A validation of the diathesis-stress model for depression in Generation Scotland

, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Aleix Arnau-Soler (Lead / Corresponding author), Mark J. Adams, Toni-Kim Clarke, Donald J. MacIntyre, Keith Milburn, Lauren Navrady, Caroline Hayward, Andrew McIntosh, Pippa A. Thomson (Lead / Corresponding author)

Research output: Contribution to journalArticle

Abstract

Depression has well-established influences from genetic and environmental risk factors. This has led to the diathesis-stress theory, which assumes a multiplicative gene-by-environment interaction (GxE) effect on risk. Recently, Colodro-Conde et al. empirically tested this theory, using the polygenic risk score for major depressive disorder (PRS, genes) and stressful life events (SLE, environment) effects on depressive symptoms, identifying significant GxE effects with an additive contribution to liability. We have tested the diathesis-stress theory on an independent sample of 4919 individuals. We identified nominally significant positive GxE effects in the full cohort (R2 = 0.08%, p = 0.049) and in women (R2 = 0.19%, p = 0.017), but not in men (R2 = 0.15%, p = 0.07). GxE effects were nominally significant, but only in women, when SLE were split into those in which the respondent plays an active or passive role (R2 = 0.15%, p = 0.038; R2 = 0.16%, p = 0.033, respectively). High PRS increased the risk of depression in participants reporting high numbers of SLE (p = 2.86 × 10-4). However, in those participants who reported no recent SLE, a higher PRS appeared to increase the risk of depressive symptoms in men (β = 0.082, p = 0.016) but had a protective effect in women (β = -0.061, p = 0.037). This difference was nominally significant (p = 0.017). Our study reinforces the evidence of additional risk in the aetiology of depression due to GxE effects. However, larger sample sizes are required to robustly validate these findings.

LanguageEnglish
Article number25
Pages1-10
Number of pages10
JournalTranslational Psychiatry
Volume9
Issue number1
DOIs
Publication statusPublished - 18 Jan 2019

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Disease Susceptibility
Scotland
Depression
Gene-Environment Interaction
Major Depressive Disorder
Sample Size
Genes

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, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Arnau-Soler, A., Adams, M. J., Clarke, T-K., MacIntyre, D. J., ... Thomson, P. A. (2019). A validation of the diathesis-stress model for depression in Generation Scotland. Translational Psychiatry, 9(1), 1-10. [25]. https://doi.org/10.1038/s41398-018-0356-7
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ; Arnau-Soler, Aleix ; Adams, Mark J. ; Clarke, Toni-Kim ; MacIntyre, Donald J. ; Milburn, Keith ; Navrady, Lauren ; Hayward, Caroline ; McIntosh, Andrew ; Thomson, Pippa A. / A validation of the diathesis-stress model for depression in Generation Scotland. In: Translational Psychiatry. 2019 ; Vol. 9, No. 1. pp. 1-10.
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Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Arnau-Soler, A, Adams, MJ, Clarke, T-K, MacIntyre, DJ, Milburn, K, Navrady, L, Hayward, C & McIntosh, A & Thomson, PA 2019, 'A validation of the diathesis-stress model for depression in Generation Scotland', Translational Psychiatry, vol. 9, no. 1, 25, pp. 1-10. https://doi.org/10.1038/s41398-018-0356-7

A validation of the diathesis-stress model for depression in Generation Scotland. /; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Arnau-Soler, Aleix (Lead / Corresponding author); Adams, Mark J.; Clarke, Toni-Kim; MacIntyre, Donald J.; Milburn, Keith; Navrady, Lauren; Hayward, Caroline; McIntosh, Andrew; Thomson, Pippa A. (Lead / Corresponding author).

In: Translational Psychiatry, Vol. 9, No. 1, 25, 18.01.2019, p. 1-10.

Research output: Contribution to journalArticle

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Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Arnau-Soler A, Adams MJ, Clarke T-K, MacIntyre DJ et al. A validation of the diathesis-stress model for depression in Generation Scotland. Translational Psychiatry. 2019 Jan 18;9(1):1-10. 25. https://doi.org/10.1038/s41398-018-0356-7