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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
Several large studies have demonstrated that the liability to smoke cigarettes is strongly genetically influenced. However, the role of genetic and environmental risk factors in the use of other common forms of tobacco use has yet to be studied. Data on the regular use of cigarettes, cigars, pipes, dip (moist snuff), and chewing tobacco from 2634 male twins were analyzed with ACE structural equation models. Twin similarity for regular cigarette and dip use was largely genetic in origin. However, twin resemblance for chewing tobacco was just about equally the result of genes and shared environment, and twin similarity for use of pipes and cigars was entirely the result of shared environmental factors. Thus, the genetic influences on the liability for regular tobacco use appear to vary based on tobacco type. The causes for the use of different forms of tobacco are complex and worthy of further study.
Depressive symptoms reflect depressed mood over a relatively short period of time and are measured using symptom checklists such as the SCL-90. There is some evidence that depressive symptoms are associated with major depression (MD), which is a clinically diagnosed psychiatric illness. Genetic studies of depressive symptomatology suggest a role for genetic factors as well as unique environmental influences. While epidemio-logical research suggests that depressive symptoms may be influenced by sex-specific factors, few genetically informative findings support this result entirely. We used data from male and female same-sex and opposite-sex twin pairs to assess the extent to which genetic, shared and unique environmental factors influence depressive symptoms. Furthermore, we tested for the presence of qualitative and quantitative sex differences in depressive symptoms. Our results suggest that similar to other studies, depressive symptomatology is moderately heritable (31%) with no evidence for shared environmental factors. Our best fitting model suggests that there are no qualitative or quantitative sex differences in depressive symptoms. Our analyses suggest that while there may be mean differences in the levels of depressive symptoms across sexes, the genetic and environmental factors that predispose males and females to depressive symptoms are not different.
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.
Previous analyses in a large population-based sample of female twins indicated that three dimensions of religiosity – personal devotion, personal conservatism and institutional conservatism – were, in different ways, significantly related to current depressive symptoms and substance use and lifetime psychiatric and substance use disorders. Furthermore, personal devotion, but neither personal conservatism nor institutional conservatism, buffered the depressogenic effects of stressful life events (SLEs). We here explore further these results, using linear, logistic and Cox regression models. Eight personality and six demographic variables had distinct patterns of association with the three dimensions. Personal devotion was positively associated with years of education, age, and optimism and negatively correlated with neuroticism. Personal conservatism was negatively associated with education, income, age, mastery and positively correlated with neuroticism. Institutional conservatism was negatively correlated with self-esteem and parental education. Covarying for these 14 variables produced little change in their association with psychiatric and substance use outcomes. The impact of the dimensions of religiosity differed as a function of the SLE category. High levels of both personal devotion and institutional conservatism protected against the depressogenic effects of death and personal illness. High levels of personal conservatism were associated with increased sensitivity to relationship problems. These results suggest that the association between religiosity and low risk for symptoms of depression and substance use may be in part causal. The relationship between dimensions of religiosity and response to SLEs is complex but probably of importance in clarifying the nature of the coping process.
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.
Background. Although an obvious environmental factor influencing drug use, the sources of individual differences in drug availability (DA) are unknown.
Method. This report is based on 1788 adult males from the Mid-Atlantic Twin Registry who participated in a structured telephone interview that included retrospective assessments of DA (cigarette, alcohol, marijuana, cocaine and stimulants) between ages 8 and 25. We fitted a biometric dual change score (DCS) model, adapted for ordinal data, to model latent growth and estimate the genetic and environmental components of variance over time.
Results. DA, despite being considered an environmental risk factor, is under both genetic and environmental control. For cigarette, alcohol, marijuana and cocaine availability, there was an overall increase in additive genetic variance and a decline in shared environmental variance over time. Non-shared environmental variance remained steady. Stimulant availability did not follow this pattern. Instead, there was an upswing in shared environmental effects with increasing age.
Conclusion. We have modeled the genetic and environmental architecture of changes in DA across adolescence. The rise in additive genetic variance over time coincides with acceleration in the expression of individual differences, probably brought on by an increase in personal freedom and a reduction in social constraints. Understanding the etiology of DA is likely to reveal key components, acting directly or indirectly, in the pathway(s) leading to drug initiation, abuse and dependence.
Background. Prior studies report high levels of co-morbidity between major depression (MD) and generalized anxiety disorder (GAD) and suggest that these disorders are closely related genetically. The personality trait of neuroticism (N) is substantially correlated with risk for MD and GAD.
Method. Bivariate twin models were applied to lifetime diagnoses of modified DSM-IV diagnosis of MD and GAD obtained at personal interview in 1998–2003 with 37296 twins from the population-based Swedish Twin Registry. A trivariate Cholesky model with N, MD and GAD was applied to a subset (23280 members of same-sex twin pairs) who completed a self-report questionnaire assessing N in 1972–1973.
