Genetic architecture of reciprocal social behavior in toddlers: Implications for heterogeneity in the early origins of autism spectrum disorder.

Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.

Differences between White and Black young women in the relationship between religious service attendance and alcohol involvement.

BACKGROUND AND OBJECTIVES: We examined the associations of religious attendance during childhood (C-RA) and adulthood (A-RA) with alcohol involvement (ever drinking, timing of first alcohol use, and alcohol use disorder [AUD]) in White and Black female twins. As genetic and environmental factors influence religious attendance and alcohol involvement, we examined the extent to which they contribute to their association. METHODS: Data on 3,234 White and 553 Black female twins (18-29 years) from the Missouri Adolescent Female twin Study. Significant correlations between C-RA or A-RA and alcohol involvement were parsed into their additive genetic, shared environmental, and individual-specific environmental sources. RESULTS: C-RA was associated with ever drinking and timing of first alcohol use in Whites. A-RA was associated with ever drinking and AUD in both Whites and Blacks. Shared environmental influences did not contribute to alcohol or religiosity phenotypes in Blacks. In Whites, the association between C-RA and alcohol was due to shared environmental influences, whereas the association between A-RA and alcohol was attributable to additive genetic, shared environmental, and individual-specific environmental sources. Individual-specific environment and genetics contributed to associations between A-RA and ever drinking and AUD, respectively, in Blacks. CONCLUSIONS: Factors other than C-RA contribute to lower rates of alcohol involvement in Blacks. Shared environment does not contribute to links between A-RA and alcohol involvement in Blacks. SCIENTIFIC SIGNIFICANCE: The protective impact of childhood religiosity on alcohol use and misuse is important in Whites and is due to familial factors shared by religiosity and alcohol involvement. (Am J Addict 2017;26:437-445).

Parental Separation and Offspring Alcohol Involvement: Findings from Offspring of Alcoholic and Drug Dependent Twin Fathers.

BACKGROUND: We examined associations between parental separation during childhood and offspring alcohol involvement, adjusting for genetic and environmental risks specific to parental alcohol (AD) and cannabis/other illicit drug dependence (DD). METHODS: The sample consisted of 1,828 offspring of male twins from the Vietnam Era Twin (VET) Registry, who completed a telephone diagnostic interview. Cox proportional hazards regression analyses were conducted predicting onset of first use, transition from first use to first AD symptom, and transition from first use to AD diagnosis from paternal and avuncular AD and DD history, parental separation, and offspring and family background characteristics. Paternal/avuncular DD/AD was based on the DSM-III-R; offspring and maternal AD were based on DSM-IV criteria. RESULTS: Paternal DD/AD predicted increased offspring risk for all transitions, with genetic effects suggested on rate of transitioning to AD diagnosis. Parental separation was predictive of increased risk for early alcohol use, but a reduced rate of transition to both AD symptom onset and onset of AD. No interactions between separation and familial risk (indexed by paternal or avuncular DD/AD) were found. CONCLUSIONS: Findings highlight the contribution of both parental separation and paternal substance dependence in predicting timing of offspring alcohol initiation and problems across adolescence into early adulthood.

Associations of alcohol, nicotine, cannabis, and drug use/dependence with educational attainment: evidence from cotwin-control analyses.

