The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update

Abstract

An updated review of 34 human observational studies indicates that the length polymorphism of the serotonin transporter gene moderates the effect of environmental adversity in the development of depression. This finding depends on the use of contextual or objective methods to assess environmental adversity and is attenuated when self-report instruments are used. Inconsistent findings in male adolescents suggest a developmental stage and sex-specific protective mechanism. These systematic relationships between method and results should be followed up to specify causal mechanisms leading to depression.

Interaction of Serotonin Transporter Gene-Linked Polymorphic Region and Stressful Life Events Predicts Cortisol Stress Response

“…However, when the focus was on SLE that had occurred during the first 5 years of life (SLE-5), there was a significant interaction between 5-HTTLPR genotype and SLE, but only in the younger adults, not in children (no SLE-5 data were available for older adults). Thus, this study is consistent with the hypothesis (Lewis et al, 2010;Uher and McGuffin, 2008) that age but also SLE assessment may be critical variables in gene-environment interactions involving 5-HTTLPR genotype (Uher and McGuffin, 2008;Uher and McGuffin, 2010). Future work will also need to address why significant G Â E interactions were absent in adolescents but present in younger adults.…”

“…The existing literature on gene-environment interactions for 5-HTTLPR genotype and life stress has produced conflicting results, possibly due to methodological heterogeneity across studies with respect to subject recruitment and life stress assessment (Uher and McGuffin, 2008;Uher and McGuffin, 2010). We have now conducted the first study to assess such a gene-environment interaction across multiple age cohorts, using a consistent and highly sensitive life stress assessment methodology, and a quantitatively measured biologically based endophenotype.…”

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project

“…37,38 Researchers remain divided on whether the genetic should be detected before testing for interactions. 39 In our analyses of the GENDEP data, we detected both a main effect of the 5-HTTLPR 16 and SLEs and their interaction on response to escitalopram.…”

Letter to the Editor: Bias in the measurement of bias. Letter regarding ‘Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression’

“…Karg et al (2011) show that differences between the negative meta-analyses and theirs are due to paper selection, not meta-analytic technique. Papers selected for their statistically homogeneous designs tend to have methodological flaws including retrospective lifetime stress and depression assessment (Moffitt & Caspi, 2014) leading to confounding (Uher & McGuffin, 2010). Moreover, Karg et al (2011) show that reports with more robust measures of stress (interview and Zhang (2009a) 'In addition, the individuals carrying the L/L genotype of 5-HTTLPR could be susceptible to MDD when exposed to negative life events and MDD in the Chinese population' 5-HTTLPR, Serotonin transporter gene; RD, risk difference; CI, confidence interval; BDNF, brain-derived neurotrophic factor; OR, odds ratio; SNP, single nucleotide polymorphism; MDD, major depressive disorder; G × E, gene-environment interaction.…”