared on associations between platelet monoamine oxidase (MAO) activity and susceptibility to psychiatric conditions; principally alcohol dependence but also conduct disorder, other drug use and depression. Recently, it has become apparent that MAO activity is inhibited by some component of cigarette smoke, and smokers have low platelet MAO activity. Since the prevalence of smoking is higher in many of the conditions in which MAO has been implicated, the MAO susceptibility associations may be partly, or entirely, false. METHODS: We have measured platelet MAO in 1551 subjects, recruited from the Australian NHMRC Twin Registry, who have provided information on alcohol use and dependence, smoking, conduct disorder, depression, attempted suicide, panic disorder and social phobia. RESULTS: Current smoking reduced platelet MAO activity in a significant and dose-related manner, with no evidence of lower MAO in ex-smokers or in non-smoking subjects with co-twins who smoked. Alcohol use and lifetime DSM-III-R alcohol dependence history were not associated with MAO activity when smoking was taken into account. Depression, panic disorder and social phobia showed no significant associations with platelet MAO activity. Subjects with a history of serious attempts at suicide had low platelet MAO activity; but although the difference from controls was as great as the reduction associated with smoking it was not significant after correction for smoking effects. CONCLUSIONS: Although synaptic MAO activity undoubtedly plays a role in psychopathology, the concept that platelet MAO activity is a direct genetic marker of vulnerability to alcohol dependence cannot be sustained.

Early sexual abuse and lifetime psychopathology: a co-twin-control study.

BACKGROUND: This study was designed to determine lifetime prevalence of psychiatric disorders among twins who reported childhood sexual abuse (CSA), and to compare these rates with those among non-abused co-twins. The contribution of familial and individual-specific factors to reported sexual abuse was also examined. METHOD: Information about lifetime psychopathology and substance use was obtained by structured telephone interviews with 5995 Australian twins. Twins who reported a history of childhood sexual abuse (CSA) were contrasted on lifetime psychopathology with subjects without such a history; in addition, comparisons were made between same-sex twin pairs discordant for CSA. RESULTS: A history of CSA was reported by 5.9% of the women and 2.5% of the men. In the sample as a whole, those reporting CSA were more likely to receive lifetime diagnoses of major depression, conduct disorder, panic disorder and alcoholism, and were more likely to report suicidal ideation and a history of suicide attempt. Abused women, but not men, were also more likely to report social phobia. When comparisons were restricted to non-abused co-twins, no differences in psychopathology were seen. However, rates of major depression, conduct disorder and suicidal ideation were higher if both co-twins were abused than if the respondent alone reported CSA. Model-fitting indicated that shared environmental factors influenced risk for reported CSA in women, but not in men. CONCLUSION: The association between CSA and psychopathology arises at least in part through the influence of shared familial factors on both risk of victimization and risk of psychopathology.

A study of the genetic and environmental etiology of stuttering in a selected twin sample.

Stuttering is a developmental disorder of speech production that usually emerges in childhood. In this study, a large population-based twin sample from the Australian Twin Registry (1567 pairs and 634 singles aged 17-29 years) was screened to identify twin pairs in which one or both members reported themselves to be affected by stuttering. Telephone interview-based diagnoses were obtained for 457 of these individuals (self-reported affected cases, cotwins, and controls) to determine whether the self-report was correct. To correct for ascertainment bias we carried out a bivariate analysis of the final diagnosis in the selected sample with the screening item in the full sample, using the categorical raw data option of Mx 1.47c. After correcting for ascertainment bias, approximately 70% (95% confidence interval: 39-86%) of the variance in liability to stuttering was found to be attributable to additive genetic effects, with the remainder due to nonshared environmental effects.

Anxiety and depression in twin and sib pairs extremely discordant and concordant for neuroticism: prodromus to a linkage study.

Multivariate modelling of anxiety and depression data in twins has suggested that the two phenotypes are largely underpinned by one genetic factor, while other studies have indicated a relationship between these disorders and the neuroticism personality trait. As part of a study to identify quantitative trait loci for anxiety and depression, questionnaire responses and interviews of 15,027 Australian twins and 11,389 of their family members conducted during the past 20 years were reviewed to identify individuals with neuroticism, anxiety and depression scores in the upper or lower deciles of the population. This information was then used to identify extreme discordant and concordant (EDAC) sib pairs. 1373 high-scoring and 1571 low-scoring subjects (2357 sib pairs) were selected for participation, and extremely high participation rates were achieved, with over 90% of contactable prospective participants completing the interview phase, and over 90% of these providing blood or buccal samples. Participation bias arising from the nature of the selection variables was minimal, with only a small difference between rates of interview participation among prospective participants with high and low selection scores (89.4% vs 91.6%). The interview permitted the diagnosis of depression and several anxiety disorders (OCD, agoraphobia, panic disorder, generalised anxiety disorder) in this sample according to DSM-IV criteria. The methodology for selection of prospective subjects was demonstrated to be extremely successful, with highly significant differences in depression and anxiety disorder prevalence rates between individuals in the two selection groups. The success of this EDAC sampling scheme will enhance the power for QTL linkage and association analysis in this sample.

Genetic differences in alcohol sensitivity and the inheritance of alcoholism risk.