BACKGROUND: Although substance use is associated with reduced educational attainment, this association may be owing to common risk factors such as socioeconomic disadvantage. We tested whether alcohol, nicotine, and illicit drug use and dependence were associated with lifetime educational attainment after controlling for familial background characteristics. METHODS: Data were from a 1987 questionnaire and a 1992 telephone diagnostic interview of 6,242 male twins (n = 3,121 pairs; mean age = 41.9 years in 1992) who served in the U.S. military during the Vietnam era and therefore, were eligible for educational benefits after military service. Reduced educational attainment (<16 years) was examined in twin pairs discordant for substance use history. Substance use and dependence risk factors assessed were early alcohol and cannabis use, daily nicotine use, lifetime cannabis use, and alcohol, nicotine, cannabis, and any illicit drug dependence. RESULTS: Three significant differences were observed between at-risk twins and their cotwins: Compared to their low-risk cotwins, likelihood of completing <16 years of education was significantly increased for the following: (i) twins who used alcohol before age 18 (adjusted OR = 1.44; 95% CI: 1.02 to 2.05), (ii) twins with a lifetime alcohol dependence diagnosis (adjusted OR = 1.76; 95% CI: 1.27 to 2.44), and (iii) twins who had used nicotine daily for 30 or more days (adjusted OR = 2.54, 95% CI: 1.55 to 4.17). However, no differences in education were observed among twin pairs discordant for cannabis initiation, early cannabis use, or cannabis, nicotine, or any illicit drug dependence. CONCLUSIONS: Even in a veteran population with access to military educational benefits, early alcohol use, alcohol dependence, and daily nicotine use remained significantly associated with years of education after controlling for shared familial contributions to educational attainment. The association between other substances and educational attainment was explained by familial factors common to these substance use phenotypes and adult educational attainment.

Testing the equal environments assumption in the Children of Twins design.

In a Children of Twins (COT) design, the environmental and genetic risk of a child is, in part, dependent upon the status of the father and the father's cotwin. The logic of the COT method breaks down if the zygosity of the twin pair is confounded with the environment provided to the child (a version of the Equal Environment Assumption, EEA). If MZ twin fathers see each other more often than DZ twin fathers, and a child's uncle is the affected twin in discordant pairs, this could increase the environmental risk of children of MZ over that of DZ discordant twins. The current study was designed to test the EEA in the COT design, specifically in children of alcohol and drug dependent fathers. Results indicated that MZ twins did have more contact than DZ twins. Regression analyses were conducted to predict child externalizing symptom counts from father's zygosity group status, level of contact with father's cotwin, and their interaction. Results found no significant interaction between father's zygosity and the higher level of cotwin contact (seen in MZ twins) in predicting several measures of offspring externalizing risk. The results of this study suggested that the COT design does not confound zygosity with differences in environmental risk exposure, findings that support the validity of the EEA within this research context.

The effects of maternal smoking during pregnancy on offspring outcomes.

OBJECTIVE: To evaluate the possible association between maternal smoking during pregnancy and offspring outcomes of birth weight, pre-term birth, remediation, low scholastic achievement, regular smoking, attention deficit hyperactivity disorder and conduct problems while controlling for similar behaviors in parents. METHODS: Using telephone interviews, data were collected, in 2001 and 2004, as a part of two United States offspring-of-twins projects. Fathers, who were twins participating in the Vietnam Era Twin Registry, their female spouse and their offspring were interviewed - information on 1,342 unique pregnancies in mothers with a history of regular smoking was utilized for these analyses. The association between maternal smoking during pregnancy and birth weight, pre-term birth, remediation, low scholastic achievement, regular smoking, attention deficit hyperactivity disorder and conduct disorder while controlling for similar behaviors in parents, was examined using regression. RESULTS: Maternal smoking during pregnancy was associated with decreased birth weight, low scholastic achievement, regular smoking and attention deficit hyperactivity disorder. However, the association between maternal smoking during pregnancy and offspring attention deficit hyperactivity disorder was explained by maternal attention deficit hyperactivity disorder. Maternal smoking during pregnancy was also associated with earlier age of offspring initiation of smoking and onset of regular smoking. CONCLUSIONS: Maternal smoking during pregnancy may influence certain offspring outcomes via mechanisms that are independent from genetic risk attributable to comorbid conditions. Assisting expecting mothers with their smoking cessation efforts will likely provide widespread health benefits to both mother and offspring.

Transitions in alcohol use over time: a survival analysis.

