Abstract
We report results from the PREDICT-Gene case-control study nested in a prospective cohort designed to identify predictors of the onset of depression among adult primary-care attendees. We tested the potential gene-by-environment interaction between 5HTTLPR genotype at the serotonin transporter gene and previous exposure to threatening life events (TLEs) in depression. A total of 737 consecutively recruited participants were genotyped. Additional information was gathered on exposure to TLEs over a 6-month period, socio-demographic data and family history of psychological problems among first-degree relatives. Diagnoses of depression were ascertained using the Composite International Diagnostic Interview (CIDI) by trained interviewers. Two different depressive outcomes were used (ICD-10 depressive episode and ICD-10 severe depressive episode). Both the s/s genotype and exposure to increasing number of TLEs were significantly associated with depression. Moreover, the 5HTTLPR s/s genotype significantly modified the risk conferred by TLEs for both depressive outcomes. Thus, s/s homozygous participants required minimal exposure to TLE (1 TLE) to acquire a level of risk for depression that was only found among l/s or l/l individuals after significantly higher exposure to TLEs (two or more TLEs). The interaction was more apparent when applied to the diagnosis of ICD-10 severe depressive episode and after adjusting for gender, age and family history of psychological problems. Likelihood ratios tests for the interaction were statistically significant for both depressive outcomes (ICD-10 depressive episode: LR X2=4.7, P=0.09 (crude), LR-X2=6.4, P=0.04 (adjusted); ICD-10 severe depressive episode: LR X2=6.9, P=0.032 (crude), LR-X2=8.1, P=0.017 (adjusted)).
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Acknowledgements
We thank the PREDICT study Core Group members (Miguel Xavier, Igor Slav, Heidi-Ingrid Maaros, Jan Neelman, Francisco Torres-González, Irwing Nazareth and Michael King) for agreeing to include a genetic sub-study to their ongoing study. We also thank the three interviewers (Francisca Vidal, Nuria López and Ana Álvarez) and all nurses and general practitioners at all nine primary care centres in Málaga (Spain) for their collaboration and hard work in collecting most of the data. This study was co-funded by the fifth Framework Program of the European Commission, a grant from the Ministry of Education and Science (SAF-2004-01310) and by I+D+I Grant from the Ministry of Education and Science SAF2006-07192.
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Cervilla, J., Molina, E., Rivera, M. et al. The risk for depression conferred by stressful life events is modified by variation at the serotonin transporter 5HTTLPR genotype: evidence from the Spanish PREDICT-Gene cohort. Mol Psychiatry 12, 748–755 (2007). https://doi.org/10.1038/sj.mp.4001981
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DOI: https://doi.org/10.1038/sj.mp.4001981
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