Lifetime drinking trajectories among veterans in treatment for HIV.

BACKGROUND: Previous work on the course of drinking across the life course identified 4 distinct patterns of problem drinking: severe chronic (SC), severe nonchronic (SNC), late onset (LO), and young adult (YA). The purpose of the current study was to determine the generalizability of these findings to a sample of midlife veterans with quite different characteristics from those previously assessed; specifically, veterans in treatment for HIV and veterans in treatment for non-HIV medical issues. METHODS: Participants were drawn from the Veterans Aging Cohort Study that included HIV-positive and matched non-HIV participants. As in our earlier studies, the lifetime drinking history was used to assess drinking phases, and latent growth mixture models were used for analyses. RESULTS: Similar to previous findings, both the HIV+ and non-HIV groups exhibited 4 patterns of drinking (SC, SNC, LO, and YA). SC drinkers had younger ages of onset for drinking and longer duration of smoking. SC drinkers also had the highest rates of cocaine use. Within the HIV+ subsample, SC and LO drinkers increased their drinking after their HIV diagnosis. CONCLUSIONS: This study is the first to examine lifetime drinking patterns among those treated for HIV and provides an excellent starting point for examining finer-grained relationships involving drinking, onset of HIV, and treatment outcomes. Absent from the current study and of particular importance to future work in this area is the need for precise information regarding the temporal relationship between date of HIV diagnosis, onset of treatment, and changes in drinking behavior over the life course.

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.

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.

Suicidal behavior, smoking, and familial vulnerability.

INTRODUCTION: Smoking is a well-established correlate of suicidal behavior. It is not known if familial risk factors contribute to this association. METHODS: Data were obtained via semistructured interviews with 1,107 twin fathers, 1,919 offspring between ages 12-32 years, and 1,023 mothers. Familial vulnerability to nicotine dependence and suicidal behavior was modeled via father and maternal self-report of these behaviors. Multinomial logistic regression models were computed with and without familial risk factors to estimate the association between offspring ever smoking, regular smoking, nicotine dependence, and a 4-level offspring suicide variable: (a) none, (b) ideation, (c) ideation + plan, and (d) ideation + plan + attempt or ideation + attempt. All models were stratified by gender and adjusted for sociodemographics, familial risk factors including parental suicidal behavior, nicotine dependence, and conduct disorder, and offspring conduct disorder, depression, alcohol abuse/dependence, and illicit drug abuse/dependence. RESULTS: After adjusting for covariates and familial risk factors, ever smoking was not significantly associated with suicidal behavior in males and females. In males, regular smoking was associated with ideation + plan (odds ratio [OR] = 5.47; 95% CI: 1.05-28.60), and in females, regular smoking was associated with ideation + plan + attempt or ideation + attempt. In both genders, nicotine-dependent smoking was associated with ideation + plan + attempt or ideation + attempt (males: OR = 6.59; 95% CI: 1.91-22.70, females: OR = 3.37; 95% CI: 1.25-9.04). Comparison of models with and without familial risk factors indicated that there is no mediation of smoking status and suicidal behavior by familial risk. CONCLUSIONS: Smoking and nicotine dependence are correlated with suicidal behaviour. Contributions from familial risk factors did not significantly alter this association.

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.

A latent class analysis of DSM-IV and Fagerström (FTND) criteria for nicotine dependence.

BACKGROUND: Nicotine dependence is associated with considerable morbidity and mortality. Two predominant classification systems, the Diagnostic and Statistical Manual (DSM-IV) and Fagerström Test for Nicotine Dependence (FTND), have been used to measure liability to nicotine dependence, yet few studies have attempted to simultaneously examine both sets of criteria. METHODS: Using a sample of 624 regular smoking individuals who are offspring of Vietnam Era Twin fathers ascertained for an offspring of twin study, we applied latent class analysis to the 7 DSM-IV and the 6 FTND criteria to classify individuals by their nicotine dependence symptom profiles. Post-hoc across-class comparisons were conducted using a variety of smoking-related variables and aspects of psychopathology. Whether a single class identified offspring at high genetic and environmental vulnerability was also investigated. RESULTS: The cross-diagnosis kappa was .30. A 4-class solution fit these data best. The classes included a low DSM-low FTND class and a high DSM-high FTND class; a moderate DSM-moderate FTND class, which was distinguished by moderate levels of smoking and intermediate levels of comorbid psychopathology; and a light smoking-moderate FTND class consisting primarily of lighter smokers with a more recent onset of regular smoking. High genetic and environmental vulnerability to nicotine dependence was noted in all classes with no statistically significant across-class differences. CONCLUSIONS: In general, the DSM-IV and FTND criteria performed similarly to define a continuum of risk for nicotine dependence. The emerging class of light smokers should be further investigated to assess whether they transition to another class or remain as such.

