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Lilly-Molecular Psychiatry Award, Winner

Gene–environment interaction analysis of serotonin system markers with adolescent depression

Abstract

We report analyses from a study of gene–environment interaction in adolescent depression. The sample was selected from 1990 adolescents aged 10–20 years: those with depression symptoms in the top or bottom 15% were identified and divided into high or low environmental risk groups. DNA was obtained from 377 adolescents, representing the four quadrants of high or low depression and high or low environmental risk. Markers within, or close to, each of the serotonergic genes 5HTT, HTR2A, HTR2C, MAOA (monoamine oxidase type A) and tryptophan hydroxylase (TPH) were genotyped. Environmental risk group was a nonsignificant predictor and sex was a significant predictor of the depression group. HTR2A and TPH significantly predicted the depression group, independent of the effects of sex, environmental risk group and their interaction. In addition, there was a trend for an effect of 5HTTLPR, which was significant in female subjects. Furthermore, there was a significant genotype–environmental risk interaction for 5HTTLPR in female subjects only, with the effect being in the same direction as another recent study, reaffirming that an important source of genetic heterogeneity is exposure to environmental risk.

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Acknowledgements

This research was supported by a project grant from the WT Grant Foundation and by a Career Development Award from the British Medical Research Council to the first author. The GENESiS project was supported by Grant G9901258 from the UK Medical Research Council. We thank the families of the G1219 study for their time, and Matthew Nash, Abram Sterne, Richard Williamson and Maria Napolitano for their contributions to the project.

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Correspondence to T C Eley.

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Eley, T., Sugden, K., Corsico, A. et al. Gene–environment interaction analysis of serotonin system markers with adolescent depression. Mol Psychiatry 9, 908–915 (2004). https://doi.org/10.1038/sj.mp.4001546

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