BACKGROUND: The current study examined the predictors of the onset of alcohol use as well as predictors of remission and relapse, both from heavy drinking and from alcohol dependence. Similarities and differences in both clinical and psychosocial predictors across the transitions were examined. METHODS: A sample of men from the Vietnam Era Twin Registry (N = 1769) completed an assessment of lifetime drinking history, which allowed age markers for starting and stopping different drinking patterns. The men also completed various assessments regarding personality, alcohol motives, and psychiatric diagnoses. Survival analyses were used to examine the predictors of the three transitions of onset, remission, and relapse for the phenotypes of heavy drinking and of alcohol dependence, censoring the individuals who had not yet experienced an event. RESULTS: As expected, predictors of onset for drinking, heavy drinking, and alcohol dependence were largely consistent and included externalizing symptomology, nicotine dependence, and cotwin history of drinking as risk factors. Predictors of remission from heavy drinking, somewhat similarly to remission from alcohol dependence, included the risk factor of externalizing disorders but also, as predicted, included more risk and protective factors in the psychosocial realm that were not predictors of onset. Contrary to our prediction, relapse to heavy drinking and alcohol dependence were predicted largely by unique psychosocial risk and protective factors including social and coping motives. CONCLUSION: Current findings extend the findings of past research to remission and relapse in the later decades of life and have implications for treatment of alcohol use problems.

Paternal alcoholism and offspring ADHD problems: a children of twins design.

OBJECTIVE: A recent Children-of-Female-Twin design suggests that the association between maternal alcohol use disorder and offspring ADHD is due to a combination of genetic and environmental factors, such as prenatal nicotine exposure. We present here a complementary analysis using a Children-of-Male-Twin design examining the association between paternal alcoholism and offspring attention deficit hyperactivity problems (ADHP). METHODS: Children-of-twins design: offspring were classified into 4 groups of varying genetic and environmental risk based on father and co-twin's alcohol dependence status. RESULTS: Univariate results are suggestive of a genetic association between paternal alcohol dependence and broadly defined offspring ADHP. Specifically, offspring of male twins with a history of DSM-III-R alcohol dependence, as well as offspring of non-alcohol dependent monozygotic twins whose co-twin was alcohol dependent, were significantly more likely to exhibit ADHP than control offspring. However, multivariate models show maternal variables independently predicting increased risk for offspring ADHP and significantly decreased support for a genetic mechanism of parent-to-child transmission. CONCLUSIONS: In support of earlier work, maternal variables (i.e., maternal ADHD and prenatal exposure) were strongly associated with child ADHP; however, the role of paternal alcohol dependence influences was not definitive. While genetic transmission may be important, the association between paternal alcohol dependence and child ADHP is more likely to be indirect and a result of several pathways.

Customizing a clinical app to reduce hazardous drinking among veterans in primary care.

Within the Veterans Health Administration (VHA), 15-30% of patients seen in primary care are identified as hazardous drinkers, yet the vast majority of these patients receive no intervention. Time constraints on providers and patient-level barriers to in-person treatment contribute to this problem. The scientific literature provides a compelling case that mobile-based interventions can reduce hazardous drinking and underscores the role of peer support in behavioral change. Here, we describe the benefits of using a clinical app-Step Away-to treat hazardous drinking among VHA primary care patients as well as an approach to customizing the app to maximize its engagement and effectiveness with this population. We highlight the value of integrating use of Step Away with telephone support from a trained VHA peer support specialist. This type of integrated approach may provide the key therapeutic components necessary to generate an effective and easily implemented alcohol use intervention that can be made available to VHA primary care patients who screen positive for hazardous drinking but are unwilling or unable to attend in-person treatment. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Residual Effects: Young Adult Diagnostic Drinking Predicts Late-Life Health Outcomes.

