Katherine T. Foster

Genetic and Environmental Influences on the Familial Transmission of Externalizing Disorders in Adoptive and Twin Offspring

IMPORTANCE Twin-family studies have shown that parent-child resemblance on substance use disorders and antisocial behavior can be accounted for by the transmission of a general liability to a spectrum of externalizing disorders. Most studies, however, include only biological parents and offspring, which confound genetic and environmental transmission effects. OBJECTIVE To examine the familial transmission of externalizing disorders among both adoptive (genetically unrelated) and biological relatives to better distinguish genetic and environmental mechanisms of transmission. DESIGN Family study design wherein each family included the mother, father, and 2 offspring, including monozygotic twin, dizygotic twin, nontwin biological, and adoptive offspring. Structural equation modeling was used to estimate familial transmission effects and their genetic and environmental influences. SETTING Participants were recruited from the community and assessed at a university laboratory. PARTICIPANTS A total of 1590 families with biological offspring and 409 families with adoptive offspring. Offspring participants were young adults (mean age, 26.2 years). MAIN OUTCOMES AND MEASURES Symptom counts of conduct disorder, adult antisocial behavior, and alcohol, nicotine, and drug dependence. RESULTS There was a medium effect for the transmission of the general externalizing liability for biological parents (r = 0.27-0.30) but not for adoptive parents (r = 0.03-0.07). In contrast, adoptive siblings exhibited significant similarity on the general externalizing liability (r = 0.21). Biometric analyses revealed that the general externalizing liability was highly heritable (a2 = 0.61) but also exhibited significant shared environmental influences (c2 = 0.20). CONCLUSIONS AND RELEVANCE Parent-child resemblance for substance use disorders and antisocial behavior is primarily due to the genetic transmission of a general liability to a spectrum of externalizing disorders. Including adoptive siblings revealed a greater role of shared environmental influences on the general externalizing liability than previously detected in twin studies and indicates that sibling rather than parent-child similarity indexes important environmental risk factors for externalizing disorders.

Age of Onset and Course of Major Depressive Disorder: Associations With Psychosocial Functioning Outcomes in Adulthood

BACKGROUND Major depressive disorder (MDD) that onsets by adolescence is associated with various deficits in psychosocial functioning. However, adolescent-onset MDD often follows a recurrent course that may drive its associated impairment. METHOD To tease apart these two clinical features, we examined the relative associations of age of onset (adolescent versus adult) and course (recurrent versus single episodes) of MDD with a broad range of psychosocial functioning outcomes assessed in early adulthood. Participants comprised a large, population-based sample of male and female twins from the Minnesota Twin Family Study (MTFS; n = 1252) assessed prospectively from ages 17 to 29 years. RESULTS A recurrent course of MDD predicted impairment in several psychosocial domains in adulthood, regardless of whether the onset was in adolescence or adulthood. By contrast, adolescent-onset MDD showed less evidence of impairment in adulthood after accounting for recurrence. Individuals with both an adolescent onset and recurrent episodes of MDD represented a particularly severe group with pervasive psychosocial impairment in adulthood. CONCLUSIONS The negative implications of adolescent-onset MDD for psychosocial functioning in adulthood seem to be due primarily to its frequently recurrent course, rather than its early onset, per se. The results highlight the importance of considering both age of onset and course for understanding MDD and its implications for functioning, and also in guiding targeted intervention efforts.

Gender differences in the structure of risk for alcohol use disorder in adolescence and young adulthood

BACKGROUND Gender differences in the prevalence of alcohol use disorder (AUD) have motivated the separate study of its risk factors and consequences in men and women. However, leveraging gender as a third variable to help account for the association between risk factors and consequences for AUD could elucidate etiological mechanisms and clinical outcomes. METHOD Using data from a large, community sample followed longitudinally from 17 to 29 years of age, we tested for gender differences in psychosocial risk factors and consequences in adolescence and adulthood after controlling for gender differences in the base rates of AUD and psychosocial factors. Psychosocial factors included alcohol use, other drug use, externalizing and internalizing symptoms, deviant peer affiliation, family adversity, academic problems, attitudes and use of substances by a romantic partner, and adult socio-economic status. RESULTS At both ages of 17 and 29 years, mean levels of psychosocial risks and consequences were higher in men and those with AUD. However, the amount of risk exposure in adolescence was more predictive of AUD in women than men. By adulthood, AUD consequences were larger in women than men and internalizing risk had a stronger relationship with AUD in women at both ages. CONCLUSIONS Despite higher mean levels of risk exposure in men overall, AUD appears to be a more severe disorder in women characterized by higher levels of adolescent risk factors and a greater magnitude of the AUD consequences among women than men. Furthermore, internalizing symptoms appear to be a gender-specific risk factor for AUD in women.

Gender differences in internalizing symptoms and suicide risk among men and women seeking treatment for cannabis use disorder from late adolescence to middle adulthood

Cannabis continues to rise in popularity as the perception of its harmfulness decreases and evidence of its deleterious developmental effect increases. While internalizing distress and suicide risk have been linked with cannabis use problems [DSM-5 cannabis use disorder (CUD); DSM-IV cannabis abuse and dependence] it remains unclear how this association varies over the course of development in treatment-seeking men and women. The current study utilized the National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) to conduct a cross-sectional comparison of internalizing distress and suicide risk among men (n=437) and women (n=163) spanning ages 18-50 who met DSM-5 criteria for CUD. Interactions between gender and developmental stage (i.e., late adolescence, early adulthood, and middle adulthood) were observed for suicide risk and anxiety but not depression problems. Specifically, women seeking CUD treatment in late adolescence and middle adulthood exhibited significantly higher rates of anxiety and suicide risk compared to men seeking treatment during the same developmental stages. Internalizing distress and suicide risk did not differ between treatment-seeking men and women in the early adult stage. Overall, results suggest that the structure of risk for CUD may differ in men and women across the lifespan and that women presenting for CUD treatment during late adolescence and middle adulthood may uniquely benefit from intervention designed to address these elevations in anxiety and suicide risk.

