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To the Editor: We have some concerns with the meta-analysis by Dr Risch and colleagues,¹ which examined the role of 5-HTTLPR in moderating the relationship between stress and depression. We agree with the authors that blanket acceptance of a robust and universal interaction between 5-HTTLPR and stress is unwarranted, and it is premature to translate this into clinical and forensic settings. However, the authors concluded that the original finding was not confirmed, despite numerous independent positive reports in the literature. Other conclusions should be considered.

First, the studies included in the meta-analysis had notable heterogeneity in measurement of both environment (life events) and outcome (depression). Numerous sources of error measurement, such as recall bias, vaguely worded questions or anchors, and rater bias, can reduce the precision of measurement. Approximately 73% of the participants in this meta-analysis came from cross-sectional/retrospective studies, often using brief assessments, phone assessments, or both. Examples of . . . [Full Text of this Article]

Francis E. Lotrich, MD, PhD
lotrichfe@upmc.edu
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania

Eric Lenze, MD
Washington University
St Louis, Missouri

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