Marriage and reductions in men's alcohol, tobacco, and cannabis use.

BACKGROUND: Psychoactive substance use is lower among married compared to divorced or unmarried men; yet, the nature of this effect remains unclear because becoming and staying married is potentially confounded with substance-related background familial and individual factors, like parental divorce and personality. The authors investigated the associations between marital status and substance use; how substance use changed across the transition to marriage; and whether marriage effects were likely to be causal. METHOD: The sample included 1790 adults from male-male twin pairs from a population-based registry. Measures of marital status and alcohol, tobacco, and cannabis use came from Life History Calendars. Data were analyzed using regression, co-twin comparison, and within-person models. The latter models are tools for quasi-causal inference that control for familial and individual-level confounders. RESULTS: Married men used less alcohol, tobacco, and cannabis than men who were divorced/separated or single. In analyses of substance use across the transition to marriage, men reduced their alcohol and cannabis use both before and after marriage, but their tobacco use only after marriage. These effects were largely robust in co-twin and within-person analyses. CONCLUSIONS: Marriage was associated with substantial reductions in substance use compared to being divorced/separated or single, and these reductions began prior to marriage. The co-twin comparison and within-person models ruled out the alternative explanation that marriage effects were due to confounding background familial and individual factors. These results provide strong evidence that the social role expectations associated with marriage reduce psychoactive substance use.

Shared and specific genetic risk factors for lifetime major depression, depressive symptoms and neuroticism in three population-based twin samples.

BACKGROUND: Vulnerability to depression can be measured in different ways. We here examine how genetic risk factors are inter-related for lifetime major depression (MD), self-report current depressive symptoms and the personality trait Neuroticism. METHOD: We obtained data from three population-based adult twin samples (Virginia n = 4672, Australia #1 n = 3598 and Australia #2 n = 1878) to which we fitted a common factor model where risk for 'broadly defined depression' was indexed by (i) lifetime MD assessed at personal interview, (ii) depressive symptoms, and (iii) neuroticism. We examined the proportion of genetic risk for MD deriving from the common factor v. specific to MD in each sample and then analyzed them jointly. Structural equation modeling was conducted in Mx. RESULTS: The best fit models in all samples included additive genetic and unique environmental effects. The proportion of genetic effects unique to lifetime MD and not shared with the broad depression common factor in the three samples were estimated as 77, 61, and 65%, respectively. A cross-sample mega-analysis model fit well and estimated that 65% of the genetic risk for MD was unique. CONCLUSION: A large proportion of genetic risk factors for lifetime MD was not, in the samples studied, captured by a common factor for broadly defined depression utilizing MD and self-report measures of current depressive symptoms and Neuroticism. The genetic substrate for MD may reflect neurobiological processes underlying the episodic nature of its cognitive, motor and neurovegetative manifestations, which are not well indexed by current depressive symptom and neuroticism.

Time course of panic disorder and posttraumatic stress disorder onsets.

PURPOSE: Posttraumatic stress disorder (PTSD) often co-occurs with panic disorder (PD), with some etiological models positing a causal role of panic reactivity in PTSD onset; however, data addressing the temporal ordering of these conditions are lacking. The aim of this study was to examine the bi-directional associations between PD and PTSD in a nationally representative, epidemiologic sample of trauma-exposed adults. METHODS: Participants were community-dwelling adults (62.6% women; Mage = 48.9, SD 16.3) with lifetime DSM-IV PTSD criterion A trauma exposure drawn from the 2001/2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and re-interviewed in 2004/5 (N = 12,467). Cox discrete-time proportional hazards models with time-varying covariates were used to investigate the bi-directional associations between lifetime PD and PTSD, accounting for demographic characteristics, trauma load, and lifetime history of major depression, generalized anxiety disorder, and social anxiety disorder. RESULTS: PD was significantly associated with subsequent onset of PTSD (HR 1.210, 95%CI = 1.207-1.214, p < .001), and PTSD was significantly associated with onset of PD (HR 1.601, 95% CI 1.597-1.604, p < .001). The association between PTSD and subsequent PD was stronger in magnitude than that between PD and subsequent PTSD (Z = - 275.21, p < .01). Men evidenced stronger associations between PD and PTSD compared to women. CONCLUSIONS: Results were consistent with a bidirectional pathway of risk, whereby PD significantly increased risk for the development of PTSD, and PTSD significantly increased risk for PD. Given the association between PTSD and subsequent PD, particularly among men, clinicians may consider supplementing PTSD treatment with panic-specific interventions, such as interoceptive exposure, to prevent or treat this disabling comorbidity.

