A Validation of the Diathesis-stress Model for Depression in Generation Scotland

Overview

Journal Transl Psychiatry

Specialties Psychiatry
Public Health

Date 2019 Jan 20

PMID 30659167

Citations 24

Authors

Aleix Arnau-Soler

Mark J Adams

Toni-Kim Clarke

Donald J MacIntyre

Keith Milburn

Lauren Navrady

Caroline Hayward

Andrew McIntosh

Pippa A Thomson

Affiliations

Soon will be listed here.

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 (R = 0.08%, p = 0.049) and in women (R = 0.19%, p = 0.017), but not in men (R = 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 (R = 0.15%, p = 0.038; R = 0.16%, p = 0.033, respectively). High PRS increased the risk of depression in participants reporting high numbers of SLE (p = 2.86 × 10). 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.

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References

Iyegbe C, Campbell D, Butler A, Ajnakina O, Sham P . The emerging molecular architecture of schizophrenia, polygenic risk scores and the clinical implications for GxE research. Soc Psychiatry Psychiatr Epidemiol. 2014; 49(2):169-82. DOI: 10.1007/s00127-014-0823-2. View

Kerr S, Campbell A, Murphy L, Hayward C, Jackson C, Wain L . Pedigree and genotyping quality analyses of over 10,000 DNA samples from the Generation Scotland: Scottish Family Health Study. BMC Med Genet. 2013; 14:38. PMC: 3614907. DOI: 10.1186/1471-2350-14-38. View

Smith B, Campbell H, Blackwood D, Connell J, Connor M, Deary I . Generation Scotland: the Scottish Family Health Study; a new resource for researching genes and heritability. BMC Med Genet. 2006; 7:74. PMC: 1592477. DOI: 10.1186/1471-2350-7-74. View

Kendler K, Karkowski L, Prescott C . Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry. 1999; 156(6):837-41. DOI: 10.1176/ajp.156.6.837. View

ORourke S, MacHale S, Signorini D, Dennis M . Detecting psychiatric morbidity after stroke: comparison of the GHQ and the HAD Scale. Stroke. 1998; 29(5):980-5. DOI: 10.1161/01.str.29.5.980. View

Piccinelli M, Wilkinson G . Gender differences in depression. Critical review. Br J Psychiatry. 2000; 177:486-92. DOI: 10.1192/bjp.177.6.486. View

Paykel E . Life events and affective disorders. Acta Psychiatr Scand Suppl. 2003; (418):61-6. DOI: 10.1034/j.1600-0447.108.s418.13.x. View

Wray N, Lee S, Mehta D, Vinkhuyzen A, Dudbridge F, Middeldorp C . Research review: Polygenic methods and their application to psychiatric traits. J Child Psychol Psychiatry. 2014; 55(10):1068-87. DOI: 10.1111/jcpp.12295. View

Belsky J, Beaver K . Cumulative-genetic plasticity, parenting and adolescent self-regulation. J Child Psychol Psychiatry. 2010; 52(5):619-26. PMC: 4357655. DOI: 10.1111/j.1469-7610.2010.02327.x. View

10.

Motrico E, Moreno-Kustner B, Luna J, Torres-Gonzalez F, King M, Nazareth I . Psychometric properties of the List of Threatening Experiences--LTE and its association with psychosocial factors and mental disorders according to different scoring methods. J Affect Disord. 2013; 150(3):931-40. DOI: 10.1016/j.jad.2013.05.017. View

11.

Euesden J, Lewis C, OReilly P . PRSice: Polygenic Risk Score software. Bioinformatics. 2015; 31(9):1466-8. PMC: 4410663. DOI: 10.1093/bioinformatics/btu848. View

12.

Otowa T, Kawamura Y, Tsutsumi A, Kawakami N, Kan C, Shimada T . The First Pilot Genome-Wide Gene-Environment Study of Depression in the Japanese Population. PLoS One. 2016; 11(8):e0160823. PMC: 4986946. DOI: 10.1371/journal.pone.0160823. View

13.

Smith B, Campbell A, Linksted P, Fitzpatrick B, Jackson C, Kerr S . Cohort Profile: Generation Scotland: Scottish Family Health Study (GS:SFHS). The study, its participants and their potential for genetic research on health and illness. Int J Epidemiol. 2012; 42(3):689-700. DOI: 10.1093/ije/dys084. View

14.

Musliner K, Seifuddin F, Judy J, Pirooznia M, Goes F, Zandi P . Polygenic risk, stressful life events and depressive symptoms in older adults: a polygenic score analysis. Psychol Med. 2014; 45(8):1709-20. PMC: 4412793. DOI: 10.1017/S0033291714002839. View

15.

Banks M . Validation of the General Health Questionnaire in a young community sample. Psychol Med. 1983; 13(2):349-53. DOI: 10.1017/s0033291700050972. View

16.

Van de Velde S, Bracke P, Levecque K . Gender differences in depression in 23 European countries. Cross-national variation in the gender gap in depression. Soc Sci Med. 2010; 71(2):305-313. DOI: 10.1016/j.socscimed.2010.03.035. View

17.

Polderman T, Benyamin B, de Leeuw C, Sullivan P, van Bochoven A, Visscher P . Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet. 2015; 47(7):702-9. DOI: 10.1038/ng.3285. View

18.

Nagy R, Boutin T, Marten J, Huffman J, Kerr S, Campbell A . Exploration of haplotype research consortium imputation for genome-wide association studies in 20,032 Generation Scotland participants. Genome Med. 2017; 9(1):23. PMC: 5339960. DOI: 10.1186/s13073-017-0414-4. View

19.

Wray N, Ripke S, Mattheisen M, Trzaskowski M, Byrne E, Abdellaoui A . Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet. 2018; 50(5):668-681. PMC: 5934326. DOI: 10.1038/s41588-018-0090-3. View

20.

Labonte B, Engmann O, Purushothaman I, Menard C, Wang J, Tan C . Corrigendum: Sex-specific transcriptional signatures in human depression. Nat Med. 2018; 24(4):525. DOI: 10.1038/nm0418-525d. View