Advancing statistical analysis of ambulatory assessment data in the study of addictive behavior: A primer on three person-oriented techniques

Ambulatory assessment (AA) methodologies have the potential to increase understanding and treatment of addictive behavior in seemingly unprecedented ways, due in part, to their emphasis on intensive repeated assessments of an individuals addictive behavior in context. But, many analytic techniques traditionally applied to AA data - techniques that average across people and time - do not fully leverage this potential. In an effort to take advantage of the individualized, temporal nature of AA data on addictive behavior, the current paper considers three underutilized person-oriented analytic techniques: multilevel modeling, p-technique, and group iterative multiple model estimation. After reviewing prevailing analytic techniques, each person-oriented technique is presented, AA data specifications are mentioned, an example analysis using generated data is provided, and advantages and limitations are discussed; the paper closes with a brief comparison across techniques. Increasing use of person-oriented techniques will substantially enhance inferences that can be drawn from AA data on addictive behavior and has implications for the development of individualized interventions.

Sex Differences in Subjective and Behavioral Responses to Stressful and Smoking Cues Presented in the Natural Environment of Smokers

Introduction Some evidence suggests that female smokers may show more context-dependent smoking and that males may show more stereotyped smoking (regardless of stress or cue exposure). The goal of this study was to characterize sex differences in response to stressful and smoking cues ecologically presented in daily life and variability in day-to-day smoking behavior. Methods Adult smokers (N=177) provided ratings of mood and cigarette craving before and after stress and smoking cues were presented 4 times daily for 14 days via a mobile device. Linear mixed models tested whether: 1) female smokers exhibited greater reactivity to stressful cues than male smokers; 2) pre-cue negative affect increased reactivity to smoking cues more in female smokers than male smokers; 3) across both sexes, greater reactivity to stressful and smoking cues correlated with greater quantity of smoking within a day; and 4) female smokers exhibited greater variability in cigarettes per day [CPD] relative to males. Results Relative to male smokers, female smokers reported greater negative affect, stress, and craving in response to stressful cues, but not smoking cues, after accounting for time since last cigarette and pre-cue responding. No sex differences in CPD or variability in CPD were detected. Days with higher subjective reactivity to cues were not associated with increased smoking, in either males or females. Conclusions Sex differences were observed in response to stress but not smoking cues in the natural environment of regular cigarette smokers. Further research is necessary to evaluate whether stress reactivity in female smokers is associated with reduced latency to smoke following stress exposure in daily life. Implications This study provides naturalistic evidence that female smokers may not be more reactive to smoking cues than males, but experience heightened stress and craving following stress exposure. There was no evidence to support the hypothesis that amount smoked per day varied more for females, relative to males, as a result of more context-driven smoking for females.

Positive and negative effects of internalizing on alcohol use problems from childhood to young adulthood: The mediating and suppressing role of externalizing.

A longstanding hypothesis is that some alcohol use problems (AUP) develop and are maintained through the “self-medication” of internalizing (INT; depression and anxiety) problems. However, their high rate of co-occurrence with one another and with externalizing (EXT; antisocial behavior and impulse control) problems obscures any causal association because EXT may account for the INT-AUP link. Using a large community sample, we estimated prospective effects of INT and EXT on AUP via latent cross-lagged mediation panel spanning 14 years from childhood (ages 9–11) to young adulthood (ages 21–23). After adjusting for the cross-lagged, concurrent, and stability effects across factors, INT decreased AUP risk through its direct and indirect effects and increased AUP risk through shared variance with EXT. Between childhood and young adulthood, unique aspects of INT reduced risk for AUP while aspects of INT shared with EXT increased risk for AUP.

The Gender Risk–Severity Paradox for Alcohol Use Disorder From Adolescence Through Young Adulthood

A large proportion of the public health costs of alcohol use disorder (AUD) can be accounted for by a small percentage of severe cases with a chronic course starting in adolescence and persisting into adulthood. However, chronicity may be a less effective marker of AUD severity in women than men due to a gender risk–severity paradox, wherein comparable levels of risk exposure yield more co-occurring problems for women than men with AUD. To model this paradox, we compared trajectories of alcohol and drug use problems, depression symptoms, and antisocial behavior from ages 17 to 29 in men and women with a persistent, desistent, or no history of AUD. Problems followed a quadratic trajectory (i.e., increases followed by decreases), with gender and AUD chronicity moderating age-related change. Specifically, persistent and desistent courses differentiated the severity of problems more effectively in men while chronicity had less utility for differentiating AUD severity in women.

Pain moderates changes in psychological flexibility but not substance use symptoms during substance use disorder treatment

Pain-related problems frequently complicate substance use disorder (SUD) course and prognosis. However, it is unclear if the negative outcomes associated with co-occurring pain are due to its link with greater SUD severity, disruption of SUD treatment processes, or connection to a third psychological process. The current study modeled the longitudinal effects of pain during a 4-week intensive outpatient treatment (IOP) on SUD symptoms and limited psychological flexibility (PF), a common feature of psychological well being that is commonly restricted in both SUD and pain patients. After controlling for initial severity of SUD symptoms, current pain level at treatment intake moderated change in a sub-component of PF, values commitment, but not SUD symptoms during the IOP. During the treatment, pain level also limited improvement in PF but not self-reported SUD symptoms. Targeting additional increases in psychological flexibility surrounding commitment to values during SUD treatment may help improve outcomes among patients who began treatment with significant pain symptoms.