OBJECTIVE: This study examined the residual effects of young adult diagnostic drinking on health outcomes four decades later in late life. Results were differentiated by drinking status during midlife. METHOD: A subsample of Vietnam Era Twin Registry members, all of whom had a lifetime diagnosis of alcohol dependence, was grouped according to life span drinking patterns as assessed by the Lifetime Drinking History interview in 2001. Those drinking at diagnostic levels (endorsing three or more alcohol dependence symptoms) before age 30 were then grouped based on their midlife drinking status (i.e., drinking at diagnostic levels vs. at minimal [nonsymptomatic] levels throughout midlife). Linear (or logistic) regression models were used to examine the association between life span drinking patterns and health outcomes in late life (about age 64). RESULTS: Those who drank at diagnostic levels in young adulthood and in midlife exhibited significant health liabilities on every late-life health measure; those who drank at diagnostic levels for 5 or more years in young adulthood but drank only at minimal levels or not at all in midlife still exhibited similar liabilities on most late-life health measures. Only those individuals who drank diagnostically for less than 5 years in young adulthood displayed normal levels of late-life health. CONCLUSIONS: This study identified residual effects resulting from persistent young adult diagnostic drinking (5 or more years) that resulted in negative health outcomes in late life even after decades of remission. There is a distal but surprisingly strong association between persistent early life diagnostic drinking and late-life morbidity.

Psychiatric morbidity is linked to problem drinking in midlife among alcohol-dependent men: a co-twin control study.

OBJECTIVE: Prior research on predictors of problem drinking has been limited because of an inability to attribute an unambiguous environmental explanation to observed findings. Using a prospective co-twin control design, we examined the extent to which a history of psychiatric symptoms exerts an environmental influence on problem drinking in midlife that is unconfounded by genetic underpinnings. METHOD: Participants were 367 complete male twin pairs (208 monozygotic, 159 dizygotic) from the Vietnam Era Twin Registry who were assessed in midlife as part of the Family Twin Study (Mage = 51.4 years, SD = 2.8). Twin pairs who were concordant for a lifetime diagnosis of an alcohol use disorder (AUD) in 1992 were selected for participation and were reinterviewed in 2001 to measure symptoms of AUD (i.e., problem drinking) since the prior assessment (past 10 years). RESULTS: Within-pair differences in lifetime symptom counts of several psychiatric disorders measured in 1992 (i.e., major depression, dysthymia, generalized anxiety disorder, panic disorder, antisocial personality, mania, and posttraumatic stress disorder) were significantly associated with within-pair differences in AUD symptoms in the subsequent 10 years. CONCLUSIONS: A history of psychiatric problems, particularly one marked by internalizing symptoms, appears to be linked to problem drinking in midlife above and beyond the confounding influence of genetic effects and underscores the potential value of integrated interventions for comorbidity to address problem drinking among individuals during this period of the life course.

Religion/spirituality, risk, and the development of alcohol dependence in female twins.

The contention that Religion/Spirituality (R/S) influences the development of alcohol dependence (AD) is increasingly supported, but risk factors have not been adequately examined together with protective R/S factors so as to determine the nature and relative strength of these domains at different stages in the development of alcoholism. Secondary data analysis of a sample of 4,002 young adult female twins used conditional Cox proportional hazards survival models to examine three distinct stages in the development of alcoholism: years to initiation of drinking, years from first drink to at-risk drinking, and years from at-risk drinking to AD. Risk and protective factors from models of alcoholism etiology and studies of R/S dimensionality were modeled simultaneously as predictors of each discrete stage and compared. Findings demonstrated that both risk factors and R/S variables influenced initiation of alcohol use; only R/S variables influenced subsequent progression to at-risk drinking; and risk factors primarily influenced further progression to AD. Protective factors (R/S variables being an exemplar) appeared to be critical determinants of intermediate-stage progression, thus suggesting that R/S factors and other psychosocial interventions might be particularly effective in delaying progression toward AD at this stage. In contrast, after the onset of at-risk drinking, the influence of (genetically based) risk factors appeared to accelerate AD regardless of most other influences. Thus, the timing of psychosocial interventions appears critical to their potency and impact.

Parent, sibling and peer associations with subtypes of psychiatric and substance use disorder comorbidity in offspring.

