Role of resilience in modifying the links between genetic propensity for mental disorders and irritability - UTU Research Portal

A1 Refereed original research article in a scientific journal

Role of resilience in modifying the links between genetic propensity for mental disorders and irritability;

Authors: Saarinen, Aino; Lyytikäinen, Leo-Pekka; Lavonius, Veikka; Asikainen, Timo; Sormunen, Elina; Kähönen, Mika; Hietala, Jarmo; Raitakari, Olli; Lehtimäki, Terho; Keltikangas-Järvinen, Liisa

Publisher: Elsevier BV

Publication year: 2026

Journal: Journal of Affective Disorders

Article number: 122174

Volume: 413

ISSN: 0165-0327

eISSN: 1573-2517

DOI: https://doi.org/10.1016/j.jad.2026.122174

Publication's open availability at the time of reporting: Open Access

Publication channel's open availability : Partially Open Access publication channel

Web address : https://doi.org/10.1016/j.jad.2026.122174

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/526965552

Self-archived copy's licence: CC BY

Self-archived copy's version: Publisher`s PDF

Abstract

Aims

We examined (1) whether polygenic risk scores for schizophrenia (PRSSCZ), major depression (PRSMDD), and posttraumatic stress disorder (PRSPTSD) explain irritability between ages 20 and 50 and (2) whether these associations are modified by early psychosocial resilience.

Methods

Participants came from the prospective, population-based Young Finns Study (n = 1272–2212). The most recent available genome-wide association studies were used to calculate PRSs. Irritability was assessed over a 15-year follow-up (participants being 20–50 years old). Early resilience was assessed across five indices: psychological strength, social satisfaction, leisure time activities, responsible health behaviors, and school career. Covariates included early family environment, traumatic experiences, health behaviors, and socioeconomic factors.

Results

PRSMDD and PRSPTSD showed robust positive associations with irritability, whereas PRSSCZ was only modestly associated with higher disposition to behavioral form of irritability and only in earliest adulthood. We did not observe interactions between PRSs and most resilience indices (e.g., psychological strength, social satisfaction). However, school career and leisure time activities had interactions with PRSs, indicating a stronger protective effect against irritability in individuals with higher vs. lower PRSs. PRSMDD and PRSPTSD have clearly more robust associations with irritability compared to PRSSCZ.

Conclusions

Polygenic liabilities for affective disorders but not schizophrenia are associated with higher irritability trajectories between ages 20 and 50 years. Individuals with higher or lower PRSs appeared to benefit from early resilience indices in a largely similar manner, except for school career and leisure time activities, which seemed to have particularly strong protective effects in individuals with high PRSs.

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Funding information in the publication:
This study was financially supported by the Emil Aaltonen Foundation (grant no. 220225), the Finnish Cultural Foundation (grant no. 00250813), and the Research Council of Finland (grant no. 363547). The Young Finns Study has been financially supported by the Research Council of Finland: grants 356405, 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; the Cancer Foundation Finland; Horizon Europe (pBETTER4U_EU, grant number: 101080117); Horizon Europe (CVDLink, grant number 101137278) and the Jane and Aatos Erkko Foundation.