Frances L. Wang

Genetic Associations with Performance on a Behavioral Measure of Distress Intolerance

Both theory and empirical evidence support possible associations between two candidate genetic polymorphisms (SLC6A4 5-HTTLPR l/s and COMT Val(158)Met--rs4680 variants) and emotion-regulation difficulties. One particular form of emotion-regulation difficulty, distress intolerance, has been measured using a behavioral assessment in youth; data indicate a relationship with poor psychological functioning. No prior study has investigated genetic influences on emotion-regulation difficulties in youth. As part of a larger longitudinal study on adolescent risk behaviors, 218 10-14 year-old youths from the metropolitan Washington, D.C., area completed a measure of distress intolerance, the Behavioral Indicator of Resilience to Distress (BIRD), and provided saliva samples for DNA extraction and genotyping. Results indicate that those with one or two copies of the s allele of the 5-HTTLPR polymorphism were more likely to perform poorly on the task (i.e., choose to quit) than were those homozygous for the l allele. Participants who were Val allele carriers of the COMT Val(158)Met polymorphism were also more likely to quit the task compared to Met homozygotes. A summative risk allele score was created to combine the two polymorphisms, and each risk allele was associated with a 1.75 fold increased likelihood of quitting the task. Exploratory analyses revealed that emotional abuse moderated the relationship between the 5-HTTLPR and BIRD performance, as well as the genetic risk allele and the BIRD. This is the first investigation of genetic predictors of a behavioral measure of tolerance to distress. Results suggest that distress tolerance is at least partially regulated by specific genetic variants. Implications are discussed.

The relationship between risk-taking propensity and the COMT Val 158 Met polymorphism among early adolescents as a function of sex

Although adolescents frequently engage in a variety of risky behaviors, much remains unknown about the specific etiologies of such tendencies. Candidate genetic variants, such as the COMT Val(158)Met polymorphism, may be related to risk-taking propensity, particularly as this variant is linked to functional enzymatic differences influencing dopamine function in regions including the prefrontal cortex. The present study aimed to examine the COMT Val(158)Met variant in relation to risk-taking propensity in a community sample of youth. As part of a larger longitudinal study on adolescent risk behaviors, 223 youths (average age 11.3 years) from the metropolitan Washington D.C. area completed a measure of risk-taking propensity, the Balloon Analog Risk Task-Youth Version (BART-Y), and provided saliva samples for DNA extraction and genotyping. Results indicate that females, but not males, who are carriers of the COMT 158Met allele had higher risk-taking propensity scores on the BART-Y compared to Val homozygotes. Analyses were also conducted in the 111 European American participants, and results were consistent with those of the full sample analyses. This study represents the first investigation of a genetic substrate of risk-taking propensity, measured by a behavioral task, in youth. Results should be taken as quite preliminary, given the small sample. Implications are discussed.

The Interactive Effects of Effort to Regulate Alcohol Use, Anxiety Disorders, and Affective Disorders on Long-Term Remission from Alcohol Dependence

Objective: This study examined how effort to regulate alcohol use may interact with anxiety and affective disorders to influence long-term remission from alcohol dependence. Method: Using participants (n = 96; 73% male; 66% children of alcoholics; 71% non-Hispanic Caucasian; 26% Hispanic) from a high-risk community study who showed evidence of recovered alcohol dependence at baseline, this study examined whether effort to regulate alcohol use at the baseline assessment significantly influenced the likelihood of maintaining remission from alcohol dependence for a period of five years or more. This study also examined whether having an anxiety or affective disorder interacted with effort to regulate alcohol use. All analyses controlled for treatment history, baseline alcohol use, parent alcoholism, age and gender. Results: Results from logistic regressions showed that effort to regulate alcohol use had a significant unique main effect on long-term maintenance of remission from alcohol dependence. Having an affective and/or anxiety disorder did not have a significant main effect on the maintenance of remission. However, having an anxiety/affective disorder significantly moderated the influence of effort to regulate alcohol use such that the protective effect of effort to regulate use on remission from alcohol dependence was only significant for those without an affective or anxiety disorder. Conclusions: Individuals who try harder to limit their drinking are more likely to maintain long-term remission from alcohol dependence. However, affective and anxiety disorders may undermine the protective effect of effort to regulate alcohol use on long-term remission.

Negative Urgency Mediates the Relation Between Genetically Influenced Serotonin Functioning and Alcohol Problems

Serotonin (5-HT) functioning is associated with alcohol problems. However, the mechanisms underlying this association remain unclear. In the current study the authors tested whether five separate dimensions of impulsivity (UPPS-P) mediated the relation between a polygenic score indexing 5-HT functioning and alcohol problems and whether any of these paths were moderated by age. Results showed that a 5-HT polygenic score predicted alcohol problems indirectly through negative urgency, but not any other facet of impulsivity. The 5-HT polygenic score also directly predicted alcohol problems. No age moderation was found. Findings suggest that negative urgency might be one important mechanism underlying the relation between genetically influenced 5-HT functioning and alcohol problems. However, genetically influenced 5-HT functioning likely influences alcohol problems through additional mechanisms. More broadly, results suggest that the previously observed transdiagnostic nature of 5-HT functioning on diverse types of psychopathology might be, in part, explained by its effect on negative urgency.

Erratum to: Mechanisms in the relation between GABRA2 and adolescent externalizing problems(Eur Child Adolesc Psychiatry, 10.1007/s00787-015-0703-7)

The published version of the paper has stated the coding direction of the ancestry factor scores incorrectly. Higher levels of the ancestry factor scores actually indicate higher levels of non-Hispanic Caucasian ancestry (not higher levels of Hispanic ancestry). Therefore, under the “Participants” section, it should state that the included participants had higher levels of non-Hispanic Caucasian ancestry when compared with excluded participants. Under the “Results” section, it should state that the Hispanic ancestry predicted higher T2 alcohol problems and hyperactive–inattentive symptoms.

Erratum to: Mechanisms in the relation between GABRA2 and adolescent externalizing problems

The published version of the paper has stated the coding direction of the ancestry factor scores incorrectly. Higher levels of the ancestry factor scores actually indicate higher levels of non-Hispanic Caucasian ancestry (not higher levels of Hispanic ancestry). Therefore, under the “Participants” section, it should state that the included participants had higher levels of non-Hispanic Caucasian ancestry when compared with excluded participants. Under the “Results” section, it should state that the Hispanic ancestry predicted higher T2 alcohol problems and hyperactive–inattentive symptoms.