Chunk #1 — Bias in a protocol for a meta-analysis of 5-HTTLPR, stress, and depression — Issue 1: “Primary Analysis Plan 2” to study lifetime depression does not allow for establishing temporal order between stress and depression
Primary Analysis Plan 2 in Culverhouse et al. [1] states that studies that measured stress and depression using lifetime measurement will be included in the meta-analysis. However, these studies should not be used in the forthcoming meta-analysis because using lifetime measures precludes establishing temporal order between a hypothesized cause and a hypothesized effect. The hypothesis in question is that individuals with an at-risk serotonin transporter genotype are likely to develop depression after life stress and in response to it. The minimal criterion for a valid test of this hypothesis is a set of measures that can unambiguously establish that the stress came before the depression. When using lifetime measures one cannot simply make the assumption that stress came before the depression, because there is a literature showing that individuals with depression tend to experience more stressful life events as a consequence of their mood disorder [3]. This well-known phenomenon is referred to in the literature as “stress generation” [4]. For example, depressed individuals have elevated rates of intimate partner violence and divorce. To use retrospective reports of lifetime depression in