Results. In the best-fit bivariate model, the genetic correlation between MD and GAD was estimated at +1·00 in females and +0·74 in males. Individual-specific environmental factors were also shared between the two disorders with an estimated correlation of +0·59 in males and +0·36 in females. In the best-fit trivariate Cholesky model, genetic factors indexed by N impacted equally on risk for MD and GAD in males and females. However, in both sexes, genetic risk factors indexed by N contributed only around 25% to the genetic correlation between MD and GAD.
Conclusion. Genetic risk factors for lifetime MD and GAD are strongly correlated, with higher correlations in women than in men. Although genetic risk factors indexed by the personality trait of N contribute substantially to risk for both MD and GAD, the majority of genetic covariance between the two disorders results from factors not shared with N.
Background. Although caffeine is the most commonly used psychoactive substance and often produces symptoms of toxicity and dependence, little is known, especially in community samples, about the association between caffeine use, toxicity and dependence and risk for common psychiatric and substance use disorders.
Method. Assessments of lifetime maximal caffeine use and symptoms of caffeine toxicity and dependence were available on over 3600 adult twins ascertained from the population-based Virginia Twin Registry. Lifetime histories of major depression (MD), generalized anxiety disorder (GAD) and panic disorder, alcohol dependence, adult antisocial behavior and cannabis and cocaine abuse/dependence were obtained at personal interview. Logistic regression analyses in the entire sample and within monozygotic (MZ) twin pairs were conducted in SAS.
Results. In the entire sample, measures of maximal caffeine use, heavy caffeine use, and caffeine-related toxicity and dependence were significantly and positively associated with all seven psychiatric and substance use disorders. However, within MZ twin pairs, controlling for genetic and family environmental factors, these associations, while positive, were all non-significant. These results were similar when excluding twins who denied regular caffeine use.
Conclusions. Maximal lifetime caffeine intake and caffeine-associated toxicity and dependence are moderately associated with risk for a wide range of psychiatric and substance use disorders. Analyses of these relationships within MZ twin pairs suggest that most of the observed associations are not causal. Rather, familial factors, which are probably in part genetic, predispose to both caffeine intake, toxicity and dependence and the risk for a broad array of internalizing and externalizing disorders.
Background. Although alcohol dependence (AD) and major depression (MD) are highly co-morbid, their causal relationship is unclear. In this longitudinal study, we used a genetically informative population-based twin sample to examine the age-at-onset distributions and the temporal relationship of AD and MD.
Method. Our sample included 7477 twins, whose diagnoses of AD and MD and age-at-onset information were obtained from structured interviews. Individual-level survival analyses were conducted based on 2603 monozygotic (MZ) twins, and co-twin diagnosis was included in models as an index of familiar liability to AD and MD.
Results. The age-at-onset distributions of AD and MD differed substantially. Most onsets of AD were in young adulthood, whereas MD had a flatter distribution across age. Most subjects, especially women, had an onset of MD preceding AD. Prior MD significantly affected risk for developing AD, and this risk decreased over time. By contrast, preceding AD had negligible effects on the risk for future MD. Familial risk was transmitted within disorders but there was little evidence of additional familial liability shared across disorders.
Conclusions. Risk for developing AD was substantially increased by a prior episode of MD. The association was only partially accounted for by familial factors, providing support for a direct causal effect such as self-medication. The etiologic path from AD to MD was insignificant.
Background. In many biomedical disorders, early age at onset (AAO) is an index of high liability to illness which is manifest by an increased risk of illness in relatives. Most but not all prior studies report such a pattern for major depression (MD).
Method. Lifetime MD and AAO were assessed at personal interview using modified DSM-III-R criteria in 13864 twin pairs, including 4229 onsets of MD, from the Swedish National Twin Registry. Analyses were conducted using Cox proportional hazards models.
Results. Controlling for year of birth, gender, zygosity, co-twin history of MD and the interaction of zygosity and co-twin history, the best-fit model showed a significant main effect and a quadratic effect of AAO of MD in the co-twin on the log hazard ratio for MD in the index twin. When examined together, these effects predicted that from the ages of 15 to ~35 years, AAO of MD is moderately negatively related to risk of illness in relatives. However, past age 35, the function flattens out, with little change of risk in relatives with further increases of AAO. Even when the co-twin had a late AAO, the risk in the index twin substantially exceeded that seen when the co-twin had no history of MD.
Conclusion. In this large sample, AAO is a meaningful, albeit modest, index of familial liability to MD. The relationship is nonlinear and results largely from an increased liability in individuals with an early AAO. These results should be interpreted in the context of the limitations of long-term recall.
We know little about the degree to which comorbidity, so commonly seen among psychiatric disorders, arises from variation in normal personality.
To study the degree to which variation in normal personality accounts for the comorbidity of eight common psychiatric and substance use disorders.
Internalising disorders (major depression, generalised anxiety and panic disorders, phobias), externalising disorders (alcohol and drug dependence, anti-social personality and conduct disorders) and personality dimensions of neuroticism, extraversion and novelty seeking were assessed in 7588 participants from a population-based twin registry. The proportion of comorbidity explained by each personality dimension was calculated using structural equation modelling.
