Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms.

Data from the Vietnam Era Twin (VET) Registry were analyzed to explore the degree to which the same genetic and environmental factors contribute to childhood conduct disorder symptoms and to alcohol and marijuana dependence symptoms. Data on conduct disorder and alcohol and marijuana dependence were obtained from administration of the Diagnostic Interview Schedule to 1,856 monozygotic and 1,479 dizygotic male-male twin pair members of the VET Registry. Multivariate genetic models were compared to determine the genetic and environmental influences common and or specific to all three phenotypes. A full model that allowed for common genetic and environmental influences to all three phenotypes gave a good fit to the data, but the best fitting reduced model did not allow for a genetic influence on conduct disorder symptoms. Under the best fitting reduced model, genes explained 44.7% of the variance in risk for alcohol dependence symptoms. The genetic liability for symptoms of marijuana dependence was due to a 36.3% specific contribution and a 7.6% contribution from genes common with alcohol dependence symptoms. Family environmental contributions common to all three phenotypes explained 46.7%, 11.9%, and 21.3% of variance in risk for symptoms of conduct disorder, alcohol dependence, and marijuana dependence, respectively. Common family environmental factors contribute to risk of conduct disorder symptoms and alcohol and marijuana dependence symptoms. Common genetic influences contribute to risk of symptoms of alcohol dependence and marijuana dependence. While our findings suggest genes do not contribute to co-morbid conduct disorder symptoms, comparisons with other twin studies suggest that the role of genes in risk for conduct disorder remains uncertain.     

Sex differences in shared genetic and environmental influences between conduct disorder symptoms and marijuana use in adolescents

The association between conduct disorder (CD) symptoms and marijuana use (MU) was assessed in 1,480 adolescent twins participating in the National Longitudinal Study on Adolescent Health. A strong association was found between CD and MU for both males (r=.38, P<.01) and females (r=.31, P<.01). Structural equation modeling on age-corrected rank normalized scores using the program Mx indicated significant gender differences in the genetic and environmental contributions to MU. Additive genetic influences were comparable in size for males (29%) and females (24%). However, for females the influence of common environmental influences was greater (58%) than for males (36%). There was also evidence of greater common environmental influences for females, as well as greater genetic influences for males for CD, but these differences did not reach significance. In addition, for CD common environmental influences did not differ significantly from zero. Additive genetic influences accounted for 61% of the variance in CD, with the remainder being of unique environmental origin. Bivariate genetic analyses suggested a moderate genetic correlation between CD and MU (r(g)=.28) and a low unique environmental correlation (r(e)=.14). These results suggest that CD and MU share genetic influences, while environmental influences tend to be more specific to each behavior. These findings may have implications for the prevention and treatment of CD and substance use among adolescents.     

Cohort differences in genetic and environmental influences on retrospective reports of conduct disorder among adult male twins

BACKGROUND: Rates of child and adolescent conduct disorder (CD) have increased steadily over the past several decades. What is not known is whether the underlying genetic and environmental influences on individual differences in CD have also changed. METHODS: Retrospective reports of antisocial behaviour prior to age 18 were obtained from a population-based sample of 2769 adult males from male-male twin pairs born between 1940 and 1974. Using a summary score of number of CD symptoms, structural equation modelling was used to investigate whether mean level and variation in CD increased with more recent cohorts, and whether any increase in variance could be explained by familial or non-familial factors. RESULTS: Both mean level CD symptoms and variation were increased in more recent cohorts. Model fitting indicated that the primary increase in variance was due to familial factors, most notably, an increase in the shared environmental influences on CD, from 0.01 (95 % CI = 0.00; 0.27) to 0.30 (95 % Cl = 0.01; 0-44). Heritability estimates remained largely unchanged, although an increase in genetic factors could not be ruled out. CONCLUSIONS: Secular changes in sociodemographic factors responsible for increasing rates of CD may also account for the greater magnitude of shared environmental influences on variation in CD found among more recent cohorts.     

Modeling complex genetic and environmental influences on comorbid bipolar disorder with tobacco use disorder

Background  

Comorbidity of psychiatric and substance use disorders represents a significant complication in the clinical course of both disorders. Bipolar Disorder (BD) is a psychiatric disorder characterized by severe mood swings, ranging from mania to depression, and up to a 70% rate of comorbid Tobacco Use Disorder (TUD). We found epidemiological evidence consistent with a common underlying etiology for BD and TUD, as well as evidence of both genetic and environmental influences on BD and TUD. Therefore, we hypothesized a common underlying genetic etiology, interacting with nicotine exposure, influencing susceptibility to both BD and TUD.     

