Lotta-Katrin Pries1, Jim van Os1,2,3, Margreet Ten Have4, Ron de Graaf4, Saskia van Dorsselaer4, Maarten Bak1,5, Bochao D Lin6, Kristel R van Eijk7, Gunter Kenis1, Alexander Richards8, Michael C O'Donovan8, Jurjen J Luykx2,6,9, Bart P F Rutten1, Sinan Guloksuz1,10. 1. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands. 2. Department of Psychiatry, UMC (University Medical Center) Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 3. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. 4. Department of Epidemiology, Netherlands Institute of Mental Health and Addiction, Utrecht, the Netherlands. 5. Flexible Assertive Community Treatment, Mondriaan Mental Health, Maastricht, the Netherlands. 6. Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 7. Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands. 8. MRC (Medical Research Council) Center for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom. 9. GGNet Mental Health, Apeldoorn, the Netherlands. 10. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Abstract
Importance: Both adulthood stressful life events (SLEs) and liability for schizophrenia have been associated with poor mental and physical health in the general population, but their interaction remains to be elucidated to improve population-based health outcomes. Objective: To test whether recent SLEs interact with genetic and environmental liability for schizophrenia in models of mental and physical health. Design, Setting, and Participants: The Netherlands Mental Health Survey and Incidence Study-2 is a population-based prospective cohort study designed to investigate the prevalence, incidence, course, and consequences of mental disorders in the Dutch general population. Participants were enrolled from November 5, 2007, to July 31, 2009, and followed up with 3 assessments during 9 years. Follow-up was completed on June 19, 2018, and data were analyzed from September 1 to November 1, 2019. Exposures: Recent SLEs assessed at each wave and aggregate scores of genetic and environmental liability for schizophrenia: polygenic risk score for schizophrenia (PRS-SCZ) trained using the Psychiatric Genomics Consortium analysis results and exposome score for schizophrenia (ES-SCZ) trained using an independent data set. Main Outcomes and Measures: Independent and interacting associations of SLEs with ES-SCZ and PRS-SCZ on mental and physical health assessed at each wave using regression coefficients. Results: Of the 6646 participants included at baseline, the mean (SD) age was 44.26 (12.54) years, and 3672 (55.25%) were female. The SLEs were associated with poorer physical health (B = -3.22 [95% CI, -3.66 to -2.79]) and mental health (B = -3.68 [95% CI, -4.05 to -3.32]). Genetic and environmental liability for schizophrenia was associated with poorer mental health (ES-SCZ: B = -3.07 [95% CI, -3.35 to -2.79]; PRS-SCZ: B = -0.93 [95% CI, -1.31 to -0.54]). Environmental liability was also associated with poorer physical health (B = -3.19 [95% CI, -3.56 to -2.82]). The interaction model showed that ES-SCZ moderated the association of SLEs with mental (B = -1.08 [95% CI, -1.47 to -0.69]) and physical health (B = -0.64 [95% CI, -1.11 to -0.17]), whereas PRS-SCZ did not. Several sensitivity analyses confirmed these results. Conclusions and Relevance: In this study, schizophrenia liability was associated with broad mental health outcomes at the population level. Consistent with the diathesis-stress model, exposure to SLEs, particularly in individuals with high environmental liability for schizophrenia, was associated with poorer health. These findings underline the importance of modifiable environmental factors during the life span for population-based mental health outcomes.
Importance: Both adulthood stressful life events (SLEs) and liability for schizophrenia have been associated with poor mental and physical health in the general population, but their interaction remains to be elucidated to improve population-based health outcomes. Objective: To test whether recent SLEs interact with genetic and environmental liability for schizophrenia in models of mental and physical health. Design, Setting, and Participants: The Netherlands Mental Health Survey and Incidence Study-2 is a population-based prospective cohort study designed to investigate the prevalence, incidence, course, and consequences of mental disorders in the Dutch general population. Participants were enrolled from November 5, 2007, to July 31, 2009, and followed up with 3 assessments during 9 years. Follow-up was completed on June 19, 2018, and data were analyzed from September 1 to November 1, 2019. Exposures: Recent SLEs assessed at each wave and aggregate scores of genetic and environmental liability for schizophrenia: polygenic risk score for schizophrenia (PRS-SCZ) trained using the Psychiatric Genomics Consortium analysis results and exposome score for schizophrenia (ES-SCZ) trained using an independent data set. Main Outcomes and Measures: Independent and interacting associations of SLEs with ES-SCZ and PRS-SCZ on mental and physical health assessed at each wave using regression coefficients. Results: Of the 6646 participants included at baseline, the mean (SD) age was 44.26 (12.54) years, and 3672 (55.25%) were female. The SLEs were associated with poorer physical health (B = -3.22 [95% CI, -3.66 to -2.79]) and mental health (B = -3.68 [95% CI, -4.05 to -3.32]). Genetic and environmental liability for schizophrenia was associated with poorer mental health (ES-SCZ: B = -3.07 [95% CI, -3.35 to -2.79]; PRS-SCZ: B = -0.93 [95% CI, -1.31 to -0.54]). Environmental liability was also associated with poorer physical health (B = -3.19 [95% CI, -3.56 to -2.82]). The interaction model showed that ES-SCZ moderated the association of SLEs with mental (B = -1.08 [95% CI, -1.47 to -0.69]) and physical health (B = -0.64 [95% CI, -1.11 to -0.17]), whereas PRS-SCZ did not. Several sensitivity analyses confirmed these results. Conclusions and Relevance: In this study, schizophrenia liability was associated with broad mental health outcomes at the population level. Consistent with the diathesis-stress model, exposure to SLEs, particularly in individuals with high environmental liability for schizophrenia, was associated with poorer health. These findings underline the importance of modifiable environmental factors during the life span for population-based mental health outcomes.
Authors: L Belbasis; C A Köhler; N Stefanis; B Stubbs; J van Os; E Vieta; M V Seeman; C Arango; A F Carvalho; E Evangelou Journal: Acta Psychiatr Scand Date: 2017-12-30 Impact factor: 6.392
Authors: Jim van Os; Lotta-Katrin Pries; Philippe Delespaul; Gunter Kenis; Jurjen J Luykx; Bochao D Lin; Alexander L Richards; Berna Akdede; Tolga Binbay; Vesile Altınyazar; Berna Yalınçetin; Güvem Gümüş-Akay; Burçin Cihan; Haldun Soygür; Halis Ulaş; Eylem Şahin Cankurtaran; Semra Ulusoy Kaymak; Marina M Mihaljevic; Sanja Andric Petrovic; Tijana Mirjanic; Miguel Bernardo; Bibiana Cabrera; Julio Bobes; Pilar A Saiz; María Paz García-Portilla; Julio Sanjuan; Eduardo J Aguilar; José Luis Santos; Estela Jiménez-López; Manuel Arrojo; Angel Carracedo; Gonzalo López; Javier González-Peñas; Mara Parellada; Nadja P Maric; Cem Atbaşoğlu; Alp Ucok; Köksal Alptekin; Meram Can Saka; Celso Arango; Michael O'Donovan; Bart P F Rutten; Sinan Guloksuz Journal: Psychol Med Date: 2019-08-15 Impact factor: 7.723
Authors: Stanley Zammit; Marian Hamshere; Sarah Dwyer; Lyudmila Georgiva; Nic Timpson; Valentina Moskvina; Alexander Richards; David M Evans; Glyn Lewis; Peter Jones; Michael J Owen; Michael C O'Donovan Journal: Schizophr Bull Date: 2013-10-30 Impact factor: 9.306
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