European-American Subsample Research Articles

Characteristics of youth with reported family history of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort

Little is known about the impact of family history of psychosis on youth from community samples. To fill this gap, we compared youth with a first-degree relative with psychosis spectrum symptoms (i.e. family history of psychosis spectrum symptoms, FHPS) to youth without FHPS in a cross-sectional analysis of the Philadelphia Neurodevelopmental Cohort (PNC). The PNC is a racially diverse community sample of 9498 youth ages 8–21 years old, of whom 8928 completed the Family Interview for Genetic Studies to determine FHPS status. Polygenic risk score for schizophrenia (PRSS) was available for a subsample of 4433 European Americans. FHPS youth (n = 489) constituted 5.5% of the analytic sample. After adjusting for environmental risk factors (sociodemographic variables and traumatic stressful events), FHPS youth had lower functioning on the Children's Global Assessment Scale and elevated psychosis spectrum, mood, externalizing, and fear symptoms compared to non-FHPS youth (all p < .001). In the European-American subsample, FHPS status was associated with poorer functioning and greater symptom burden in all four psychopathology domains (all p < .001), even after covarying for PRSS. Thus, ascertaining FHPS is important because it is uniquely associated with symptoms and functional impairment in community youth beyond PRS-S and the environmental risk factors we investigated. Future research identifying environmental causes of FHPS-associated impairment could inform the development of interventions for the broad array of symptoms observed in FHPS youth.

Polygenic risk, family cohesion, and adolescent aggression in Mexican American and European American families: Developmental pathways to alcohol use.

Poor family cohesion and elevated adolescent aggression are associated with greater alcohol use in adolescence and early adulthood. In addition, evocative gene-environment correlations (rGEs) can underlie the interplay between offspring characteristics and negative family functioning, contributing to substance use. Gene-environment interplay has rarely been examined in racial/ethnic minority populations. The current study examined adolescents' polygenic risk scores for aggression in evocative rGEs underlying aggression and family cohesion during adolescence, their contributions to alcohol use in early adulthood (n = 479), and differences between Mexican American and European American subsamples. Results suggest an evocative rGE between polygenic risk scores, aggression, and low family cohesion, with aggression contributing to low family cohesion over time. Greater family cohesion was associated with lower levels of alcohol use in early adulthood and this association was stronger for Mexican American adolescents compared to European American adolescents. Results are discussed with respect to integration of culture and racial/ethnic minority samples into genetic research and implications for alcohol use.

Do Family-Level Factors Associated With Bullying Perpetration and Peer Victimization Differ by Race? Comparing European American and African American Youth.

Patterns of-and correlates associated with-bullying perpetration and peer victimization have received widespread research attention. Somewhat less research has considered how protective factors in the parental domain help to buffer against both adverse behaviors. And perhaps more importantly, even less research has considered potential racial differences in the manner in which family-level variables relate to both bullying perpetration and peer victimization. Using a nationwide sample of adolescents, the present study examines (a) how parent/guardian support, mother's parental monitoring, father's parental monitoring, and family satisfaction buffer against bullying perpetration and peer victimization; and (b) whether these relationships vary across race. Data are derived from the 2009 to 2010 Health Behavior in School-Aged Children study in the United States. A total of 8,998 adolescents were included in the study sample, which consisted of 6,521 European Americans and 2,477 African Americans. Findings show that both European American and African American youth who received parental/guardian support were less likely to report being bullied. Among both African American and European American sub-samples, results showed that mother's parental monitoring was negatively associated with both bullying perpetration and peer victimization. Father's parental monitoring was negatively associated with peer victimization and bullying perpetration for European Americans only. Both European and African American youth who reported being satisfied with their family were less likely to report being bullied while European American youth who reported higher family satisfaction were less likely to engage in bullying. In sum, several family variables help to buffer against both bullying perpetration and peer victimization, but for the most part these relationships are race-invariant.

Balancing risk and benefit in heavy drinkers treated with topiramate: implications for personalized care.

Despite topiramate's ability to reduce heavy drinking, its adverse effects may limit its clinical utility. To evaluate the risks and benefits of topiramate, we reanalyzed data from a completed trial of the medication in 138 heavy drinkers whose goal was to reduce their drinking to safe levels. We used the number of patients who had no heavy drinking days during the last 4 weeks of treatment to calculate topiramate's number needed to treat (NNT). To balance the risks and benefits of topiramate, we adjusted the NNT using 2 different levels of adverse event severity: moderate or greater (NNT-AEmod+) and severe or greater (NNT-AEsev+). This measure helps to guide the clinical use of topiramate in heavy drinkers by incorporating both its beneficial and adverse effects in a single measure. Because a polymorphism (rs2832407) in the gene encoding a kainate receptor subunit appears to moderate topiramate's effects in heavy drinkers, we repeated the analyses based on rs2832407 genotype (C-homozygote vs A-allele carrier) in the European American subsample (n = 122). Overall, the NNT for topiramate was 5.29, the NNT-AEmod+ was 7.52, and the NNT-AEsev+ was 6.12. Among European Americans with the rs2832407*CC genotype, the NNT was 2.28, the NNT-AEmod+ was 2.63, and the NNT-AEsev+ was 2.56. In contrast, for rs2832407*A-allele carriers, the NNT was 180.00, the NNT-AEmod+ was 322.16, and the NNT-AEsev+ was 217.45. In this sample of heavy drinkers, topiramate had a clinically important treatment effect that was most evident in European Americans with the rs2832407*CC genotype. In that group, in particular, it had a robust treatment effect, even when adjusted for adverse events. ClinicalTrials.gov identifier: NCT00626925.