Longitudinal modeling of genetic and environmental influences on self-reported availability of psychoactive substances: alcohol, cigarettes, marijuana, cocaine and stimulants

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.     

Genetic and environmental influences on antisocial behavior and alcohol dependence from adolescence to early adulthood

Genetic and environmental influences on symptoms of adult antisocial behavior (AAB) and alcohol dependence at ages 17, 20, and 24 were examined cross-sectionally and longitudinally in 188 monozygotic and 101 dizygotic male twin pairs. A moderate genetic influence on both AAB and alcohol dependence was found at each age, with a substantial proportion of this influence common to the two disorders, suggesting they share susceptibility genes. Biometrical models showed that continuity effects accounted for most of the stable variance in symptoms of both AAB and alcohol dependence, indicating that genetic and environmental effects associated with each of these disorders were similar at each age. Significant cross-lag effects (effects of alcohol dependence contributing to variance in AAB and vice versa) were observed at ages 20 and 24 for both disorders. The largest and theoretically most interesting of these effects indicated that one sixth of the genetic influence on AAB at age 20 was due to genetic effects associated with alcohol dependence at age 17. Thus, alcohol dependence symptoms at age 17 in particular had an effect on antisocial behavior symptoms at age 20, suggesting that alcohol involvement in adolescence may ensnare otherwise desisting youth in persistent antisocial behavior.     

Changes in genetic and environmental influences on the development of nicotine dependence and major depressive disorder from middle adolescence to early adulthood

This longitudinal study used a representative community sample of same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) to study longitudinal changes in genetic and environmental influences on nicotine dependence (NicD) symptoms and major depressive disorder (MDD) symptoms and the longitudinal relationships between NicD and MDD symptoms at three relatively discrete ages spanning middle adolescence to early adulthood (ages 15, 18, and 21). Clinical interviews were used to assess NicD and MDD symptoms lifetime at age 15 and during the previous 3 years at the two subsequent assessments. Biometric models revealed similar patterns of findings for NicD and MDD. Heritability increased with age, particularly between ages 15 and 18. Shared environmental influences were small, and the proportion of variance attributed to shared environmental influences decreased with age. Nonshared environmental influences were moderate to large in magnitude and were entirely age specific. Both NicD and MDD symptoms showed considerable stability from age 15 to 21, and at each age those with one disorder showed elevated rates of the other. However, a cross-lagged model revealed no longitudinal predictive relationships between MDD symptoms and NicD symptoms after accounting for stability of symptoms within disorders. In summary, the transition between middle and late adolescence is a critical period for developmental shifts in the magnitudes of genetic and environmental influences on both MDD and NicD symptoms. Despite similarities in the development of genetic and environmental influences for the two phenotypes, the association between NicD and MDD reflects concurrent covariation rather than one phenotype being an antecedent influence on the subsequent development of the other.     

Estimating genetic and environmental influences on depressive symptoms in adolescence: differing effects on higher and lower levels of symptoms.

We estimate the relative effect sizes of genetic and environmental influences on both higher and lower levels of depressive symptoms with attention to persistence over a 1-year period in the genetically informative subsample of adolescents participating in the National Longitudinal Study of Adolescent Health (Add Health). Shared environmental effects were significant for persistent higher levels of depressive symptoms but not nonpersistent symptoms. Genetic effects were significant for both persistent and nonpersistent lower levels of depressive symptoms. Nongenetic factors that promote similarity between siblings for high levels of depressive symptoms are important and should be considered in both etiological and applied research. Genetic contributions to lack of susceptibility to depression should be considered in biological models of depression suppression.     

Genetic and environmental influences on obsessional traits and symptoms

A biometrical genetic analysis was carried out on the response of 419 pairs of twins to the 42-item version of Leyton Obsessional Inventory. Just under half the variation in both the Obsessional Trait and Symptom Scales was due to heredity. Multivariate analysis revealed a genetic effect on the development of obsessional personality and also the transmission of a general tendency predisposing to neurotic breakdown. Although the influence of heredity was outweighed by that of the environment, the latter effect showed an absence of general factors and, in particular, of any noticeable effect from the common home environment.     