Sex similarities and differences in risk factors for recurrence of major depression.

BACKGROUND: Major depression (MD) occurs about twice as often in women as in men, but it is unclear whether sex differences subsist after disease onset. This study aims to elucidate potential sex differences in rates and risk factors for MD recurrence, in order to improve prediction of course of illness and understanding of its underlying mechanisms. METHODS: We used prospective data from a general population sample (n = 653) that experienced a recent episode of MD. A diverse set of potential risk factors for recurrence of MD was analyzed using Cox models subject to elastic net regularization for males and females separately. Accuracy of the prediction models was tested in same-sex and opposite-sex test data. Additionally, interactions between sex and each of the risk factors were investigated to identify potential sex differences. RESULTS: Recurrence rates and the impact of most risk factors were similar for men and women. For both sexes, prediction models were highly multifactorial including risk factors such as comorbid anxiety, early traumas, and family history. Some subtle sex differences were detected: for men, prediction models included more risk factors concerning characteristics of the depressive episode and family history of MD and generalized anxiety, whereas for women, models included more risk factors concerning early and recent adverse life events and socioeconomic problems. CONCLUSIONS: No prominent sex differences in risk factors for recurrence of MD were found, potentially indicating similar disease maintaining mechanisms for both sexes. Course of MD is a multifactorial phenomenon for both males and females.

The impact of resilience and subsequent stressful life events on MDD and GAD.

BACKGROUND: There remains a dearth of research examining the "buffering" effect of resilience, wherein resilience at one point in time would be expected to protect an individual against development of psychopathology following future adverse life events. METHODS: Using longitudinal data from an epidemiological twin sample (N = 7463), this study tested whether resilience would act as a buffer for stressful life events (SLEs) against risk for major depressive disorder (MDD) and generalized anxiety disorder (GAD). Resilience, demographics, and psychopathology were measured at Time 1 and recent SLEs and current MDD and GAD were measured at Time 2. RESULTS: Final models, controlling for demographic covariates and Time 1 diagnosis, examined the impact of Time 1 resilience, recent SLEs, their interaction, and a three-way interaction adding sex on MDD and GAD. CONCLUSIONS: The pattern of findings was the same for MDD and GAD, wherein main effects and two-way interactions of resilience and SLEs were significant, such that greater resilience was protective even in the context of high numbers of past-year SLEs. The three-way interaction was not significant, suggesting that the relationship between SLEs and resilience on psychopathology was the same for both men and women. Findings support the conceptualization of resilience as a buffer against the impact of future life stressors on common internalizing psychopathology. Longitudinal designs and trajectory-based studies that include recurring measures of SLEs could inform conceptualizations of resilience in the context of ongoing adversity and aid in developing interventions aimed at fostering healthy adaptation in the face of stressors.

Sex differences in the pathways to symptoms of alcohol use disorder: a study of opposite-sex twin pairs.

BACKGROUND: We sought to develop an empirical, broad-based developmental model for sex differences in risk for symptoms of alcohol use disorders, here called alcohol problems (APs). METHODS: We assessed 18 risk factors in 5 developmental tiers in both members of 1,377 opposite-sex dizygotic twin pairs from the Virginia population-based twin registry. Analyses were conducted by structural modeling, examining within-pair differences. RESULTS: The best-fitting model explained 73% of the variance in men and 71% in women for last year AP. Forty-nine percent of paths differed significantly across sexes. Ten variables had appreciably different predictive effects on AP in males versus females. Three were stronger in females: familial risk, early-onset anxiety disorders, and nicotine dependence. Seven predictors had a stronger total effect in males: novelty seeking, conduct disorder, childhood sexual abuse, parental loss, neuroticism, low self-esteem, and low marital satisfaction. CONCLUSIONS: In a co-twin control design, which matches sisters and brothers on genetic and familial-environmental background, we found numerous sex differences in predictors of last year AP. Factors that were more prominent in men and in women were diverse, reflecting both internalizing and externalizing psychopathology. The model was slightly more successful at predicting AP in men than in women.

Dimensions of parental alcohol use/problems and offspring temperament, externalizing behaviors, and alcohol use/problems.

