Leah S. Richmond-Rakerd

A closer look at the evidence for sex differences in the genetic and environmental influences on gambling in the National Longitudinal Study of Adolescent health: from disordered to ordered gambling

BACKGROUND AND AIMS To reconcile an inconsistency in the disordered gambling literature by revisiting a previous study that claimed to find evidence for large gender differences in the magnitude of genetic and environmental influences. DESIGN Univariate structural equation twin models were fitted to decompose the variation in gambling behavior into additive genetic, shared environmental and unique environmental influences. SETTING United States. PARTICIPANTS Participants were 1196 same-sex and unlike-sex twins (18-28 years of age, 49% male, 51% female) from the National Longitudinal Study of Adolescent Health (Add Health). MEASUREMENTS Eight questions about normative and problematic gambling involvement were assessed by in-person interview. Although disordered gambling symptoms were assessed, the number of individuals who were administered these questions precluded twin analysis, including analysis of potential gender differences. Of the eight questions, only three were deemed usable for twin analysis-these were all questions about normative gambling involvement. FINDINGS Individual differences in (non-disordered) gambling involvement were explained completely by family [C = 38% (30-46%)] and unique environmental factors [E = 62% (54-70%)]. There was no evidence for genetic factors (A = 0), nor was there evidence for sex differences (Δχ(2) = 1.23, d.f. = 2, P = 0.54). CONCLUSIONS There appears to be no evidence for gender differences in the genetic contributions to disordered gambling. Family environment appears to play a significant role in explaining individual differences in (non-disordered) gambling involvement among emerging adults.

Genetic and environmental influences on the ages of drinking and gambling initiation: evidence for distinct aetiologies and sex differences.

AIMS To investigate the genetic and environmental contributions to age at first drink (AFD) and age first gambled (AFG), assess their overlap and examine sex differences. DESIGN Univariate twin models were fitted to decompose the variation in AFD and AFG into additive genetic, shared environmental and unique environmental factors. Bivariate genetic models were fitted to assess the genetic and environmental contributions to the sources of covariation in AFD and AFG. SETTING National Australian Twin Registry. PARTICIPANTS A total of 4542 same-sex and opposite-sex twins aged 32-43 years, 42% male and 58% female. MEASUREMENTS AFD and AFG were assessed via structured psychiatric telephone interviews. Age of onset was treated as both continuous and categorical (early/late onset). FINDINGS AFD and AFG were modestly correlated (r = 0.18). Unique environmental influences explained a substantial proportion of the variation in both AFD (0.55, 95% confidence interval [CI] = 0.50-0.61) and AFG (0.66, 95% CI = 0.59-0.72), but these influences were uncorrelated (rE  = 0.01). Additive genetic factors explained a notable proportion of variation in AFG (0.21, 95% CI = 0.003-0.39), while shared environmental factors were important for AFD (0.31, 95% CI = 0.15-0.46). Among men, genetic factors influenced variation in AFG but not in AFD and shared environmental factors influenced variation in AFD but not in AFG. Among women, shared environmental factors influenced variation in both AFD and AFG, but these environmental factors were not significantly correlated (rC  = 0.09). CONCLUSIONS Among Australian twins, age at first drink and age first gambled are influenced by distinct unique environmental factors, and the genetic and environmental underpinnings of both phenotypes differ in men and women.

Investigating the influence of prenatal androgen exposure and sibling effects on alcohol use and alcohol use disorder in females from opposite-sex twin pairs.

BACKGROUND There are robust sex differences for alcohol phenotypes, with men reporting more drinking and alcohol use disorder (AUD) symptoms than women. However, the sources of these effects are not completely understood. Sex hormones, a substantial biological sex difference, exert neurobehavioral influences and are candidates for influencing sex differences in alcohol phenotypes. This study investigated the effects of prenatal androgens based on the hypothesis of prenatal hormone transfer, which posits that hormones from one twin influence the development of a cotwin. METHODS This study compared female twins from opposite-sex (OSF) and same-sex (SSF) pairs to investigate associations between prenatal androgens and alcohol phenotypes. Additional analyses distinguished prenatal and postnatal effects by comparing OSFs and SSFs with a close-in-age older (CAO) brother. RESULTS OSFs endorsed more lifetime AUD symptoms than SSFs (d = 0.14). Females with a CAO brother reported greater intoxication frequency (d = 0.35), hangover frequency (d = 0.24), typical drinking quantity (d = 0.33), and max drinks (i.e., the most drinks ever consumed in a 24-hour period; d = 0.29). Controlling for postnatal effects, OSFs still endorsed more lifetime AUD symptoms than SSFs with a CAO brother (d = 0.16). CONCLUSIONS Prenatal exposure to a male cotwin was associated with increases in AUD symptoms, above the effect of postnatal exposure to a male sibling. Prenatal exposure to a male cotwin was not associated with increases in other alcohol-related phenotypes, but postnatal exposure to older male siblings produced medium effect sizes for indicators of alcohol consumption. Sex differences in AUDs, but not alcohol use, may be partially due to the neurodevelopmental effects of prenatal androgens. However, sibling effects may be larger than any effect of prenatal androgen exposure.