Genetic and environmental contributions to initiation of cigarette smoking in young African-American and European-American women

BackgroundDistinctions in the relative contributions of genetic and environmental factors to initiation of cigarette smoking may explain, in part, the differences between African Americans and European Americans in the prevalence of smoking. The current investigation is the first to compare heritable and environmental influences on smoking initiation between African-American and European-American women. MethodsData were drawn from Missouri Adolescent Female Twin Study participants and female Missouri Family Study participants (n=4498; 21% African-American, the remainder European-American). Mean ages at first and last assessments were 17.0 (SD=3.5) and 24.0 (SD=3.2), respectively. Twin-sibling modeling was conducted to estimate the proportion of variance in smoking initiation (i.e., ever trying a cigarette) attributable to additive genetic, shared environmental, special twin environmental, and unique environmental factors. ResultsAdditive genetic influences accounted for approximately half of the variance in smoking initiation in both African-American and European-American women. In the African-American subsample, the remaining variance was attributable primarily to unique environmental factors (46%; 95% CI: 28–71%). In the European-American subsample, only 12% (95% CI: 8–16%) of the variance was attributable to unique environmental factors, with the remainder accounted for by shared environmental (13%; 95% CI: 0–41%) and special twin environmental (24%; 95% CI: 0–52%) factors. ConclusionsThe estimated heritability of smoking initiation is substantial and nearly identical for African-American and European-American women, but the type of environmental factors that contribute to risk differ by race/ethnicity. Whereas the primary environmental influences on European-American women's smoking initiation are at the family level, those that impact African-American women's smoking initiation are primarily individual-specific.

Posttreatment effects of topiramate treatment for heavy drinking.

We examined whether the effects of topiramate and a single nucleotide polymorphism (rs2832407) in GRIK1, which encodes a kainate receptor subunit, persisted following a 12-week, placebo-controlled trial in 138 heavy drinkers with a treatment goal of reduced drinking. During treatment, topiramate 200mg/d significantly reduced heavy drinking days and increased the frequency of abstinent days (Am J Psychiatry, 2014, 171:445). In the European-American (EA) subsample (n=122), rs2832407 moderated the treatment effect on heavy drinking. Patients were re-interviewed 3 and 6months after the end of treatment. During treatment, we obtained 92.4% of drinking data, with 89.1 and 85.5% complete data at the 3- and 6-month follow-up visits, respectively. We examined 4 outcomes over time in the overall sample and the EA subsample: percent heavy drinking days (PHDD), percent days abstinent (PDA), serum γ-glutamyl transpeptidase (GGTP) concentration, and a measure of alcohol-related problems. In the full sample, the lower PHDD and higher PDA seen with topiramate treatment were no longer significant during follow-up. Nonetheless, the topiramate-treated patients had lower alcohol-related problem scores during treatment and both follow-up periods. Further, in the EA subsample, the greater reduction in PHDD seen with topiramate treatment in rs2832407*C-allele homozygotes persisted throughout follow-up, with no significant effects in A-allele carriers. A reduction in GGTP concentration was consistent with the reduction in heavy drinking, but did not reach statistical significance. There are persistent therapeutic effects of topiramate in heavy drinkers, principally in rs2832407*C-allele homozygotes.

Topiramate's reduction of body mass index in heavy drinkers: lack of moderation by a GRIK1 polymorphism.

Topiramate, which interacts with multiple neurotransmitter and enzyme systems, is approved by the Food and Drug Administration to treat seizure disorder, prevent migraine, and (in combination with phentermine) reduce weight. Topiramate has also been shown in multiple studies to reduce heavy drinking. The authors found that topiramate 200 mg/day significantly reduced heavy drinking in heavy drinkers with a treatment goal of reduced drinking (Kranzler et al., 2014). Further, in the European American (EA) subsample (n = 122), a single nucleotide polymorphism (rs2832407) in GRIK1, which encodes the GluK1 subunit of the kainate receptor, moderated the effect on heavy drinking days. Here the authors examined the effects of topiramate on body mass index (BMI) and the moderating effect of rs2832407 in the EA subsample from Kranzler et al. (2014). Across the 12 weeks of treatment, BMI was reduced by 1.2 kg/m2 (p < .001) in the topiramate group but was unchanged in the placebo group. There was no evidence of moderation by rs2832407 of topiramate's effects on BMI. Controlling for changes in drinking and other potential confounders did not alter the findings. These results suggest that the effect of topiramate on drinking behavior, in which the GluK1-containing kainate receptor appears to play a key role, can be dissociated from its effect on weight, the specific mechanism of which remains to be determined.

Topiramate treatment for heavy drinkers: moderation by a GRIK1 polymorphism.

