Gillespie NA, Whitfield JB, Williams B, Heath AC, Martin NG. The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression. Psychol Med 35: 101-111

Department of Psychiatry, Washington University in St. Louis, San Luis, Missouri, United States
Psychological Medicine (Impact Factor: 5.94). 02/2005; 35(1):101-11. DOI: 10.1017/S0033291704002727
Source: PubMed


Serotonin is a good candidate for major depression. We attempted to replicate the study by Caspi and colleagues [Science (2003) 301, 386-389] which reported a significant interaction between serotonin transporter (5-HTTLPR) genotype and stressful life events when predicting major depression.
We typed the serotonin promoter 5-HTTLPR gene in 1206 male and female twins aged 19-78 years (mean = 39, S.D. = 11). A DSM-IV diagnosis of major depression was available for 1199 twins. Most of these twins had participated in a 1988-1990 study which included a stressful life events inventory and self-report measure of depression based on the SCL-90 and DSSI/sAD. Complete 5-HTT genotype and life events data, self-report symptoms and major depression diagnoses were available for 1091 subjects. We regressed categorical and ordinal measures of depression onto stressful life events and genotype.
There were significant main effects for stressful life events but there was no evidence for any effect of 5-HTT genotype, nor a genotype x stressful life event interaction.
Regardless of whether our results were based on binary logistic or ordinal regression analyses we found no evidence to support a main effect of 5-HTTLPR, or an interaction between the 5-HTTLPR genotype and stressful life events on major depression, Only 20 % of our subjects were aged below 30 years. It is possible that the effect reported by Caspi and colleagues is specific to young people, in which case our study has much less power in this age group.

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    • "The majority of studies assessed the allelic effect (number of S alleles), but a few reported a genotypic effect (S/S, S/L vs. L/L or, alternatively, S/S vs. S/L, L/L) (Cervilla et al. 2007; Grabe et al. 2005; Kendler et al. 2005). Moreover, several studies modeled the interactions with SLEs on a cumulative count of stressors (Gillespie et al. 2005; Kim et al. 2007; Surtees et al. 2006), whereas others modeled SLEs by level of implied or measured stressfulness (Kendler et al. 2005; Ritchie et al. 2009). "
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    ABSTRACT: Depending on genetic sensitivity to it, stress may affect depressive symptomatology differentially. Applying the stress-diathesis hypothesis to older adults, we postulate: (1) recent stress will associate with increased depressive symptoms levels and (2) this effect will be greater for individuals with at least one short allele of the serotonin transporter gene promoter region (5-HTTLPR). Further, we employ a design that addresses specific limitations of many prior studies that have examined the 5-HTTLPR x SLE relation, by: (a) using a within-person repeated-measures design to address fluctuations that occur within individuals over time, increase power for detecting GxE, and address GE correlation; (b) studying reports of exogenous stressful events (those unlikely to be caused by depression) to help rule out reverse causation and negativity bias, and in order to assess stressors that are more etiologically relevant to depressive symptomatology in older adults. The sample is drawn from the Health and Retirement Study, a U.S. population-based study of older adults (N=28,248; mean age = 67.5; 57.3% female; 80.7% Non-Hispanic White, 14.9% Hispanic/Latino, 4.5% African American; genetic subsample = 12,332), from whom measures of depressive symptoms and exogenous stressors were collected biannually (1994-2010). Variation in the 5-HTTLPR was characterized via haplotype, using two single nucleotide polymorphisms (SNPs). Ordered logit models were constructed to predict levels of depressive symptoms from 5-HTTLPR and stressors, comparing results of the most commonly applied statistical approaches (i.e., comparing allelic and genotypic models, and continuous and categorical predictors) used in the literature. All models were stratified by race/ethnicity. Overall, results show a main effect of recent stress for all ethnic groups, and mixed results for the variation in 5-HTTLPRxStress interaction, contingent upon statistical model used. Findings suggest there may be a differential effect of stressors and 5-HTTLPR on depressive symptoms by ethnicity, but further research is needed particularly when using a haplotype to characterize variation in 5-HTTLPR in population-based sample with a diverse ethnic composition.
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    • "This has led to the hypothesis that neurogenesis and neuronal differentiation may be important factors in the recovery from depressive episodes (Kempermann and Kronenberg, 2003). Stressful life events and chronic stress can lead to depression (Kendler et al., 2000; Mello et al., 2003; Gillespie et al., 2005). Therefore, stress paradigms are often used to model depression-like behavior in animals . "
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    • "In our study, we only included cases that followed all the inclusion requirements, and cases with any deviation from our criteria were excluded. The excluded papers included 13 studies that were not for geriatric depression [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19], 3 brief reports or reviews [20] [21] [22] and 1 that is on Alzheimer's disease related depression [23]. We also excluded 3 studies that contained cases of unclear diagnosis of depression [24] [25] [26]. "
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