Carolyn E. Sartor

Common genetic and environmental contributions to post-traumatic stress disorder and alcohol dependence in young women.

BACKGROUND The few genetically informative studies to examine post-traumatic stress disorder (PTSD) and alcohol dependence (AD), all of which are based on a male veteran sample, suggest that the co-morbidity between PTSD and AD may be attributable in part to overlapping genetic influences, but this issue has yet to be addressed in females.MethodData were derived from an all-female twin sample (n=3768) ranging in age from 18 to 29 years. A trivariate genetic model that included trauma exposure as a separate phenotype was fitted to estimate genetic and environmental contributions to PTSD and the degree to which they overlap with those that contribute to AD, after accounting for potential confounding effects of heritable influences on trauma exposure. RESULTS Additive genetic influences (A) accounted for 72% of the variance in PTSD; individual-specific environmental (E) factors accounted for the remainder. An AE model also provided the best fit for AD, for which heritability was estimated to be 71%. The genetic correlation between PTSD and AD was 0.54. CONCLUSIONS The heritability estimate for PTSD in our sample is higher than estimates reported in earlier studies based almost exclusively on an all-male sample in which combat exposure was the precipitating traumatic event. However, our findings are consistent with the absence of evidence for shared environmental influences on PTSD and, most importantly, the substantial overlap in genetic influences on PTSD and AD reported in these investigations. Additional research addressing potential distinctions by gender in the relative contributions of genetic and environmental influences on PTSD is merited.

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.

Common Heritable Contributions to Low-Risk Trauma, High-Risk Trauma, Posttraumatic Stress Disorder, and Major Depression

CONTEXT Understanding the relative contributions of genetic and environmental factors to trauma exposure, posttraumatic stress disorder (PTSD), and major depressive disorder (MDD) is critical to developing etiologic models of these conditions and their co-occurrence. OBJECTIVES To quantify heritable influences on low-risk trauma, high-risk trauma, PTSD, and MDD and to estimate the degree of overlap between genetic and environmental sources of variance in these 4 phenotypes. DESIGN Adult twins and their siblings were ascertained from a large population-based sample of female and male twin pairs on the basis of screening items for childhood sexual abuse and physical abuse obtained in a previous assessment of this cohort. SETTING Structured psychiatric telephone interviews. PARTICIPANTS Total sample size of 2591: 996 female and 536 male twins; 625 female and 434 male nontwin siblings. MAIN OUTCOME MEASURE Lifetime low- and high-risk trauma exposure, PTSD, and MDD. RESULTS In the best-fitting genetic model, 47% of the variance in low-risk trauma exposure and 60% of the variance in high-risk trauma exposure was attributable to additive genetic factors. Heritable influences accounted for 46% of the variance in PTSD and 27% of the variance in MDD. An extremely high degree of genetic overlap was observed between high-risk trauma exposure and both PTSD (r = 0.89; 95% CI, 0.78-0.99) and MDD (r = 0.89; 95% CI, 0.77-0.98). Complete correlation of genetic factors contributing to PTSD and to MDD (r = 1.00) was observed. CONCLUSIONS The evidence suggests that almost all the heritable influences on high-risk trauma exposure, PTSD, and MDD, can be traced to the same sources; that is, genetic risk is not disorder specific. Individuals with a positive family history of either PTSD or MDD are at elevated risk for both disorders and should be closely monitored after a traumatic experience for symptoms of PTSD and MDD.

Evidence for an interaction between age at first drink and genetic influences on DSM-IV alcohol dependence symptoms.