BACKGROUND: Substantial evidence exists for an important genetic contribution to alcohol dependence risk in women and men. It has been suggested that genetically determined differences in alcohol sensitivity may represent one pathway by which an increase in alcohol dependence risk occurs. METHODS: Telephone interview follow-up data were obtained on twins from male, female and unlike-sex twin pairs who had participated in an alcohol challenge study in 1979-81, as well as other pairs from the same Australian twin panel surveyed by mail in 1980-82. RESULTS: At follow-up, alcohol challenge men did not differ from other male twins from the same age cohort on measures of lifetime psychopathology or drinking habits; but alcohol challenge omen were on average heavier drinkers than other women. A composite alcohol sensitivity measure, combining subjective intoxication and increase in body-sway after alcohol challenge in 1979-81, exhibited high heritability (60 %). Parental alcoholism history was weakly associated with decreased alcohol sensitivity in women, but not after adjustment for baseline drinking history, or in men. High alcohol sensitivity in men was associated with substantially reduced alcohol dependence risk (OR = 0.05, 95% CI 0.01-0.39). Furthermore, significantly decreased (i.e. low) alcohol sensitivity was observed in non-alcoholic males whose MZ co-twin had a history of alcohol dependence, compared to other non-alcoholics. These associations remained significant in conservative analyses that controlled for respondents' alcohol consumption levels and alcohol problems in 1979-81. CONCLUSIONS: Men (but not women) at increased genetic risk of alcohol dependence (assessed by MZ co-twin's history of alcohol dependence) exhibited reduced alcohol sensitivity. Associations with parental alcoholism were inconsistent.

Major depressive disorder in a community-based twin sample: are there different genetic and environmental contributions for men and women?

BACKGROUND: Depression affects more women than men and often aggregates in families. Using a community-based sample of twins, we examined the contributions of genetic and environmental factors to the risk of developing major depressive disorder and the effect of sex and different definitions of depression on the relative contributions of genetic and environmental effects. Sex differences in genetic effects were also studied. METHODS: A volunteer sample of Australian twins (2662 pairs) was interviewed using an abbreviated version of the Semi-Structured Assessment for the Genetics of Alcoholism, a semi-structured lay interview designed to assess psychiatric disorders. Depression was defined using 3 different criteria sets: DSM-III-R major depressive disorder, DSM-IV major depressive disorder, and severe DSM-IV major depressive disorder. Genetic and environmental contributions to the liability to develop depression were estimated using genetic model fitting. RESULTS: Lifetime prevalences were 31% in women and 24% in men for DSM-III-R major depressive disorder, 22% in women and 16% in men for DSM-IV major depressive disorder, and 9% in women and 3% in men for severe DSM-IV major depressive disorder. In women, the simplest model to fit the data implicated genetic factors and environmental factors unique to the individual in the development of depression, with heritability estimates ranging from 36% to 44%. In men, depression was only modestly familial, and thus individual environmental factors played a larger role in the development of depression. For DSM-III-R major depressive disorder, there were statistically different estimates for heritability for men vs. women. For both sexes, the relative contributions of genetic and environmental factors were stable using different definitions of depression. CONCLUSIONS: There was moderate familial aggregation of depression in women and this primarily was attributable to genetic factors. In men, there was only modest familial aggregation of depression. For both men and women, individual environmental experiences played a large role in the development of depression. Major depressive disorder as defined by DSM-III-R was more heritable in women as compared with men. The relative contributions of genetic and environmental factors in the development of depression were similar for varying definitions of depression, from a broad definition to a narrow definition.

Suicidal behaviour: an epidemiological and genetic study.

BACKGROUND: Psychiatric history, familial history of suicide attempts, and certain traumatic life events are important predictors of suicidal thoughts and behaviour. We examined the epidemiology and genetics of suicidality (i.e. reporting persistent suicidal thoughts or a plan or suicide attempt) in a large community-based sample of MZ and DZ twin pairs. METHOD: Diagnostic telephone interviews were conducted in 1992-3 with twins from an Australian twin panel first surveyed in 1980-82 (N = 5995 respondents). Data were analysed using logistic regression models, taking into account twin pair zygosity and the history of suicidality in the respondent's co-twin. RESULTS: Lifetime prevalence of suicidal thoughts and attempts was remarkably constant across birth cohorts 1930-1964, and across gender. Major psychiatric correlates were history of major depression, panic disorder, social phobia in women, alcohol dependence and childhood conduct problems. Traumatic events involving assault (childhood sexual abuse, rape or physical assault) or status-loss (job loss, loss of property or home, divorce), and the personality trait neuroticism, were also significantly associated with suicide measures. Prevalence of serious suicide attempts varied as a function of religious affiliation. After controlling for these variables, however, history of suicide attempts or persistent thoughts in the respondent's co-twin remained a powerful predictor in MZ pairs (odds ratio = 3.9), but was not consistently predictive in DZ pairs. Overall, genetic factors accounted for approximately 45% of the variance in suicidal thoughts and behaviour (95% confidence interval 33-51%). CONCLUSIONS: Risk of persistent suicidal thoughts and suicide attempts is determined by a complex interplay of psychiatric history, neuroticism, traumatic life experiences, genetic vulnerability specific for suicidal behaviour and sociocultural risk or protective factors.

Common genetic risk factors for conduct disorder and alcohol dependence.

The association between retrospectively reported childhood conduct disorder (CD) and a history of alcohol dependence (AD) was examined in a sample of 2,682 male, female, and unlike-sex adult twin pairs. There was a strong association between CD and AD in both men (tetrachoric r = .34, odds ratio = 2.8) and women (tetrachoric r = .53, odds ratio = 9.9). Genetic factors accounted for most of the association between CD and AD liability in men and women, with the remainder of the association being due to nonshared individual-specific environmental factors. Genetic influences common to CD and AD accounted for 17% and 35% of the genetic variation in AD liability in men and women, respectively, and accounted for 11% and 23% of the total variation in AD liability in men and women, respectively. The results suggest that there are common genetic risk factors for CD and AD or that CD itself is an important genetically influenced risk factor for AD.