Results highlight the role of psychiatric and substance use disorders in progression from first drink to AD, underscore the continuity of risk associated with CD and indicate that (with the exception of CD) different factors play a role in transition to AD than in initiation of alcohol use. Distinctions between stages are interpreted in a developmental framework.

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. Method Data 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.

Context Understanding the relative contributions of genetic and environmental factors to trauma exposure, post-traumatic 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.

Objective: To evaluate the possible association between maternal smoking during pregnancy (MSDP) and offspring outcomes of birth weight, pre-term birth, remediation, low scholastic achievement, regular smoking, attention deficit hyperactivity disorder (ADHD) and conduct problems (CD) while controlling for similar behaviors in parents. Methods: Using telephone interviews, data were collected, in 2001 and 2004, as a part of two U.S. 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 1342 unique pregnancies in mothers with a history of regular smoking was utilized for these analyses. The association between MSDP 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: MSDP was associated with decreased birth weight, low scholastic achievement, regular smoking and ADHD. However, the association between MSDP and offspring ADHD was explained by maternal ADHD. MSDP was also associated with earlier age of offspring initiation of smoking and onset of regular smoking. Conclusions: MSDP 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.

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 5,382 twins (2,691 complete pairs), aged 24 to 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.

Aims-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 father's and uncle's substance use dependence (SUD) status reflecting different degrees of genetic and environmental risks to offspring: 1) high genetic, high environmental risk; 2) high genetic, low environmental risk, 3) medium genetic, low environmental risk; and 4) 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 percent of the offspring sample met lifetime criteria for cannabis abuse/ dependence, 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 (HR=2.16; 95% CI=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.

Background We examined timing of substance involvement as a joint function of parental history of alcoholism and parental separation during childhood. Method Data were drawn from a large cohort of female like-sex twins [n = 613 African Ancestry (AA), n = 3550 European or other Ancestry (EA)]. Cox proportional hazards regression was conducted predicting age at first use of alcohol, first alcohol intoxication, first use and regular use of cigarettes, and first use of cannabis and other illicit drugs from dummy variables coding for parental alcoholism and parental separation. Propensity score analysis was also conducted comparing intact and separated families by predicted probability of parental separation. Results In EA families, increased risk of substance involvement was found in both alcoholic and separated families, particularly through ages 10 or 14 years, with risk to offspring from alcoholic separated families further increased. In AA families, associations with parental alcoholism and parental separation were weak and with few exceptions statistically nonsignificant. While propensity score findings confirmed unique risks observed in EA families, intact and separated AA families were poorly matched on risk-factors presumed to predate parental separation, especially parental alcoholism, requiring cautious interpretation of AA survival-analytic findings. Conclusion For offspring of European ancestry, parental separation predicts early substance involvement that is not explained by parental alcoholism nor associated family background characteristics. Additional research is needed to better characterize risks associated with parental separation in African American families.

Background We conducted a genome-wide association study (GWAS) for maximum number of alcoholic drinks consumed in a 24-hour period (“MaxDrinks”), in two independent samples comprised of over 9,500 subjects, following up on our GWAS for alcohol dependence (AD) in European Americans (EAs) and African Americans (AAs). Methods The samples included our GWAS samples (Yale-UPenn) recruited for studies of the genetics of drug or alcohol dependence, and a public available sample: the Study of Addiction: Genetics and Environment (SAGE). Genome-wide association analysis was performed for ∼890,000 single nucleotide polymorphisms (SNPs) using linear association random effects models. European Americans and African Americans were separately analyzed. Results The results confirmed significant associations of the well-known functional loci at ADH1B with MaxDrinks in EAs (rs1229984 Arg48His p= 5.96 x10-15) and AAs (rs2066207 Arg370Cys, p=2.50 x 10-10). The region of significant association on chromosome 4 was extended to LOC100507053 in AAs but not EAs. We also identified potentially novel significant common SNPs for MaxDrinks in EAs in the Yale-UPenn sample: rs1799876 at SERPINC1 on chromosome 1 (4.00 x 10-8) and rs2309169 close to ANKRD36 on chromosome 2 (p=5.58 x 10-9). After adjusting for the peak SNP rs1229984 on ADH1B, rs1799876 was nearly significant (p= 1.99 x 10-7) and rs2309169 remained highly significant (2.12 x 10-9). Conclusions The results provide further support that ADH1B modulates alcohol consumption. Future replications of potential novel loci are warranted. This is the largest MaxDrinks GWAS to date, the first in AAs.