Vivia V. McCutcheon

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.

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.

Three-year follow-up of survivors of a mass shooting episode

This report describes a 3-year follow-up study of survivors of a mass shooting incident. Acute-phase and 1-year follow-up data from this incident have been previously reported. The Diagnostic Interview Schedule/Disaster Supplement was used to assess 116 survivors at 1–2 months and again 1 and 3 years later, with an 85% reinterview rate. Examining the course of postdisaster posttraumatic stress disorder (PTSD) and major depression in individuals allowed detailed consideration of remissions and delayed detection of disorders not possible from data presenting overall rates across different time frames. Only about one half of the PTSD cases identified at any time over 3 years were in remission at the 3-year follow-up. Those who did not recover from PTSD diverged from those who recovered at 3 years by reporting increased numbers of symptoms over time, especially avoidance and numbing symptoms. Although women and people with preexisting disorders were at greater risk for the development of PTSD, these variables did not predict chronicity. Chronicity of PTSD was predicted by functional impairment and seeking mental health treatment at baseline. Chronicity of major depression was predicted by report of family history of depression and treatment for paternal alcohol problems. No delayed cases of PTSD were identified. Studies are needed to compare these characteristics of the course of PTSD with other populations, using consistent methodology to allow valid comparison.

Risk for Suicidal Thoughts and Behavior after Childhood Sexual Abuse in Women and Men

Earlier studies have found an elevated risk for psychopathology and suicidal behavior associated with childhood sexual abuse (CSA); however, the degree to which risk is mediated by depression and posttraumatic stress disorder (PTSD) in women and men remains unclear. We examined these issues in data from a family study of childhood maltreatment (N = 2,559). We found significant CSA-associated risk for depression, PTSD, and suicidal behavior for women and men. In survival analyses controlling for these disorders, we observed persistent but somewhat reduced CSA-associated risk for suicidal ideation and suicide attempt. Our findings suggest that these disorders partially mediate CSA-associated risk.

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.

Alcohol criteria endorsement and psychiatric and drug use disorders among DUI offenders: Greater severity among women and multiple offenders

PURPOSE Data from the Collaborative Study on the Genetics of Alcoholism (COGA), a high-risk family study of alcohol dependence, were used to examine differences in alcohol diagnostic criteria endorsement and psychiatric and drug use disorders by gender and by number of DUI offenses. RESULTS Individuals with two or more DUIs exhibited greater severity of alcohol dependence than those with none or one DUI. This severity was characterized in three ways: (1) higher endorsement of alcohol diagnostic criterion items, with evidence of greater severity among women, (2) higher prevalence of co-occurring lifetime psychiatric disorders, and (3) higher rates of drug use and of dependence on cocaine, stimulants, and, for women only, marijuana and opiates. CONCLUSIONS By examining gradations of disorder within a combination of two high-risk indicators, DUI and family vulnerability, this study provides useful information for clinical research about individuals with chronic and severe alcohol problems. In addition, the observed gender differences in this high-risk sample will contribute to the literature on alcohol dependence among women at the more severe end of the dependence spectrum.

Accumulation of trauma over time and risk for depression in a twin sample

BACKGROUND Few genetically informative studies have examined the effects of different types of trauma on risk for depression over time. The aim of the present study was to examine the relative contributions over time of assaultive trauma, non-assaultive trauma, and familial effects to risk for depression. METHOD Histories of depression and trauma were obtained during structured diagnostic interviews with 5266 (mean age 29.9 years, s.d.=2.4) members of a volunteer Australian twin panel from the general population. Age at first onset of a DSM-IV major depressive episode was the dependent variable. Associations of depression with traumatic events were examined while accounting for the temporal sequence of trauma and depression and familial effects. RESULTS Assaultive traumatic events that occurred during childhood had the strongest association with immediate and long-term risk for depression, and outweighed familial effects on childhood-onset depression for most twins. Although men and women endorsed equal rates of assaultive trauma, women reported a greater accumulation of assaultive events at earlier ages than men, whereas men reported a greater accumulation of non-assaultive events at all ages. CONCLUSIONS Early exposure to assaultive trauma can influence risk for depression into adulthood. Concordance for early trauma is a significant contributor to the familiality of early-onset depression.

Childhood sexual abuse and early substance use in adolescent girls: the role of familial influences

AIM To assess the extent to which the association between childhood sexual abuse (CSA) and early use of alcohol, cigarettes and cannabis in adolescent girls is mediated by risk factors that tend to cluster in families where CSA occurs. DESIGN An abridged version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was administered by telephone. PARTICIPANTS A total of 3761 female twins aged 18-29 (14.6% African American, 85.4% European American). MEASUREMENTS CSA experiences and history of substance use were queried in the SSAGA-based interviews. FINDINGS After controlling for familial influences on early substance use by including co-twin early use status in models, separate Cox proportional hazards regression analyses predicting onset of alcohol, cigarette and cannabis use revealed a significant association with CSA. The effect was observed to age 19 years for cigarettes and to age 21 years for cannabis, but was limited to age 14 years or younger for alcohol, with the most pronounced risk before age 10 [hazard ratio (HR) = 4.59; confidence interval (CI): 1.96-10.74]. CSA-associated risk for initiation of cigarette and cannabis use was also highest in the youngest age range, but the decline with age was much more gradual and the hazard ratios significantly lower (HR: 1.70; CI: 1.13-2.56 for cigarettes and HR: 2.34, CI: 1.57-3.48 for cannabis). CONCLUSIONS Childhood sexual abuse history is a distinct risk factor for use of cigarettes and cannabis, and a very strong predictor of early age at first drink.

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.

The association of specific traumatic experiences with cannabis initiation and transition to problem use: Differences between African-American and European-American women

INTRODUCTION To examine the contribution of trauma exposure to cannabis initiation and transition to first cannabis use disorder (CUD) symptom in African-American (AA) and European-American (EA) emerging adults. METHODS Data are from the Missouri Adolescent Female Twins Study [(N=3787); 14.6% AA; mean age=21.7 (SD 3.8)]. Trauma exposures (e.g. sexual abuse, physical abuse, witnessing another person being killed or injured, experiencing an accident, and experiencing a disaster) were modeled as time-varying predictors of cannabis initiation and transition to CUD symptom using Cox proportional hazards regression. Other substance involvement and psychiatric disorders were considered as time-varying covariates. RESULTS Analyses revealed different trauma-related and psychiatric predictors for cannabis use supporting racially distinct etiologic models of cannabis involvement. For AA women, history of witnessing injury/death or experiencing a life-threatening accident was associated with cannabis initiation across the complete emerging adult risk period while sexual abuse predicted cannabis initiation only before 15 years old. For EA women, history of sexual or physical abuse and major depressive disorder (MDD) predicted cannabis initiation and physical abuse and MDD predicted transition from initiation to first CUD symptom. No association was discovered between trauma exposures and transition to first CUD symptom in AA women. CONCLUSIONS Results reveal trauma exposures as important contributors to cannabis initiation and to a lesser extent transition to CUD symptom, with different trauma types conferring risk for cannabis involvement in AA and EA women. Findings suggest the importance of considering racial/ethnic differences when developing etiologic models of cannabis involvement.