Genetic associations with performance on a behavioral measure of distress intolerance

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Abstract

Both theory and empirical evidence support possible associations between two candidate genetic polymorphisms (SLC6A4 5-HTTLPR l/s and COMT Val158Met – 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 Val158Met 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.

Section snippets

Subjects

This study employed data from a sample of early adolescents (n = 277) ages 9 to 13 at initial enrollment participating in a larger prospective study of behavioral, environmental, and genetic mechanisms of risk for HIV-related risk behaviors in youth. Follow-up assessments were conducted at yearly intervals for 2 consecutive years and are ongoing with additional assessments planned. The current study presents data from the first annual follow-up assessment (Wave 2) of the study. Permission to

Results

Descriptive statistics for independent variables are provided in Table 1. Of those with genotype data for 5-HTTLPR and COMT Val158Met (n = 218), 52.3% quit the BIRD task (n = 114), and the remaining 47.7% persisted on the task (n = 104). The BIRD was psychologically stressful, as indicated by a significant pre-post change in distress (t = 6.73, p < .001). However, pre-post change in distress in response to the task was unrelated to whether or not youth quit the BIRD (p > .50), indicating that

Discussion

Within the behavioral genetics literature there has been limited success in the identification of specific genes that predict psychiatric phenotypes, and investigations of potential intermediary phenotypes, such as the present study, may help in this line of research. The present study extends the literature by employing a behavioral task that reliably produced psychological stress, as indicated as pre-post changes in negative affect, to assess a potential intermediary phenotype (“distress

Limitations and future directions

An important caveat about the measurement of distress tolerance in the current study is important to note; specifically the use of a behavioral task versus self-report. Recent findings have indicated that there are inconsistencies in the measurement of this construct with respect to self-report versus behavioral tasks (Levro et al., 2010, Marshall-Berenz et al., 2010, McHugh et al., 2011) and accordingly speculations that these assessment methods capture different aspects of distress

Role of funding

This work was supported by R01 DA018647-02S1, RL1 AA017539, P20 DA027844, and US- HD055885. The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Dr. Amstadter is supported by US-NICHD HD055885, Dr. MacPherson is supported by DA018730-04A1, DA029445, and K23DA023143-01, Dr. Daughters is supported by DA 022741, Dr. Danielson is supported by DA018686 and MH086313.

Contributors

Dr. Amstadter was responsible for statistical analyses and writing of the first draft of the manuscript. Drs. Lejuez, Daughters, and MacPherson designed the study. Ms. Reynolds and Wang collected the data. Drs. Potenza and Gelernter oversaw the genetics aim of the study. All authors approved the final manuscript and made contributions.

Conflict of interest

Dr. Potenza has consulted for and advised Boehringer Ingelheim; has received research support from the National Institutes of Health, Veteran’s Administration, Mohegan Sun Casino, the National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and Forest Laboratories pharmaceuticals; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; has consulted for law

Acknowledgements

The authors have no additional acknowledgements to make at this time.

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