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  • Title: Serotonin transporter gene moderates childhood maltreatment's effects on persistent but not single-episode depression: replications and implications for resolving inconsistent results.
    Author: Uher R, Caspi A, Houts R, Sugden K, Williams B, Poulton R, Moffitt TE.
    Journal: J Affect Disord; 2011 Dec; 135(1-3):56-65. PubMed ID: 21439648.
    Abstract:
    BACKGROUND: Genetic and environmental factors shape life-long vulnerability to depression, but most gene-environment interaction (G×E) research has focused on cross-sectional assessments rather than life-course phenotypes. This study tests the hypothesis that the G×E involving the length polymorphism in the serotonin-transporter-gene-linked-promoter-region (5-HTTLPR) and childhood maltreatment is specific to depression that runs a persistent course in adulthood. METHODS: The hypothesis is tested in two cohorts. Men and women in the Dunedin Study (N=847), New Zealand, followed to age 32 years with 96% retention and women in the E-Risk Study (N=930), England, followed to age 40 years with 96% retention. Diagnoses of past-year major depressive episode were established at four separate assessments. Depression diagnosed on two or more occasions was considered persistent. RESULTS: In both cohorts, statistical tests of gene-environment interactions showed positive results for persistent depression but not single-episode depression. Individuals with two short 5-HTTLPR alleles and childhood maltreatment had elevated risk of persistent but not single-episode depression. LIMITATIONS: Some cases of recurrent depression may have been misclassified as single-episode due to non-contiguous assessment windows, but this would have a conservative effect on the findings. Chronic and recurrent depression could not be reliably distinguished due to non-contiguous periods of assessment. Therefore, the term persistent depression is used to describe either chronic or recurrent course. CONCLUSIONS: The specific effect on persistent depression increases the significance of this G×E for public health. Research that does not distinguish persistent course may underestimate G×E effects and account for some replication failures in G×E research.
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