BACKGROUND: Alcohol consumption (AC) and alcohol problems (AP) are complex traits. How many factors reflecting parental AC and AP are present in the large prospectively followed Avon Longitudinal Study of Parents and Children cohort? Would these factors be uniquely associated with various temperamental and alcohol-related outcomes in the children? METHODS: We factor-analyzed multiple items reflecting maternal and paternal AC and AP measured over a 12-year period from before the birth of the child (n = 14,093 families). We examined, by linear regression controlling for socioeconomic status, the relationship between scales derived from these factors and offspring early childhood temperament, externalizing traits, and adolescent AC and AP (ns ranging from 9,732 to 3,454). RESULTS: We identified 5 coherent factors: typical maternal AC, maternal AC during pregnancy, maternal AP, paternal AC, and paternal AP. In univariate analyses, maternal and paternal AC and AP were modestly and significantly associated with low shyness, sociability, hyperactivity, and conduct problems in childhood and early adolescence; delinquent behavior at age 15; and AC and AP at ages 15 and 18. AC and AP at age 18 were more strongly predicted by parental factors than at age 15. Maternal AC during pregnancy uniquely predicted externalizing traits at ages 4, 13, and 15. CONCLUSIONS: Parental AC and AP are complex multidimensional traits that differ in their association with a range of relevant measures in their children. Controlling for background AC and AP, self-reported levels of maternal AC during pregnancy uniquely predicted externalizing behaviors in childhood and adolescence.

Parenting and risk for mood, anxiety and substance use disorders: a study in population-based male twins.

BACKGROUND: Previous studies consistently identified a relationship between parenting behavior and psychopathology. In this study, we extended prior analyses performed in female twins to a large sample of twins from male-male pairs. METHODS: We used interview data on 2,609 adult male twins from a population-based twin registry. We examined the association between three retrospectively reported parenting dimensions (coldness, protectiveness, and authoritarianism) and lifetime history of seven common psychiatric and substance use disorders. Using univariate structural equation modeling, we also examined the influence of the genetic and environmental factors on parenting. RESULTS: Examined individually, coldness was consistently associated with risk for a broad range of adult psychopathology. Averaged odds of psychiatric disorders associated with parenting were increased between 26 and 36 %. When the three parenting dimensions were examined together, coldness remained significant for major depression, phobia, and generalized anxiety disorder. Controlling for other disorders, the associations between the parenting dimensions and psychopathology were non-specific. Twin fitting model demonstrated that modest heritability accounted for parenting, whereas most variance resulted from the non-shared environment. CONCLUSIONS: Based on our current and prior findings, there is broad similarity in the impact of parenting on adult psychopathology between men and women.

The impact of environmental experiences on symptoms of anxiety and depression across the life span.

Symptoms of anxiety and depression are relatively stable over time. Can this stability be explained by genetic influences, or is it caused by the long-lasting effects of accumulating environmental experiences? To address this question, we analyzed longitudinally assessed symptoms of anxiety and depression in eight samples of monozygotic twins of widely varying ages. These samples were drawn from American and European population-based registries. Using hierarchical linear modeling, we examined individual differences and individual changes in the level of symptoms over time. This method enabled us to decompose the variance into the predictable variance shared by both members of each pair of twins, the differences between individuals within pairs, and the residual variance. We then modeled how these components of individual variation changed over time. Within pairs, the twins' predicted levels of symptoms increasingly diverged from childhood until late adulthood, at which point the divergence ceased. By middle adulthood, environmental experiences contributed substantially to stable and predictable interindividual differences in levels of anxiety and depression.

Toward a comprehensive developmental model for alcohol use disorders in men.

The multiple risk factors for alcohol use (AU) and alcohol use disorders (AUDs) are interrelated through poorly understood pathways, many of which begin in childhood. In this report, the authors seek to develop an empirical, broad-based developmental model for the etiology of AU and AUDs in men. We assessed 15 risk factors in four developmental tiers in 1,794 adult male twins from the Virginia population based twin registry. The best fitting model explained 39% of the variance in late adolescent AU, and 30% of the liability to lifetime symptoms of AUD. AU and AUDs can be best understood as arising from the action and interaction of two pathways reflecting externalizing genetic/temperamental and familial/social factors. Peer group deviance was important in each pathway. Internalizing symptoms played a more minor role. Familial/social factors were especially important influences on AU, while genetic/temperamental factors were more critical for AUDs. We conclude that AU and AUDs in men are complex traits influenced by genetic, family, temperamental, and social factors, acting and interacting over developmental time.

Interpretation of interactions: guide for the perplexed.