Neuroticism accounted for the highest proportion of comorbidity within internalising disorders (20–45%) and between internalising and externalising disorders (19–88%). Variation in neuroticism and novelty seeking each accounted for a modest proportion (10–12% and 7–14%, respectively) of the comorbidity within externalising disorders. Extraversion contributed negligibly
High neuroticism appears to be a broad vulnerability factor for comorbid psychiatric disorders. Novelty seeking is modestly important for comorbid externalising disorders.
Background. Genetic effects upon behaviour are pervasive. To what extent are the many correlates of major depression (MD) due to individual-specific environmental experiences versus genetic factors correlated with risk for MD?
Methods. From a population-based twin registry, we identified 72 female monozygotic pairs discordant for a lifetime history of MD and compared the affected and unaffected members on a wide range of putative correlates of MD.
Results. The affected twin differed from her unaffected co-twin on many variables, eight of which were maximally discriminating: (i) maternal protectiveness; (ii) conflictual parent–child relationship; (iii) low optimism; (iv) current stressful life events; (v) financial difficulties and a history of (vi) phobia, (vii) nicotine dependence; and (viii) divorce. A cluster analysis suggested three ‘environmental pathways' to MD characterized by: (i) childhood vulnerability and anxiety; (ii) acting-out and demoralization; and (iii) interpersonal difficulties.
Conclusion. Important precursors and sequelae of MD originate in environmental experiences unique to the individual and are not mediated through genetic factors or family-of-origin effects. Such environmental factors cause pervasive differences in monozygotic twins discordant for MD, especially in the areas of interpersonal difficulties, psychopathology, social problems and self-concept. These findings should be interpreted in the context of possible retrospective recall bias and the difficulty of distinguishing risk factors from sequelae in co-twin–control studies.
Background. Twin studies have long been used to disentangle
the role of genetic and environmental
factors in the aetiology of psychiatric disorders. However, the validity
of the twin method depends
on the equal environment assumption – that monozygotic (MZ) and dizygotic
(DZ) twins are
equally correlated in their exposure to environmental factors of
aetiological importance for the disorder under study.
Methods. Both members of 822 female–female twin
pairs from a population-based registry
previously assessed for a range of psychiatric and substance use disorders
were asked 12 questions
assessing the similarity of their environmental experiences in childhood
and adolescence. We
examined whether the similarity of environmental experiences
predicted concordance for psychiatric
and substance abuse disorders by both a ‘pair-wise’ and
‘individual’ method utilizing logistic
regression. We also examined smoking initiation, where prior evidence suggested
a role for
adolescent social environment.
Results. Three factors were derived from these items:
‘Childhood treatment’, ‘Co-socialization’
and ‘Similitude’. Members of twin pairs agreed substantially
in their recollections of these
experiences. Compared with DZ twins, MZ twins reported comparable resemblance
childhood treatment, but socialized together more frequently and
reported that parents, teachers
and friends more commonly emphasized their similarities. None of
these three factors significantly
predicted twin resemblance for major depression, generalized anxiety disorder,
phobias, nicotine dependence or alcohol dependence. However, co-socialization
predicted twin resemblance for smoking initiation and perhaps for bulimia.
Conclusion. Differential environmental experiences of MZ and
twins in childhood and
adolescence are unlikely to represent a substantial bias in twin studies
of most major psychiatric and
substance dependence disorders but may influence twin similarity for the
initiation of substance use.
Background. Although replication is the heart of
science, psychiatric geneticists rarely have the opportunity to
replicate findings, especially more than once.
Methods. This article reviews results from three
independent family studies of schizophrenia on which one of us
conducted diagnostic reviews: the Danish Adoption Study (DAS), the
Iowa 500 non-500 family study (IFS), and the Roscommon Family Study
(RFS). We utilized DSM-III or DSM-III-R criteria and meta-analysis
Results. The odds ratios (OR) in personally interviewed,
first degree biological relatives of schizophrenic and matched control
probands for schizophrenia, other non-affective psychoses (ONAP),
schizotypal personality disorder (SPD), unipolar affective illness
(UPAI), bipolar affective illness (BPAI), and anxiety disorders were
homogeneous across studies. For alcoholism, ORs were significantly
heterogeneous. Schizophrenia, SPD and ONAP strongly aggregated in
relatives of schizophrenic probands with decreasing common OR
estimates of 16·2, 5·0 and 4·0, respectively. The
common OR for anxiety disorders was 1·1, indicating no familial
co-aggregation. For UPAI and BPAI, the common ORs exceeded unity
(1·3 and 1·9, respectively), although only the former
was statistically significant.
Conclusions. Schizophrenia strongly aggregates in families
and shares familial factors with SPD and ONAP but not anxiety
disorders. The familial factors of aetiological importance for
schizophrenia and affective illness may be weakly related. With the
exception of alcoholism, the patterns of psychiatric disorders in
relatives of schizophrenic and control probands in these three studies
were sufficiently similar that, despite their methodological
differences, they can probably be viewed as replications of one
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