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.

Initial response to cigarettes predicts rate of progression to regular smoking: findings from an offspring-of-twins design.

The aim of this study was to examine the association between initial subjective effects from cigarettes and the rate of progression from first cigarette to regular smoking. Latent class analysis (LCA) was applied to subjective effects data from 573 offspring of twins ranging in age from 14 to 32 years. LCA revealed four classes: 1) High on both pleasurable and physiological responses, 2) Cough only response, 3) High on physiological, low on pleasurable responses, and 4) High on pleasurable, low on physiological responses. Classes of responses were then used to predict time from first cigarette to the onset of regular smoking in a Cox proportional hazards model. Time-varying covariates representing relevant psychiatric and psychosocial factors as well as dummy variables representing the offspring-of-twins design were included in the model. Members of classes 1 and 4 transitioned more rapidly to regular smoking than the classes characterized as low on the pleasurable response dimension. Our findings provide evidence that previously reported associations between pleasurable initial experiences and progression to regular smoking hold true as well for the rate at which that transition occurs. Furthermore, the fact that profiles of responses did not fall into global categories of exclusively pleasurable vs. exclusively negative (physiological) responses suggests the importance of considering both dimensions in combination to characterize risk for smoking-related outcomes.

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.

Subjective effects to cannabis are associated with use, abuse and dependence after adjusting for genetic and environmental influences.

BACKGROUND: Previous reports in adults have suggested that the effects experienced after cannabis use can be described in terms of positive and negative subtypes that are heritable and are associated with abuse and dependence. This study extends existing research by inclusion of adolescents and young adults in an offspring of twins design which makes it possible to take into account genetic and environmental risks for substance use disorder. METHODS: Data were collected from 725 twin members of the Vietnam Era Twin Registry, 839 of their 12-32 year old biological offspring and 427 mothers. Offspring who had ever used cannabis (n=464) were asked the degree to which they typically experienced 13 subjective effects shortly after using cannabis. Latent class analysis (LCA) was used to derive subjective effect classes and logistic regression models were computed to test associations between subjective effect class and heavy cannabis use, abuse and dependence after adjusting for familial risk and psychopathology and sociodemographics. RESULTS: The best fitting LCA model included 4 classes of responders which were characterized as 'high responders' (39%), 'positive responders' (28%), 'mixed/relaxed' (22%), and 'low responders' (11%). Compared to low responders, members of other classes were heavier users (OR range 3.0-11.8). Compared to mixed/relaxed responders and positive responders, high responders were more likely to have cannabis abuse and dependence. CONCLUSIONS: Subjective reactions to cannabis use are associated with use to heavy use, abuse and dependence in adolescents and young adults. This association exists above and beyond the genetic vulnerability for problem cannabis use.

Genetic and environmental contributions to nicotine, alcohol and cannabis dependence in male twins.

AIMS: To compute the common and specific genetic and environmental contributions to nicotine dependence (ND) alcohol dependence (AD) and cannabis dependence (CD). DESIGN: Twin model. PARTICIPANTS: Data from 1874 monozygotic and 1498 dizygotic twin pair members of the Vietnam Era Twin Registry were obtained via telephone administration of a structured psychiatric interview in 1992. MEASUREMENTS: Data to derive life-time diagnoses of DSM-III-R ND, AD and CD were obtained via telephone administration of the Diagnostic Interview Schedule. FINDINGS: The best-fitting model allowed for additive genetic contributions and unique environmental influences that were common to all three phenotypes. Risks for ND and AD were also due to genetic and unique environmental influences specific to each drug. A specific shared environmental factor contributed to CD. CONCLUSIONS: These results suggest that the life-time co-occurrence of ND, AD and CD is due to common and specific genetic factors as well as unique environmental influences, and vulnerability for CD is also due to shared environmental factors that do not contribute to ND and AD. The majority of genetic variance is shared across drugs and the majority of unique environmental influences are drug-specific in these middle-aged men. Because differences between models allowing for specific genetic versus shared environment were small, we are most confident in concluding that there are specific familial contributions-either additive genetic or shared environment-to CD.

Psychiatric and familial predictors of transition times between smoking stages: results from an offspring-of-twins study.