In this issue, Zammit et al explore how five dichotomised risk factors work together to predict risk for non-affective psychosis in a large Swedish cohort. In this editorial, we review these findings, and comment on both the nature of additive v. multiplicative models and the meaning of statistical interactions.

Creating a social world: a developmental twin study of peer-group deviance.

CONTEXT: Peer-group deviance is strongly associated with externalizing behaviors. We have limited knowledge of the sources of individual differences in peer-group deviance. OBJECTIVE: To clarify genetic and environmental contributions to peer-group deviance in twins from midchildhood through early adulthood. DESIGN: Retrospective assessments using a life-history calendar. Analysis by biometric growth curves. SETTING: General community. PARTICIPANTS: Members of male-male pairs from the population-based Virginia Twin Registry personally interviewed in 1998-2004 (n = 1802). MAIN OUTCOME MEASURE: Self-reported peer-group deviance at ages 8 to 11, 12 to 14, 15 to 17, 18 to 21, and 22 to 25 years. RESULTS: Mean and variance of peer-group deviance increased substantially with age. Genetic effects on peer-group deviance showed a strong and steady increase over time. Family environment generally declined in importance over time. Individual-specific environmental influences on peer-group deviance levels were stable in the first 3 age periods and then increased as most twins left home. When standardized, the heritability of peer-group deviance is approximately 30% at ages 8 to 11 years and rises to approximately 50% across the last 3 time periods. Both genes and shared environment contributed to individual differences in the developmental trajectory of peer-group deviance. However, while the correlation between childhood peer-group deviance levels and the subsequent slope of peer-group deviance over time resulting from genetic factors was positive, the same relationship resulting from shared environmental factors was negative. CONCLUSIONS: As male twins mature and create their own social worlds, genetic factors play an increasingly important role in their choice of peers, while shared environment becomes less influential. The individual-specific environment increases in importance when individuals leave home. Individuals who have deviant peers in childhood, as a result of genetic vs shared environmental influences, have distinct developmental trajectories. Understanding the risk factors for peer-group deviance will help clarify the etiology of a range of externalizing psychopathology.

Socioeconomic status and social support following illicit drug use: causal pathways or common liability?

The negative social attributes associated with drug use and abuse/dependence may arise as a result of shared genetic or environmental factors rather than through causal pathways. To evaluate this possibility, structured interviews were conducted for 3969 male and female twins from the Mid-Atlantic Twin Registry and evaluations of their socioeconomic status (SES), social interactions, and use of drugs were obtained. Drug involvement was categorized as never used, tried, or met criteria for abuse or dependence. A co-twin control design was implemented using hierarchical linear modeling to assess whether twins who used drugs experienced lower SES and social support than non-using co-twins. Poorer social functioning in the drug-exposed twin is consistent with a causal relationship, while similar functioning in the drug exposed versus naive twins imply shared genetic or common environmental factors. Use of drugs was not significantly related to any SES measures. However, education and job status appear to share genetic influences with drug abuse/dependence. Lower income was not related to abuse/dependence of drugs. Negative interactions with friends and relatives share genetic factors with use of drugs, but the escalation from trying drugs to abusing them appears to generate discord between the abuser and friends and relatives in a causal fashion. These results indicate that presumptive causal influences of drug abuse/dependence on low SES may actually be mediated by shared genes. Drug use and social discord also appear to have shared genetic factors, but increased levels of drug involvement seem to causally influence social interactions.

Childhood Risk Factors for Heavy Episodic Alcohol Use and Alcohol Problems in Late Adolescence: A Marginal Structural Model Analysis.

OBJECTIVE: This study seeks to clarify the nature of the association between five well-studied late childhood predictors and alcohol-related behaviors in adolescence. METHOD: We examined, in 7,168 subjects from the Avon Longitudinal Study of Parents and Children (ALSPAC), using linear probability and marginal structural models, the association between parental alcohol problems, peer group deviance, antisocial behavior, and low parental monitoring, and sensation seeking assessed at multiple times from ages 12.5 to 18 years and heavy episodic drinking and alcohol problems at ages 16.5, 17.5, and 20 years. RESULTS: Based on the pattern of the attenuation in the association with heavy episodic drinking and alcohol problems from the linear probability to marginal structural models, our five factors were divisible into three groups. For parental alcohol problems, no substantial attenuation was seen. For peer group deviance and antisocial behavior, the associations in the marginal structural models were modestly attenuated (10%-20%). By contrast, for low parental monitoring and sensation seeking, moderate attenuations of 41% and 35%, respectively, were observed. CONCLUSIONS: Our results are consistent with the hypothesis that all or nearly all of the association between parental alcohol problems and heavy episodic drinking and alcohol problems in mid to late adolescence is causal. For peer group deviance and antisocial behavior, the large majority of the associations appear to be causal, but confounding influences are also present. However, for low parental monitoring and sensation seeking, our findings suggest that a substantial proportion of the observed association with alcohol outcomes reflects confounding rather than causal influences.