BACKGROUND: Parental substance use disorder (SUD) is associated with a range of negative offspring outcomes and psychopathology, but the clustering of these outcomes into subtypes has seldom been examined, nor have the familial and environmental contexts of these subtypes been reported. The present study examines the clustering of offspring lifetime substance use and psychiatric disorders into subtypes and characterizes them in terms of familial and non-familial influences using an offspring-of-twins design. METHOD: Telephone-administered diagnostic interviews were used to collect data on psychiatric disorders and SUD from 488 twin fathers, 420 biological mothers and 831 offspring. Latent class analysis (LCA) was used to derive subtypes of lifetime comorbidity in offspring. Familial risk and environmental variables associated with each subtype (i.e., parenting, childhood physical or sexual abuse, perceived sibling and peer substance use) were identified using multinomial logistic regression. RESULTS: Four classes identified by LCA were characterized as (1) unaffected, (2) alcohol abuse/dependence, (3) alcohol abuse/dependence comorbid with anxiety and depression, and (4) alcohol, cannabis abuse/dependence and nicotine dependence comorbid with conduct disorder. Inconsistent parenting, childhood physical/sexual abuse, and perceived sibling and peer substance use were significantly associated with profiles of offspring comorbidity after adjusting for familial vulnerability. Some associations were specific (i.e., perceived peer alcohol use to the AUD class), while others were general (peer smoking to all 3 comorbidity classes). CONCLUSIONS: We observed distinct subtypes of psychiatric and SUD comorbidity in adolescents and young adults. Subtypes of offspring psychopathology have varied associations with parental psychopathology, family environment, and sibling and peer behaviors.

Alcohol milestones, risk factors, and religion/spirituality in young adult women.

OBJECTIVE: The alcoholism research literature has long reported a significant, reliable, and inverse association between alcohol use disorders and religion/spirituality (R/S), and this is also evident in the period of highest risk--adolescence and young adulthood. In the treatment area, both clinical and mutual-help programs for alcohol use disorders often include a spiritual component, and outcome studies validate the efficacy of such programs. Even so, the alcoholism-R/S relationship is little understood. METHOD: The current study examined data from an existing sample of 4,002 female adolescents/young adults and their families. Data analyses examined five demographic, nine R/S, and eight risk-factor variables as predictors of five alcohol milestones: initial drink, first intoxication, regular use, heavy consumption, and alcohol dependence. RESULTS: Results affirmed the known association between alcoholism risk factors and alcohol use milestones and also found moderate to strong associations between most R/S variables and these risk factors and milestones. A multivariate model simultaneously examining both sets of variables found that specific risk factors and specific R/S variables remained significant predictors of alcohol use milestones after accounting for all other variables. Mediation and moderation tests did not find evidence that R/S accounted for or qualified the relationship between alcohol risk factors and alcohol milestones. CONCLUSIONS: This study confirmed the multidimensional role of R/S influences within the etiological network of alcoholism risk and protective factors in adolescents/young adults and found R/S dimensions to be independent and substantial influences on alcohol use disorders rather than mediators or moderators of other risks.

Parent, sibling and peer influences on smoking initiation, regular smoking and nicotine dependence. Results from a genetically informative design.

We sought to determine whether parenting, sibling and peer influences are associated with offspring ever smoking, regular smoking and nicotine dependence (ND) after controlling for familial factors. We used a twin-family design and data from structured diagnostic surveys of 1919 biological offspring (ages 12-32 years), 1107 twin fathers, and 1023 mothers. Offspring were classified into one of four familial risk groups based on twin fathers' and their co-twins' history of DSM-III-R nicotine dependence. Multivariate multinomial logistic regression was used to model familial risk, paternal and maternal parenting behavior and substance use, sibling substance use, and friend and school peer smoking, alcohol and drug use. Ever smoking was associated with increasing offspring age, white race, high maternal pressure to succeed in school, sibling drug use, and friend smoking, alcohol and drug use. Offspring regular smoking was associated with these same factors with additional contribution from maternal ND. Offspring ND was associated with increasing offspring age, male gender, biological parents divorce, high genetic risk from father and mother ND, maternal problem drinking, maternal rule inconsistency and sibling drug use, and friend smoking, alcohol and drug use. Friend smoking had the largest magnitude of association with offspring smoking. This effect remains after accounting for familial liability and numerous parent and sibling level effects. Smoking interventions may have greatest impact by targeting smoking prevention among peer groups in adolescent and young adult populations.