BACKGROUND Research suggests that individuals who start drinking at an early age are more likely to subsequently develop alcohol dependence. Twin studies have demonstrated that the liability to age at first drink and to alcohol dependence are influenced by common genetic and environmental factors, however, age at first drink may also environmentally mediate increased risk for alcohol dependence. In this study, we examine whether age at first drink moderates genetic and environmental influences, via gene x environment interactions, on DSM-IV alcohol dependence symptoms. METHODS Using data on 6,257 adult monozygotic and dizygotic male and female twins from Australia, we examined the extent to which age at first drink (i) increased mean alcohol dependence symptoms and (ii) whether the magnitude of additive genetic, shared, and nonshared environmental influences on alcohol dependence symptoms varied as a function of decreasing age. Twin models were fitted in Mx. RESULTS Risk for alcohol dependence symptoms increased with decreasing age at first drink. Heritable influences on alcohol dependence symptoms were considerably larger in those who reported an age at first drink prior to 13 years of age. In those with later onset of alcohol use, variance in alcohol dependence was largely attributable to nonshared environmental variance (and measurement error). This evidence for unmeasured gene x measured environment interaction persisted even when controlling for the genetic influences that overlapped between age at first drink and alcohol dependence symptoms. CONCLUSIONS Early age at first drink may facilitate the expression of genes associated with vulnerability to alcohol dependence symptoms. This is important to consider, not only from a public health standpoint, but also in future genomic studies of alcohol dependence.

The association between cannabis abuse and dependence and childhood physical and sexual abuse: evidence from an offspring of twins design

AIM This study examines the association between childhood physical abuse (CPA) and sexual abuse (CSA) and the development of cannabis abuse and dependence among adolescents and young adults while controlling for genetic and environmental risk factors. DESIGN To control for familial risk differences related to paternal drug dependence that might confound the relationship between CSA and CPA and cannabis abuse/dependence, we created four groups based on fathers and uncles substance use dependence (SUD) status reflecting different degrees of genetic and environmental risks to offspring: (i) high genetic, high environmental risk; (ii) high genetic, low environmental risk; (iii) medium genetic, low environmental risk; and (iv) low genetic, low environmental risk. PARTICIPANTS Adolescent and young adult offspring of monozygotic and dizygotic US military veteran twin fathers (n = 819). MEASUREMENTS Data on CPA and CSA, DSM-IV offspring cannabis abuse/dependence, other SUD and psychopathology and maternal and paternal SUD and psychopathology were collected via semi-structured telephone interview. FINDINGS Twenty-three per cent of the offspring sample met life-time criteria for cannabis abuse/dependence and 8.55% and 12.82% reported CSA and CPA, respectively. Offspring exposed to CSA, but not CPA, were at significantly greater risk of developing cannabis abuse/dependence compared to those who had not experienced CSA (hazard ratio = 2.16; 95% confidence interval = 1.48-3.16) after controlling for genetic and familial environmental risk and offspring gender, alcohol abuse and dependence and conduct disorder. CONCLUSIONS These results indicate that there are effects of CSA on development of cannabis abuse/dependence in addition to the genetic and familial environmental risk imparted by having a drug-dependent father.

Correlates of smoking cessation in a nationally representative sample of U.S. adults

Persistent cigarette smoking is associated with significant morbidity and mortality. Correlates of difficulty quitting smoking include psychopathology, such as major depressive disorder, and problems with other substances, such as alcoholism. In addition, socio-demographic risk (e.g. poverty) and protective (e.g. living in a region with stringent tobacco laws) influences can modify risk for persistent cigarette smoking. Using data on 17,919 individuals with a lifetime history of smoking 100 or more cigarettes, from a nationally representative U.S. sample, we examine the constellation of risk and protective factors that correlate with smoking cessation (defined as remaining smoke-free in the past 12 months) across four cohorts: young (18-31 years), intermediate-aged (32-43 years), middle-aged (44-60 years) and older (61-99 years) adults. Using survival analyses, we demonstrate that in addition to a history of DSM-IV nicotine dependence, which is negatively associated with smoking cessation, living below the poverty line is also associated with persistent smoking across all age cohorts. Residents over the age of 31 years living on the U.S. West Coast are less likely to be persistent smokers as well. Major depressive disorder is associated with persistent smoking, but interestingly, only in middle-aged and older adults. Alcoholism and a family history of substance use problems are both correlated with persistent smoking but only in older adults. Here, we find evidence for psychopathology that may hinder successful quit attempts during the developmental period when a majority of quit attempts are made (early to mid-40s). However, our analyses also highlight the important benefits of effective tobacco legislation on the U.S. West Coast and urge policy makers to actively consider addressing issues surrounding tobacco taxation and the impact of poverty on tobacco use, in addition to the risks posed by co-occurring psychiatric problems and other substance use disorders.