Test of a Potential Causal Influence of Earlier Age of Gambling Initiation on Gambling Involvement and Disorder: A Multilevel Discordant Twin Design

The premise that an association between an earlier age of gambling initiation and the later development of disordered gambling is causal has not yet been empirically examined. The current study used a multilevel discordant twin design to examine the nature of this association. Participants were 3,546 same-sex twins (mean age = 37.7 years) from the Australian Twin Registry who completed a telephone interview that included an extensive assessment of gambling and related behaviors. Multilevel models were employed to estimate individual (within-twin-pair comparison) and family level (between-twin-pair comparison) effects, as well as the cross-level interaction between these effects. Family-level effects (genetic or environmental factors shared by family members) of age of gambling initiation robustly predicted later adult gambling frequency and disorder; the evidence for individual-level effects (unique factors not shared by family members, including a potentially causal effect of earlier age of gambling onset) was less robust. The results of this study suggest that the relation between earlier age of gambling initiation and later gambling involvement and disorder is primarily noncausal; efforts to delay the onset of gambling among young people may not necessarily reduce the number who later go on to develop gambling-related problems.

Birth cohort and sex differences in the age of gambling initiation in the United States: evidence from the National Comorbidity Survey Replication

Youth gambling has become a significant public health concern, and it appears that individuals are gambling at younger ages than they did in earlier generations. We tested this question by examining birth cohort differences in the age of onset of gambling in a national epidemiologic survey. Data were drawn from the United States National Comorbidity Survey Replication, a nationally representative general population survey of adults born 1904–84. Individuals were divided into four birth cohorts. The cohorts were compared on their lifetime gambling involvement and age of onset of gambling. Significant birth cohort and sex differences were found in the age of gambling initiation, with more recently born cohorts starting to gamble at progressively earlier ages, and men starting to gamble at younger ages than women. The mean age of onset of gambling for individuals born before 1942 was 32.9 years, and for those born between 1973 and 1984 it was 16.9 years. The overall mean ages of onset of gambling were 20.8 for men and 26.4 for women, but more recently born women appear to be ‘catching up’ with their male counterparts. This decreasing age of gambling initiation may help explain the increasing prevalence of disordered gambling in the United States.

A Novel Tobacco Use Phenotype Suggests the 15q25 and 19q13 Loci May Be Differentially Associated with Cigarettes per Day and Tobacco-Related Problems

Introduction Tobacco use is associated with variation at the 15q25 gene cluster and the cytochrome P450 (CYP) genes CYP2A6 and CYP2B6. Despite the variety of outcomes associated with these genes, few studies have adopted a data-driven approach to defining tobacco use phenotypes for genetic association analyses. We used factor analysis to generate a tobacco use measure, explored its incremental validity over a simple indicator of tobacco involvement: cigarettes per day (CPD), and tested both phenotypes in a genetic association study. Methods Data were from the University of California, San Francisco Family Alcoholism Study (n = 1942) and a Native American sample (n = 255). Factor analyses employed a broad array of tobacco use variables to establish the candidate phenotype. Subsequently, we conducted tests for association with variants in the nicotinic acetylcholine receptor and CYP genes. We explored associations with CPD and our measure. We then examined whether the variants most strongly associated with our measure remained associated after controlling for CPD. Results Analyses identified one factor that captured tobacco-related problems. Variants at 15q25 were significantly associated with CPD after multiple testing correction (rs938682: p = .00002, rs1051730: p = .0003, rs16969968: p = .0003). No significant associations were obtained with the tobacco use phenotype; however, suggestive associations were observed for variants in CYP2B6 near CYP2A6 (rs45482602: ps = .0082, .0075) and CYP4Z2P (rs10749865: ps = .0098, .0079). Conclusions CPD captures variation at 15q25. Although strong conclusions cannot be drawn, these finding suggest measuring additional dimensions of problems may detect genetic variation not accounted for by smoking quantity. Replication in independent samples will help further refine phenotype definition efforts. Implications Different facets of tobacco-related problems may index unique genetic risk. CPD, a simple measure of tobacco consumption, is associated with variants at the 15q25 gene cluster. Additional dimensions of tobacco problems may help to capture variation at 19q13. Results demonstrate the utility of adopting a data-driven approach to defining phenotypes for genetic association studies of tobacco involvement and provide results that can inform replication efforts.