Childhood religious affiliation and alcohol use and abuse across the lifespan in alcohol-dependent men.

The current study examined the relationship between childhood religious affiliation and alcohol use across the life span. A sample of 931 men (average age of 51) from the Vietnam Era Twin Registry, which includes an overrepresentation of alcohol-dependent men, completed the Lifetime Drinking History interview, which assessed drinking across the life span. Childhood religious affiliation was obtained from the men's spouse/partner. Affiliations were subdivided into four categories: nonreligious, accommodating (religions that are relatively more accepting of the larger culture), differentiating (religions that set themselves apart from the larger culture), and Catholic. Differences in a variety of alcohol use variables by religious affiliation were examined, as well as the protective effect of childhood religious affiliation on three alcohol use variables at 5-year intervals from age 20 to age 50. Significant differences were found for abstinence, regular drinking, and current quantity-frequency (QFI) scores, with individuals in differentiating religions having the highest rates of abstinence/nonregular drinking and the lowest consumption levels. When examining QFI and alcohol dependence symptoms and diagnoses over time, the nonreligious group had more alcohol use than the religious groups, with the differentiating affiliations showing the least alcohol use. The differences between affiliations were not always significant, but the consistent pattern suggests that childhood religious affiliation may continue to affect alcohol use even into adulthood.

Alcoholism, personality, and religion/spirituality: an integrative review.

A review of the literature on the relationships between alcoholism, personality, and religion identified patterns that may help explain the inverse association between alcoholism and religion/spirituality (R/S). Personality plays a central role in two etiological models of alcoholism. The personality traits of high behavioral undercontrol (low Agreeableness and low Conscientiousness) and high negative affect (high Neuroticism) are both significantly related to higher alcohol use. Religiosity is also correlated with these traits, but in the opposite direction (e.g., with low behavioral undercontrol and low negative affect). Thus, the personality profiles associated with alcoholism and religion are the inverse of one another. In addition, evidence suggests that R/S moderates genetic variation on both Neuroticism and Disinhibition (part of behavioral undercontrol). Implications are discussed in terms of competing explanatory models: a basic research model which argues for genetically-determined stability in personality and alcoholism risk, and a clinical treatment model which argues for the primacy of environmental interventions in treatment and the possibility of personality change as a pathway to recovery.

Patterns of use, sequence of onsets and correlates of tobacco and cannabis.

BACKGROUND: While most individuals initiate their use of tobacco prior to onset of cannabis use, recent reports have identified a smaller subset of youth who report onset of cannabis use prior to tobacco use. In this study, we characterize patterns of cannabis and tobacco use (tobacco but not cannabis, cannabis but not tobacco or both) and compare the factors associated with onset of tobacco before cannabis and cannabis before tobacco. METHODS: Data on 1812 offspring aged 12-32 years, drawn from two related offspring of Vietnam Era twin studies, were used. Individuals were divided into tobacco but not cannabis (T), cannabis but not tobacco (C) and users of both substances (CT). Those who used both could be further classified by the timing of onset of tobacco and cannabis use. Multinomial logistic regression was used to characterize the groups using socio-demographic and psychiatric covariates. Furthermore, data on parental smoking and drug use was used to identify whether certain groups represented greater genetic or environmental vulnerability. RESULTS: 22% (N=398) reported T, 3% (N=55) reported C and 44% reported CT (N=801). Of the 801 CT individuals, 72.8% (N=583), 9.9% (N=77) and 17.3% (N=139) reported onset of tobacco before cannabis, cannabis before tobacco and onsets at the same age. C users were as likely as CT users to report peer drug use and psychopathology, such as conduct problems while CT was associated with increased tobacco use relative to T. Onset of tobacco prior to cannabis, when compared onset of cannabis before tobacco or reporting initiation at the same age was associated with greater cigarettes smoked per day, however no distinct factors distinguished the group with onset of cannabis before tobacco from those with initiation at the same age. CONCLUSION: A small subset of individuals report cannabis without tobacco use. Of those who use both cannabis and tobacco, a small group report cannabis use prior to tobacco use. Follow-up analyses that chart the trajectories of these individuals will be required to delineate their course of substance involvement.