The modifying effects of psychiatric and familial risk factors on age at smoking initiation, rate of progression from first cigarette to regular smoking, and transition time from regular smoking to nicotine dependence (ND) were examined in 1269 offspring of male twins from the Vietnam Era Twin Registry. Mean age of the sample was 20.1 years. Cox proportional hazard regression analyses adjusting for paternal alcohol dependence and ND status and maternal ND were conducted. Both early age at first cigarette and rapid transition from initiation to regular smoking were associated with externalizing disorders, alcohol consumption, and cannabis use. Rapid escalation from regular smoking to ND was also predicted by externalizing disorders, but in contrast to earlier transitions, revealed a strong association with internalizing disorders and no significant relationship with use of other substances. Findings characterize a rarely examined aspect of the course of ND development and highlight critical distinctions in risk profiles across stages of tobacco involvement.

Evidence for specificity of transmission of alcohol and nicotine dependence in an offspring of twins design.

Alcohol dependence (AD) and nicotine dependence (ND) have been shown to co-occur. Results from twin studies implicate the role of genetics in the etiology of both ND and AD with substantial, yet incomplete, overlap. To test for specificity of transmission of AD and ND in an offspring of twins sample we analyzed data from a study of adolescent and adult offspring of twin fathers ascertained from the Vietnam Era Twin Registry. This sample consists of 1213 twin fathers, 862 biologic or rearing mothers, and 1270 offspring. Offspring were allocated to one of four risk groups for AD based on twin fathers' zygosity and father's and cotwins AD history. Offspring DSM-IV AD and ND were measured by structured diagnostic interview. Paternal AD and ND were significantly associated with offspring AD and ND, respectively. Bivariate probit regression results suggest specificity for transmission of AD and ND. This remained constant after controlling for offspring demographics and psychopathology and maternal AD and ND. Despite the substantial genetic overlap between the two disorders, there is evidence for genetic effects specific for AD and ND.

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.

Are substance use, abuse and dependence associated with study participation? Predictors of offspring nonparticipation in a twin-family study.

OBJECTIVE: Although epidemiologic studies have reported that problem drinking is associated with nonresponse to surveys, it is unclear whether parents' alcoholism is associated with nonresponse in their offspring. This question is particularly important to family studies of alcoholism. In the current study we constructed a model of offspring nonparticipation in a twin-family design and computed weights to recapture the distribution of offspring alcohol abuse and dependence. METHOD: In 1999, the first wave of a longitudinal study of offspring of alcoholic twins was conducted via telephone interview with members of the Vietnam Era Twin Registry. The target offspring sample consisted of 2,096 male and female children, of whom 1,270 were successfully interviewed. Offspring response status was classified as participation, refusal or unavailable/no consent. Stepwise logistic regression models were used to identify variables that were significantly associated with one or both types of offspring nonparticipation. A multinomial logit procedure with backward deletion was then used to build a model of the three levels of child response. RESULTS: Paternal alcoholism was not significantly associated with offspring nonresponse, although offspring nonparticipation because of not being located, or being deceased, disabled or unavailable was associated with current paternal smoking, paternal divorce and paternal marital status (after adjustment for other predictor variables). CONCLUSIONS: The most important conclusion to be drawn from current results is that the alcohol abuse and dependence history of fathers should not bias analyses in family studies of alcoholism when data are collected via telephone interview. Study limitations and directions for future research are discussed.

Accuracy of mothers' retrospective reports of smoking during pregnancy: comparison with twin sister informant ratings.

Retrospective assessment of maternal smoking or substance use during pregnancy is sometimes unavoidable. The unusually close relationship of twin sister pairs permits comparison of self-report data versus co-twin informant data on substance use during pregnancy. Information about smoking during pregnancy has been gathered from a series of mothers from an Australian volunteer twin panel (576 women reporting on 995 pregnancies), supplemented in many cases by independent ratings of their smoking by twin sister informants (821 pregnancies). Estimates of the proportion of women who had never smoked regularly (56-58%), who had smoked but did not smoke during a particular pregnancy (16-21%), or who smoked throughout the pregnancy (16-18%), were in good agreement whether based on self-report or twin sister informant data. However, informants underreported cases who smoked during the first trimester but then quit (1-3% versus 7-9% by self-report). Women who smoked throughout pregnancy (by informant report) rarely denied a history of regular smoking (< 1%), although a small proportion of apparent false negative cases were identified where they either denied smoking during a pregnancy (9%) or denied smoking beyond the first trimester (10%). We conclude that retrospective smoking data can safely be used to identify potential associations of later child outcomes with maternal smoking during pregnancy.