Serotonin transporter gene moderates childhood maltreatment's effects on persistent but not single-episode depression: replications and implications for resolving inconsistent results.
- Authors
- Uher, Rudolf; Caspi, Avshalom; Houts, Renate; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Moffitt, Terrie E
- Year
- 2011
- Journal
- Journal of affective disorders
- PMID
- 21439648
- DOI
- 10.1016/j.jad.2011.03.010
- PMCID
- PMC3752793
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.
Proportion of individuals with persistent depression (panels A, B) and single-episode depression (panels C, D) by childhood maltreatment and serotonin transporter genotype in the Dunedin (panels A, C) and E-Risk (panels B, D) cohorts. The y axis shows the probability of being diagnosed with past year major depression at two or more of the four assessments by level of childhood maltreatment and 5-HTTLPR genotype (LL, SL, and SS). In the Dunedin cohort, maltreatment is a composite trichotomous measure based on observer ratings, parent reports and self-reports (0 = None, 1 = Probable, 2 = Definite). In the E-risk study, maltreatment is a rounded average score on the Childhood Trauma Questionnaire (0 = None, 1 = Mild, 2 = Moderate, 3 = Severe). The number of individuals included in each subgroup is given above each bar.
LLM interpretation
This figure consists of four bar charts (panels A-D) showing the probability of persistent depression (A, B) and single-episode depression (C, D) across the Dunedin and E-Risk cohorts. The x-axes represent levels of childhood maltreatment (0 to 3), grouped by 5-HTTLPR genotype (LL, SL, and SS), with the y-axis indicating the probability of diagnosis. In panels A and B, the probability of persistent depression generally increases with higher levels of maltreatment, with the most pronounced increase observed in the SS genotype group.
Proportion of individuals with past-year diagnosis of major depression at each assessment in the Dunedin and E-Risk cohorts by level of childhood maltreatment and serotonin transporter genotype. Dunedin: Time 1 = age 18, Time 2 = age 21; Time 3 = age 26, Time 4 = age 32; E-Risk: Time 1 = mean age 33, Time 2 = mean age 35; Time 3 = mean age 38, Time 4 = mean age 40; 5-HTTLPR genotype is marked by “LL”, “LS” and “SS” above each group of bars. In the Dunedin cohort, maltreatment is a composite trichotomous measure based on observer ratings, parent reports and self-reports (0 = None, 1 = Probable, 2 = Definite). In the E-risk study, maltreatment is a rounded average score on the Childhood Trauma Questionnaire (0 = None, 1 = Mild, 2 = Moderate, 3 = Severe). For the number of individuals included in each subgroup, please see Fig. 1.
LLM interpretation
This figure consists of eight panels of bar charts showing the proportion of individuals with a past-year diagnosis of depression across four time points for the E-Risk and Dunedin cohorts. The x-axes represent levels of childhood maltreatment (0–3 for E-Risk; 0–2 for Dunedin), and the y-axes represent the proportion of depression. Data are grouped by 5-HTTLPR genotype (LL, SL, SS), generally showing an increase in depression proportions as the level of maltreatment increases, particularly within the SS genotype group.
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| Title | Year | PMID |
|---|---|---|
| Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. | 2018 | 28373689 |
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