Most of the genetic covariation between major depressive and alcohol use disorders is explained by trait measures of negative emotionality and behavioral control

BACKGROUND Mental health disorders commonly co-occur, even between conceptually distinct syndromes, such as internalizing and externalizing disorders. The current study investigated whether phenotypic, genetic, and environmental variance in negative emotionality and behavioral control account for the covariation between major depressive disorder (MDD) and alcohol use disorder (AUD). METHOD A total of 3623 members of a national twin registry were administered structured diagnostic telephone interviews that included assessments of lifetime histories of MDD and AUD, and were mailed self-report personality questionnaires that assessed stress reactivity (SR) and behavioral control (CON). A series of biometric models were fitted to partition the proportion of covariance between MDD and AUD into SR and CON. RESULTS A statistically significant proportion of the correlation between MDD and AUD was due to variance specific to SR (men = 0.31, women = 0.27) and CON (men = 0.20, women = 0.19). Further, genetic factors explained a large proportion of this correlation (0.63), with unique environmental factors explaining the rest. SR explained a significant proportion of the genetic (0.33) and environmental (0.23) overlap between MDD and AUD. In contrast, variance specific to CON accounted for genetic overlap (0.32), but not environmental overlap (0.004). In total, SR and CON accounted for approximately 70% of the genetic and 20% of the environmental covariation between MDD and AUD. CONCLUSIONS This is the first study to demonstrate that negative emotionality and behavioral control confer risk for the co-occurrence of MDD and AUD via genetic factors. These findings are consistent with the aims of NIMHs RDoC proposal to elucidate how transdiagnostic risk factors drive psychopathology.

Age of initiation and substance use progression: A multivariate latent growth analysis.

An individual’s age at first substance use may be associated with their risk for progression toward heavier substance involvement. To our knowledge, however, no studies within nationally representative samples have examined the relation between the timing of initiation and progression in use of multiple substances. The present study employed a sample of 9,421 participants from the National Longitudinal Study of Adolescent to Adult Health who reported on their ages of tobacco, alcohol, and cannabis initiation; frequency of tobacco, alcohol, and cannabis use; and quantity of tobacco and alcohol use across 4 waves. We fit latent growth models to examine (a) associations between the age of initiation and initial status and rate of change in substance involvement, and (b) the degree to which the timing of first substance use accounted for differences in trajectories. There were significant relations between all ages of initiation and rates of change in tobacco (&bgr;s = −0.21 to −0.31, ps < .01) and alcohol use frequency (&bgr;s = 0.14 to 0.31, ps < .001), age of cannabis initiation and rate of change in tobacco use quantity (&bgr; = 0.23, p < .01), and age of tobacco initiation and rate of change in cannabis use frequency (&bgr; = −0.14, p < .01). After adjusting for age of initiation, significant associations were observed between trajectories for tobacco and alcohol (r = .43, p < .0001) and alcohol and cannabis (r = .20, p < .05). Results highlight differences in within- and cross-substance relations between the age of initiation and rate of change in use across substances. They suggest that differences in substance use trajectories are partly accounted for by age at first use.

Investigating Progression in Substance Use Initiation Using a Discrete-Time Multiple Event Process Survival Mixture (MEPSUM) Approach

The order and timing of substance initiation have significant implications for later problematic patterns of use. Despite the need to study initiation from a multivariate framework, survival analytic methods typically cannot accommodate more than two substances in one model. The discrete-time multiple event process survival mixture (MEPSUM) model represents an advance by incorporating more than two outcomes and enabling establishment of latent classes within a multivariate hazard distribution. Employing a MEPSUM approach, we evaluated patterns of tobacco, alcohol, and cannabis initiation in the National Longitudinal Study of Adolescent to Adult Health (N = 18,923). We found four classes that differed in their ages and ordering of peak initiation risk. Demographics, externalizing psychopathology, and personality significantly predicted class membership. Sex differences in the association between delinquency and initiation patterns also emerged. Findings support the utility of the MEPSUM approach in elucidating developmental pathways underlying clinically relevant phenomena.

Modern Advances in Genetic Testing: Ethical Challenges and Training Implications for Current and Future Psychologists

The ethical implications for psychological practice of genetic testing are largely unexplored. Predictive testing can have a significant impact on health and well-being, and increasing numbers of individuals with knowledge of their risk for various disorders are likely to present for psychotherapy. In addition, more people will struggle with the decision of whether to obtain information regarding their genetic material. Psychologists will need to have the appropriate knowledge and clinical skills to effectively counsel this population. This article highlights the relevant ethical issues surrounding psychological treatment of individuals pursuing or considering undergoing genetic testing. These issues are extended to psychologists working in research, education, and policy domains. Recommendations for graduate training programs to facilitate current and future practitioner competence are also discussed.