A twin study of genetic and environmental influences on tobacco initiation, regular tobacco use and nicotine dependence

BACKGROUND: Numerous twin studies have reported significant genetic contributions to the variability of tobacco initiation (TI), while fewer studies have shown similar results for the persistence of smoking behavior, or nicotine dependence (ND). As the development of ND requires regular tobacco use (RTU) which in turn requires TI, a conditional approach is necessary. METHOD: We used structural equation modeling of multi-step conditional processes to examine the relationship between genetic and environmental risk factors for TI, RTU and ND. The tobacco variables were assessed by personal interview in female, male and opposite-sex twin pairs from the population-based Virginia Twin Registry. RESULTS: The results suggested that the liabilities to TI, RTU and ND were correlated. Over 80 % of the variance in liability to TI and RTU were shared, and a smaller proportion was shared between RTU and ND. The heritabilities were estimated at 75 %, 80 % and 60 % respectively for TI, RTU and ND. The variance specific to liability to RTU was entirely accounted for by additive genetic factors. Only a modest part of the heritability in liability of ND was due to genetic factors specific to ND. Shared environmental factors were not significant. No sex differences were found for the sources of variation or causal paths, but prevalences were significantly greater in males versus females. CONCLUSIONS: This study showed significant overlap in the contribution of genetic factors to individual differences in TI, RTU and ND. Furthermore, there was evidence for significant additional genetic factors specific to RTU and ND.     

Schema therapy for patients with borderline personality disorder and comorbid alcohol dependence: A multiple-baseline case series design study

This study tested the effectiveness of schema therapy (ST) for borderline personality disorder (BPD) and comorbid alcohol dependence (AD). Twenty patients participated in a case series study with multiple baselines. The baseline phase consisted of treatment as usual. It was followed by a case conceptualization phase, an experiential techniques phase and a behavioural change phase. Patients showed a significant decrease in BPD and AD symptoms; change was mainly accomplished in the experiential techniques phase, with medium to large effect sizes. Three months after termination of therapy, 68% of the patients had remitted from BPD, and the number of drinking days decreased clearly. This study shows that, although treatment is challenging in this group of patients, meaningful change can be obtained in patients with BPD and AD using ST.     

Beyond prevalence and pattern: problematic extent of alcohol and substance use among adolescents in Ibadan South-west Nigeria

Background

Previous research on adolescent alcohol/substance use in Nigeria had focused on the pattern of use without consideration for the extent of use. Socio-demographic correlates have also not been well explored. Information about socio-demographic correlates can also inform target-points in preventive strategies. Knowledge of the prevalence of problematic pattern of alcohol/substance use can inform the inclusion of rehabilitation strategies in intervention policies.

Objectives

To determine the prevalence, pattern and extent-as well as socio-demographic correlates-of alcohol/substance use among a cohort of adolescents in Nigeria.

Methods

Pattern and extent of alcohol/substance use was examined using the CRAFFT instrument.

Results

A total of 538 adolescents with a mean age of 15.1 ± 1.4years returned completed questionnaires. 12-month prevalence of alcohol and other substance use was 21.4%. About 46% of those who reported use of alcohol or any other substance had a CRAFFT score of >2 which suggests problematic pattern of use. Older age, male gender, parental alcohol and substance and lower than average school performance were independently associated with 12-momth use of alcohol or any other substance.

Conclusions

Adolescent alcohol and substance use is common in Nigeria and a large proportion of users show a problematic pattern of use that warrants rehabilitative intervention.     

Genetic influences on DSM-III-R drug abuse and dependence: A study of 3,372 twin pairs

Research and clinical experience indicate that drug use disorders tend to run in families. The objective of this study was to distinguish between the family environment and genetic factors as the source of this observed family resemblance. Data were collected by telephone interview from members of the Vietnam Era Twin Registry, comprising male twin pairs who served in the U.S. military between 1965 and 1975. There were 3,372 pairs in which both twins participated. Drug use disorder was defined as receiving a diagnosis of drug abuse or dependence according to DSM-III-R; 10.1% of the sample had abused or been dependent on at least one illicit drug. A significant difference between concordance rates for monozygotic (26.2%) vs. dizygotic (16.5%) twins indicated a genetic influence on drug use disorder. Biometrical modeling indicated that genetic factors (34% of the variance), the environment shared by twins (28% of the variance), and the nonshared environment (38% of the variance) had significant influences of similar magnitudes on the individual's risk of developing a drug use disorder. These results support the application of molecular genetic approaches to elucidate the genetic influence on drug use disorder, as well as the potential efficacy of environmental intervention to reduce risk. © 1996 Wiley-Liss, Inc.     