Topiramate has been shown to reduce drinking and heavy drinking in individuals with alcohol dependence whose goal was to stop drinking. The authors evaluated the efficacy and tolerability of topiramate in heavy drinkers whose treatment goal was to reduce drinking to safe levels. A total of 138 individuals (62.3% men) were randomly assigned to receive 12 weeks of treatment with topiramate (N=67), at a maximal daily dose of 200 mg, or matching placebo (N=71). Both groups received brief counseling to reduce drinking and increase abstinent days. It was hypothesized that topiramate-treated patients would be better able to achieve these goals, and it was predicted that based on prior research, the effects would be moderated by a single nucleotide polymorphism (rs2832407) in GRIK1, encoding the kainate GluK1 receptor subunit. The rate of treatment completion was 84.9% and equal by treatment group. Topiramate treatment significantly reduced heavy drinking days and increased abstinent days relative to placebo. Patients receiving topiramate also had lower concentrations of the liver enzyme γ-glutamyl transpeptidase and lower scores on a measure of alcohol-related problems than the placebo group. In a European American subsample (N=122), topiramate's effect on heavy drinking days was significantly greater than that for placebo only in rs2832407 C-allele homozygotes. These findings support the use of topiramate at a daily dose of 200 mg to reduce heavy drinking in problem drinkers. The moderator effect of rs2832407, if validated, would facilitate the identification of heavy drinkers who are likely to respond well to topiramate treatment and provide an important personalized treatment option. The pharmacogenetic findings also implicate the kainate receptor in the mechanism of topiramate's effects on heavy drinking.

DSM-5 cannabis use disorder: A phenotypic and genomic perspective

BackgroundWe explore the factor structure of DSM-5 cannabis use disorders, examine its prevalence across European- and African-American respondents as well as its genetic underpinnings, utilizing data from a genome-wide study of single nucleotide polymorphisms (SNPs). We also estimate the heritability of DSM-5 cannabis use disorders explained by these common SNPs. MethodsData on 3053 subjects reporting a lifetime history of cannabis use were utilized. Exploratory and confirmatory factor analyses were conducted to create a factor score, which was used in a genome-wide association analysis. p-values from the single SNP analysis were examined for evidence of gene-based association. The aggregate effect of all SNPs was also estimated using Genome-Wide Complex Traits Analysis. ResultsThe unidimensionality of DSM-5 cannabis use disorder criteria was demonstrated. Comparing DSM-IV to DSM-5, a decrease in prevalence of cannabis use disorders was only noted in European-American respondents and was exceedingly modest. For the DSM-5 cannabis use disorders factor score, no SNP surpassed the genome-wide significance testing threshold. However, in the European-American subsample, gene-based association testing resulted in significant associations in 3 genes (C17orf58, BPTF and PPM1D) on chromosome 17q24. In aggregate, 21% of the variance in DSM-5 cannabis use disorders was explained by the genome-wide SNPs; however, this estimate was not statistically significant. ConclusionsDSM-5 cannabis use disorder represents a unidimensional construct, the prevalence of which is only modestly elevated above the DSM-IV version. Considerably larger sample sizes will be required to identify individual SNPs associated with cannabis use disorders and unequivocally establish its polygenic underpinnings.

Social constraints, genetic vulnerability, and mental health following collective stress

A repeat-length polymorphism of the serotonin promoter gene (5-HTTLPR) has been associated with depression and posttraumatic stress disorder (PTSD) in trauma-exposed individuals reporting unsupportive social environments. We examine the contributions of the triallelic 5-HTTLPR genotype and social constraints to posttraumatic stress (PTS) symptoms in a national sample following the September 11, 2001 (9/11) terrorist attacks. Saliva was collected by mail from 711 respondents (European American subsample n = 463) of a large national probability sample of 2,729 adults. Respondents completed web-based assessments of pre-9/11 mental and physical health, acute stress 9 to 23 days post-9/11, PTS symptoms, and social constraints on disclosure regarding fears of future terrorist attacks 2-3 years post-9/11. Social constraints were positively associated with PTS symptoms 2-3 years post-9/11. The triallelic 5-HTTLPR genotype was not directly associated with PTS symptoms, but it interacted with social constraints to predict PTS symptoms 2-3 years post-9/11: Social constraints were more strongly associated with PTS symptoms for individuals with any s/lg allele than for homozygous la/la individuals. Constraints on disclosing fears about future terrorism moderate the 5-HTTLPR genotype-PTS symptom association even when indirectly exposed to collective stress.

Anxiety, Alexithymia, and Depression as Mediators of the Association between Childhood Abuse and Eating Disordered Behavior in African American and European American Women

This study evaluated structural equation models of the associations among family functioning, childhood abuse, depression, anxiety, alexithymia, and eating disorder symptomatology in a sample of 412 European American and 192 African American female undergraduates. Additionally, the specific roles of anxiety, depression, and alexithymia as mediators were assessed. Each of these variables was a significant mediator of the association between childhood abuse and disordered eating. Finally, a test of invariance between the African American and European American subsamples was significant, highlighting the need for additional cross-cultural eating disorder research.