Personality and major depression: a Swedish longitudinal, population-based twin study.

CONTEXT: Prior studies suggest that the personality traits of neuroticism and extroversion may be related to the liability to major depression (MD). OBJECTIVE: To clarify the magnitude and nature of the association between neuroticism and extroversion and the risk for MD. DESIGN: Longitudinal population-based twin cohort. SETTING: General community. PARTICIPANTS: A total of 20 692 members of same-sex twin pairs from the population-based Swedish Twin Registry who completed a self-report questionnaire assessing neuroticism and extroversion in 1972 and 1973 and were personally interviewed for lifetime history of MD more than 25 years later.Main Outcome Measure Lifetime history of modified DSM-IV MD. RESULTS: Levels of neuroticism strongly predicted the risks for both lifetime and new-onset MD. Twin modeling indicated that the association between neuroticism and MD resulted largely from shared genetic risk factors, with a genetic correlation of +0.46 to +0.47. Levels of extroversion were weakly and inversely related to the risks for lifetime and new-onset MD. This effect disappeared when we controlled for the level of neuroticism. Twin modeling produced similar results. CONCLUSIONS: Results from both longitudinal and genetic analyses support the hypothesis that neuroticism strongly reflects the liability to MD. This association arises largely because neuroticism indexes the genetic risk for depressive illness. However, substantial proportions of the genetic vulnerability to MD are not reflected in neuroticism. By contrast, extroversion is only weakly related to risk for MD.

Age-related changes in heritability of behavioral phenotypes over adolescence and young adulthood: a meta-analysis.

The relative proportions of genetic and environmental variance in behavioral measures have been studied extensively. A growing body of literature has examined changes in heritability measures over time, but we are unaware of any prior efforts to assess developmental heritability changes for multiple behavioral phenotypes using multiple data sources. We have chosen to explore the proportional genetic influences on a variety of behaviors during the genetically and environmentally labile adolescent and young adult years. This meta-analysis examined 8 behavioral domains and incorporated only primary research articles reporting two or more heritability time points in order to minimize the age-to-age error variability. Linear regression analyses revealed significant cross-time heritability increases for externalizing behaviors, anxiety symptoms, depressive symptoms, IQ, and social attitudes and nonsignificant increases for alcohol consumption, and nicotine initiation, but no evidence of heritability changes for attention-deficit/hyperactivity disorder. A variety of mechanisms may underlie these findings including the rising importance of active genotype-environment correlation, an increase in gene expression, or proportional reductions in environmental variance. Additional longitudinal studies and the inclusion of measures of total variance in primary research reports will aid in distinguishing between these possibilities. Further studies exploring heritability changes beyond young adulthood would also benefit our understanding of factors influencing heritability of behavioral traits over the lifespan.

Posttraumatic stress disorder and alcohol dependence: Epidemiology and order of onset.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and alcohol dependence (AD) frequently co-occur; however, epidemiologic studies of temporal associations between PTSD and AD are limited. The aims of this study were (a) to investigate the bidirectional associations between PTSD and AD and (b) to examine demographic and clinical correlates of order-of-onset among individuals with PTSD and AD. METHOD: Participants were 11,103 adults (60.6% women; Mage = 48.7 years, SD = 15.9) from the National Epidemiologic Survey on Alcohol and Related Conditions who endorsed lifetime alcohol consumption and DSM-IV PTSD Criterion A trauma exposure (American Psychiatric Association, 2000). Cox proportional hazards models with time-dependent covariates were used to evaluate bidirectional associations between PTSD and AD. Sex differences were assessed using stratified analyses. RESULTS: After adjusting for demographic, trauma, and alcohol characteristics, PTSD was associated with greater likelihood of subsequent AD (hazard ratio [HR] = 1.359, 95% CI = 1.357-1.362), and AD was associated with greater likelihood of subsequent PTSD (HR = 1.274, 95% CI = 1.271-1.277). Bidirectional associations between PTSD and AD were stronger for women compared with men. Among individuals with PTSD and AD, initial onset of PTSD was associated with younger age of first potentially traumatic event. Initial onset of AD was associated with earlier initiation of alcohol use, earlier onset of heavy alcohol use, family history of alcohol problems, and history of generalized anxiety disorder and social anxiety disorder for women but not men. Initial AD was associated with lifetime panic disorder for men and women. CONCLUSIONS: Etiology of PTSD and AD is heterogeneous, and order of onset may reflect differing risk pathways. (PsycINFO Database Record

Toward a comprehensive developmental model for major depression in men.