Effect of paternal alcohol and drug dependence on offspring conduct disorder: gene-environment interplay.

OBJECTIVE: Not only are substance-use disorders and externalizing disorders frequently comorbid, they often co-occur in families across generations. The current study examined the role of genetic and environmental influences in the relationship between paternal histories of drug dependence or alcohol dependence and offspring conduct disorder using an offspring-of-twins design. METHOD: Participants were male twins (n = 1,774) from the Vietnam Era Twin Registry, their offspring (n = 1,917), and mothers of the offspring (n = 1,202). Twins had a history of drug dependence, alcohol dependence, or neither. Based on the father's and his co-twin's drug-dependence or alcohol-dependence history and zygosity, risk groups were constructed to reflect different levels of genetic and environmental risk that were then used to predict offspring conduct disorder. RESULTS: After controlling for potentially confounding variables, the offspring of men with a history of drug dependence or alcohol dependence had significantly higher rates of conduct disorder, compared with offspring of men without this history. Offspring at higher genetic risk had higher rates of conduct disorder. High-risk offspring at lower environmental risk had lower rates of conduct disorder but only in the case of paternal drug-dependence risk. Lower environmental risk did not influence rates of offspring conduct disorder when the father had an alcohol-dependence history. CONCLUSIONS: Genetic risk associated with both paternal drug-dependence and paternal alcohol-dependence histories predicted offspring conduct-disorder risk, but only risk associated with paternal drug-dependence history was mitigated by having a low-risk environment. These results demonstrated a significant gene-environment interaction effect.

Contribution of parental psychopathology to offspring smoking and nicotine dependence in a genetically informative design.

OBJECTIVE: It is not known if parental psychiatric disorders have an independent effect on offspring smoking after controlling for genetic and environmental vulnerability to nicotine dependence. We tested if parental alcohol, drug, or conduct disorders; antisocial personality disorder; depression; and anxiety disorders remained significant predictors of offspring smoking initiation, regular smoking, and nicotine dependence before and after adjusting for genetic and environmental risk for nicotine dependence. METHOD: Data were obtained via semi-structured interviews with 1,107 twin fathers, 1,919 offspring between the ages of 12 and 32, and 1,023 mothers. Genetic and environmental liability for smoking outcomes was defined by paternal and maternal nicotine dependence. Multinomial logistic regression models were computed to estimate the risk for offspring trying cigarettes, regular smoking, and the Fagerström Test for Nicotine Dependence (FTND) as a function of parental psychopathology and sociodemographics before and after adjusting for genetic and environmental vulnerability to nicotine dependence. RESULTS: Before adjusting for genetic and environmental risk for nicotine dependence, ever trying cigarettes was associated with maternal depression, regular smoking was associated with maternal alcohol dependence and maternal conduct disorder, and FTND was associated with paternal and maternal conduct disorder and antisocial personality disorder. No parental psychopathology remained significantly associated with regular smoking and FTND after adjusting for genetic and environmental vulnerability to nicotine dependence in a multivariate model. CONCLUSIONS: The association between parental psychopathology and offspring smoking outcomes is partly explained by genetic and environmental risk for nicotine dependence. Point estimates suggest a trend for an association between parental antisocial personality disorder and offspring regular smoking and nicotine dependence after adjusting for genetic and environmental vulnerability. Studies in larger samples are warranted.