Timing of first alcohol use and alcohol dependence: evidence of common genetic influences

AIMS To estimate the magnitude of genetic and environmental influences on timing of first alcohol use and alcohol dependence (AD) and to quantify the overlap in these influences across the two alcohol-related outcomes. PARTICIPANTS The sample consisted of 5382 twins (2691 complete pairs), aged 24-36 years, from the Australian Twin Registry. MEASUREMENTS History of alcohol use and DSM-IV alcohol dependence were assessed by structured telephone interview. FINDINGS In both sexes, the relationship between age at first alcohol use and risk for AD followed a linear trend, such that the highest rates of AD were observed in individuals who began drinking at an earlier than average age (14 years or younger). Heritability estimates for timing of first alcohol use and AD were 36% and 53%, respectively. Shared environmental factors accounted for 15% of variance in initiation. There was no evidence of shared environmental influences on AD. The genetic correlation between timing of first alcohol use and AD was 0.59. CONCLUSIONS Findings highlight the substantial role of genetics in the development of AD and the early manifestation of that genetic risk in the timing of alcohol use initiation which, unlike AD, is also influenced to a modest degree by shared environmental factors. The considerable overlap in heritable influences-and the virtual absence of overlap in individual-specific environmental influences-on initiation of alcohol use and AD indicates that the association between age at first drink and AD is attributable in large part to common genetic sources of variance.

Age at trauma exposure and PTSD risk in young adult women

The aim of the current study was to test the independent and joint contributions of 8 different types of trauma to posttraumatic stress disorder (PTSD) risk using data from a young adult female cohort. Associations of traumatic events with PTSD onset were examined using Cox proportional hazards models. Differences in risk as a function of age at trauma were tested. Childhood sexual assault, physical abuse, and neglect were stronger predictors of PTSD onset than adolescent and early adult occurrence of these events in individual models. In a model including all traumatic events, differential risk by age remained for sexual assault and physical abuse. Early sexual assault was the strongest predictor of risk, but additional traumatic events increased risk even in its presence.

Common genetic influences on the timing of first use for alcohol, cigarettes, and cannabis in young African-American women.

The risks associated with early age at initiation for alcohol, cigarette, and cannabis use are well documented, yet the timing of first use has rarely been studied in genetically informative frameworks, leaving the relative contributions of genetic and environmental factors to age at initiation largely unknown. The current study assessed overlap in heritable and environmental influences on the timing of initiation across these three substances in African-American women, using a sample of 462 female twins (100 monozygotic and 131 dizygotic pairs) from the Missouri Adolescent Female Twin Study. Mean age at the time of interview was 25.1 years. Ages at first use of alcohol, cigarettes, and cannabis were gathered in diagnostic interviews administered over the telephone. Standard genetic analyses were conducted with substance use initiation variables categorized as never, late, and early onset. Variance in the timing of first use was attributable in large part to genetic sources: 44% for alcohol, 62% for cigarettes, and 77% for cannabis. Genetic correlations across substances ranged from 0.25 to 0.70. Shared environmental influences were modest for alcohol (10%) and absent for cigarettes and cannabis. Findings contrast with reports from earlier studies based on primarily Caucasian samples, which have suggested a substantial role for shared environment on substance use initiation when measured as lifetime use. By characterizing onset as timing of first use, we may be tapping a separate construct. Differences in findings may also reflect a distinct etiological pathway for substance use initiation in African-American women that could not be detected in previous studies.

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.