OBJECTIVE: The multiple risk factors for major depression are interrelated through poorly understood developmental pathways. In 2002, the authors presented a developmental model for major depression in women. Based on similar methods, they here present an analogous model for men. METHOD: Using data from 2,935 adult male twins, interviewed twice over a 2-4-year period, the authors constructed, by means of structural equation modeling, an integrated etiologic model for major depression that predicts depressive episodes over 1 year from 18 risk factors conceptualized as five developmental "tiers" reflecting childhood, early adolescence, late adolescence, adulthood, and the last year. RESULTS: The best-fitting model, including six correlations and 76 paths, provided a good fit to the data, explaining 49% of the variance in the liability to depressive episodes. The overall results, similar to those seen in women, suggest that the development of major depression results from the action and interaction of three broad pathways of internalizing symptoms, externalizing symptoms, and adversity. Childhood parental loss and low self-esteem were more potent variables in the model in men than in women. Genetic risks for major depression had a broader spectrum of action in men than in women. The pathway to major depression through externalizing symptoms was not more prominent in men than in women. CONCLUSIONS: Major depression in men, as in women, is an etiologically complex disorder influenced by risk factors from multiple domains that act in developmental time. The similarities in etiologic pathways to major depression for men and women outweigh the modest differences.

A Swedish national twin study of lifetime major depression.

OBJECTIVE: Substantial evidence supports the heritability of lifetime major depression. Less clear is whether genetic influences in major depression are more important in women than in men and whether genetic risk factors are the same in the two sexes. It is not known whether genetic effects on major depression are constant across historical cohorts. METHOD: Lifetime major depression was assessed at personal interview by modified DSM-IV criteria in 42,161 twins, including 15,493 complete pairs, from the national Swedish Twin Registry. Twin models were evaluated by using the program Mx. RESULTS: Model fitting indicated that the heritability of liability to major depression was significantly higher in women (42%) than men (29%) and the genetic risk factors for major depression were moderately correlated in men and women. No significant differences were seen in the etiologic roles of genetic and environmental factors in major depression in three cohorts spanning birth years 1900-1958. CONCLUSIONS: In the largest sample to date, lifetime major depression was moderately heritable, with estimates similar to those in prior studies. In accord with some but not other previous investigations, this study suggests both that the heritability of major depression is higher in women than in men and that some genetic risk factors for major depression are sex-specific in their effect. No evidence was found for differences in the roles of genetic and environmental risk factors in major depression in birth cohorts spanning nearly six decades.

Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety.

BACKGROUND: Although substantial evidence suggests that stressful life events predispose to the onset of episodes of depression and anxiety, the essential features of these events that are depressogenic and anxiogenic remain uncertain. METHODS: High contextual threat stressful life events, assessed in 98 592 person-months from 7322 male and female adult twins ascertained from a population-based registry, were blindly rated on the dimensions of humiliation, entrapment, loss, and danger and their categories. Onsets of pure major depression (MD), pure generalized anxiety syndrome (GAS) (defined as generalized anxiety disorder with a 2-week minimum duration), and mixed MD-GAS episodes were examined using logistic regression. RESULTS: Onsets of pure MD and mixed MD-GAS were predicted by higher ratings of loss and humiliation. Onsets of pure GAS were predicted by higher ratings of loss and danger. High ratings of entrapment predicted only onsets of mixed episodes. The loss categories of death and respondent-initiated separation predicted pure MD but not pure GAS episodes. Events with a combination of humiliation (especially other-initiated separation) and loss were more depressogenic than pure loss events, including death. No sex differences were seen in the prediction of episodes of illness by event categories. CONCLUSIONS: In addition to loss, humiliating events that directly devalue an individual in a core role were strongly linked to risk for depressive episodes. Event dimensions and categories that predispose to pure MD vs pure GAS episodes can be distinguished with moderate specificity. The event dimensions that preceded mixed MD-GAS episodes were largely the sum of those that preceded pure MD and pure GAS episodes.