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Appraisals of Stressful Life Events as a Genetically-Linked Mechanism in the Stress–Depression Relationship

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Abstract

Variation in the promoter region of the serotonin transporter gene (5-HTTLPR) has been linked to various cognitive-affective indices of stress sensitivity hypothesized to underlie vulnerability to depression. The current study examined the association of 5-HTTLPR with appraisals of naturally occurring acute life stressors in a community sample of 384 youth at elevated risk for depression due to oversampling for maternal depression. Interview measures administered at youth age 20 were used to assess subjective and objective (assigned by an independent rating team) appraisals of the negative impact of recent acute stressful life events. The presence of at least one S allele was associated with elevated subjective appraisals of the negative impact of acute stressors (P = 0.03). Consistent with an endophenotype perspective, support was found for a 5-HTTLPR-stress appraisals-depression mediation model both concurrently and longitudinally. Results indicate that enhanced stress sensitivity may act as an intermediate phenotype through which 5-HTTLPR affects risk for depression.

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Notes

  1. In an attempt to minimize the confounding influences of population stratification, analyses were conducted among Caucasians only (i.e., 93% of the genotyped sample). The significance and overall pattern of results were unaltered.

  2. Preliminary analyses were conducted in which subjective negative impact ratings were the dependent variable in a linear regression model and objective ratings were entered as a covariate. This method is similar analytically to the standardized residual approach employed here (Cole et al. 1998) and the pattern of results was equivalent across analyses. Thus, for ease of presentation, only results from analyses using residuals as the dependent variable are reported.

  3. We examined potential confounding effects of variability in the time elapsed between data collection points. Analyses showed that the length of the interval between assessments did not moderate the influence of appraisals (b = 0.02, SE = 0.05, P = 0.80) or 5-HTTLPR (b = 0.03, SE = 0.11, P = 0.82) on BDI. These results suggested that the varying length of time between assessments of the mediator and outcome was unlikely to bias parameter estimates.

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Acknowledgments

The authors greatly appreciate the assistance of Robyne LeBrocque, Cheri Dalton Comber, and Sascha Hardwicke (project coordinators) and their interview staff. We also thank staff of the Genetic Epidemiological Laboratory of the Queensland Institute of Medical Research: Professor Nick Martin (Head) for cooperation and access, Michael James and Leanne Ryan for 5-HTTLPR and rs25531 genotyping, and Megan Campbell and Dixie Statham who coordinated genetic data collection and analysis. Thanks also to the original MUSP principals, William Bor, MD, Michael O’Callaghan, MD, and Professor Gail Williams.

Conflict of interest

The authors report no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Psychology, University of California, Los Angeles, P.O. Box 951563, Los Angeles, CA, 90095-1563, USA

    Christopher C. Conway & Constance Hammen

  2. Psychology Service, VA San Diego Healthcare System, San Diego, CA, USA

    Emmanuel P. Espejo

  3. Genetic and Molecular Epidemiology Laboratories, Queensland Institute of Medical Research, Brisbane, Australia

    Naomi R. Wray

  4. School of Population Health, University of Queensland, Brisbane, Australia

    Jake M. Najman

  5. Department of Psychology, Emory University, Atlanta, GA, USA

    Patricia A. Brennan

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  1. Christopher C. Conway
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  2. Constance Hammen
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Correspondence to Christopher C. Conway.

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Conway, C.C., Hammen, C., Espejo, E.P. et al. Appraisals of Stressful Life Events as a Genetically-Linked Mechanism in the Stress–Depression Relationship. Cogn Ther Res 36, 338–347 (2012). https://doi.org/10.1007/s10608-011-9368-9

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