Overlap and specificity of genetic and environmental influences on excessive acquisition and difficulties discarding possessions: Implications for hoarding disorder

A reluctance to discard items, leading to severely cluttered living spaces, is the landmark feature of hoarding disorder (HD). Many, but not all, individuals with HD also excessively acquire, buy or even steal items that they do not need and for which no space is available. In DSM‐5, “excessive acquisition” can be coded as a specifier of HD. Despite their consistent co‐occurrence, the question of whether excessive acquisition and difficulties discarding possessions share a common etiology remains unanswered. The current study sought to flesh out this relationship by examining the extent of shared genetic and environmental influences on the association between excessive acquisition and difficulties discarding in a community sample of adult, female twins. A total of 5,022 female twins (2,529 pairs; mean age = 55.5 years) completed a self‐report measure of hoarding symptoms, including items assessing excessive acquisition and difficulties discarding. The data were analyzed using bivariate twin modeling methods in the statistical program Mx. As expected, we found a strong phenotypic correlation (0.63) between excessive acquisition and difficulty discarding items. Both traits were moderately heritable. The genetic correlation between the traits was estimated to be 0.77 (95% CI: 0.69–0.85), indicating a substantial but imperfect genetic overlap. The non‐shared environmental correlation (0.50 [95% CI: 0.42–0.57]), though lower, was also significant. The findings demonstrate a substantial genetic, and more modest environmental, etiological overlap between the excessive acquisition of possessions and difficulties discarding them, providing a possible explanation for their frequent co‐occurrence in HD. However, given that the etiological overlap is not perfect, unique etiological influences, particularly environmental, on each phenotype seem plausible. © 2013 Wiley Periodicals, Inc.     

Genetic and environmental influences on premenstrual symptoms in an Australian twin sample

BACKGROUND: We aimed to explore the prevalence and factor structure of premenstrual symptoms in a sample of Australian twins; to investigate phenotypic associations between reported premenstrual symptoms, personality and reproductive dimensions; and to identify the relative contributions of genes and environment to premenstrual symptoms and the extent of genetic and environmental covariation with the personality trait Neuroticism and lifetime major depression. METHOD: Seven hundred and twenty female twin pairs (454 monozygotic and 266 dizygotic) from the Australian National Health and Medical Research Council Twin Register reported on experience of 17 premenstrual symptoms during the previous 12 months. In the same questionnaire twins also responded to questions on symptom states, and personality dimensions including neuroticism. Interview data enabling diagnosis of lifetime history of DSM-IV major depression were also available. We fitted univariate and multivariate genetic models to the data. RESULTS: Most frequently reported symptoms were breast tenderness/pain and bloating/weight gain, followed by affective symptoms. Twelve-month prevalence was 24% for the combination of symptoms and functional interference meeting a very rough approximation of DSM-III-R criteria for late luteal dysphoric disorder. Principal factor analysis identified a single premenstrual (PMS) factor. Additive genetic influences (44% of total variance) were identified for PMS. Although we found genetic correlations of 0.62 between reported PMS and neuroticism, and 0 70 with lifetime major depression, 39 % of the genetic variance of PMS was not explained by these factors. CONCLUSIONS: Our findings support the existence of genetic influences on premenstrual symptoms, but we were unable to distinguish between liability to symptom experience and symptom reporting. Retrospective reporting may have contributed to our finding that PMS genes were shared in part with neuroticism and liability to lifetime major depression.     

Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design

BACKGROUND: Children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems [e.g. attention deficit hyperactivity disorder (ADHD)]. While there is evidence that genetic influences and prenatal nicotine and/or alcohol exposure play separate roles in determining risk of ADHD, little has been done on determining the joint roles that genetic risk associated with maternal alcohol use disorder (AUD) and prenatal risk factors play in determining risk of ADHD. METHOD: Using a children-of-twins design, diagnostic telephone interview data from high-risk families (female monozygotic and dizygotic twins concordant or discordant for AUD as parents) and control families targeted from a large Australian twin cohort were analyzed using logistic regression models. RESULTS: Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD. Adjustment for prenatal smoking, which remained significantly predictive, did not remove the significant genetic association between maternal AUD and offspring ADHD. CONCLUSIONS: While maternal smoking during pregnancy probably contributes to the association between maternal AUD and offspring ADHD risk, the evidence for a significant genetic correlation suggests: (i) pleiotropic genetic effects, with some genes that influence risk of AUD also influencing vulnerability to ADHD; or (ii) ADHD is a direct risk-factor for AUD.