Stress related disorders and subsequent risk of life threatening infections: population based sibling controlled cohort studyBMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l5784 (Published 23 October 2019) Cite this as: BMJ 2019;367:l5784
- Huan Song, postdoctoral fellow123,
- Katja Fall, associate professor24,
- Fang Fang, associate professor2,
- Helga Erlendsdóttir, biomedical scientist56,
- Donghao Lu, postdoctoral fellow2,
- David Mataix-Cols, professor78,
- Lorena Fernández de la Cruz, assistant professor78,
- Brian M. D’Onofrio, professor29,
- Paul Lichtenstein, professor2,
- Magnús Gottfreðsson, professor510,
- Catarina Almqvist, professor211,
- Unnur A Valdimarsdóttir, professor1212
- 1Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Sturlugata 8, 101 Reykjavík, Iceland
- 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- 3West China Biomedical Big Data Centre, West China Hospital, Sichuan University, Chengdu, China
- 4Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden
- 5Faculty of Medicine, University of Iceland, Reykjavík, Iceland
- 6Department of Clinical Microbiology, Landspítali University Hospital, Reykjavík, Iceland
- 7Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden
- 8Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
- 9Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA
- 10Department of Infectious Diseases, Landspítali University Hospital, Reykjavik, Iceland
- 11Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
- 12Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA
- Correspondence to: H Song @CPHIceland on Twitter) (or
- Accepted 10 September 2019
Objective To assess whether severe psychiatric reactions to trauma and other adversities are associated with subsequent risk of life threatening infections.
Design Population and sibling matched cohort study.
Setting Swedish population.
Participants 144 919 individuals with stress related disorders (post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) identified from 1987 to 2013 compared with 184 612 full siblings of individuals with a diagnosed stress related disorder and 1 449 190 matched individuals without such a diagnosis from the general population.
Main outcome measures A first inpatient or outpatient visit with a primary diagnosis of severe infections with high mortality rates (ie, sepsis, endocarditis, and meningitis or other central nervous system infections) from the Swedish National Patient Register, and deaths from these infections or infections of any origin from the Cause of Death Register. After controlling for multiple confounders, Cox models were used to estimate hazard ratios of these life threatening infections.
Results The average age at diagnosis of a stress related disorder was 37 years (55 541, 38.3% men). During a mean follow-up of eight years, the incidence of life threatening infections per 1000 person years was 2.9 in individuals with a stress related disorder, 1.7 in siblings without a diagnosis, and 1.3 in matched individuals without a diagnosis. Compared with full siblings without a diagnosis of a stress related disorder, individuals with such a diagnosis were at increased risk of life threatening infections (hazard ratio for any stress related disorder was 1.47 (95% confidence intervals1.37 to 1.58) and for PTSD was 1.92 (1.46 to 2.52)). Corresponding estimates in the population based analysis were similar (1.58 (1.51 to 1.65) for any stress related disorder, P=0.09 for difference between sibling and population based comparison, and 1.95 (1.66 to 2.28) for PTSD, P=0.92 for difference). Stress related disorders were associated with all studied life threatening infections, with the highest relative risk observed for meningitis (sibling based analysis 1.63 (1.23 to 2.16)) and endocarditis (1.57 (1.08 to 2.30)). Younger age at diagnosis of a stress related disorder and the presence of psychiatric comorbidity, especially substance use disorders, were associated with higher hazard ratios, whereas use of selective serotonin reuptake inhibitors in the first year after diagnosis of a stress related disorder was associated with attenuated hazard ratios.
Conclusion In the Swedish population, stress related disorders were associated with a subsequent risk of life threatening infections, after controlling for familial background and physical or psychiatric comorbidities.
Contributors: HS and UAV conceived and designed the study. HS, UAV, KF, and FF analysed the data. UAV, HS, KF, FF, HE, DL, DM-C, LFC, BMD’O, PL, MG, and CA interpreted the data. HS, UAV, KF, FF, HE, DL, DM-C, LFC, BMD’O, PL, MG, and CA drafted the manuscript: HS and UAV had full access to all the data in the study and take responsibility for the integrity and accuracy of the data. HS and UAV are the guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Funding: The study was supported by Grant of Excellence, Icelandic Research Fund (grant No 163362-051, UAV), and European Research Council (ERC) consolidator grant (StressGene, grant No 726413, UAV); the Karolinska Institutet (Senior Researcher Award and Strategic Research Area in Epidemiology, FF); the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework (grant No 340-2013-5867, CA); and the West China Hospital, Sichuan University (1.3.5 Project for Disciplines of Excellence, grant No ZYJC18010, HS). This funding source had no role in study design, data collection, data analysis, data interpretation, writing of the scientific article, or the decision to submit the paper for publication.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: the study was supported by Grant of Excellence, Icelandic Research Fund (grant No 163362-051, UAV), and European Research Council (ERC) consolidator grant (StressGene, grant No 726413, UAV); the Karolinska Institutet (Senior Researcher Award and Strategic Research Area in Epidemiology, FF); the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework (grant No 340-2013-5867, CA); and the West China Hospital, Sichuan University (1.3.5 Project for Disciplines of Excellence, grant No ZYJC18010, HS); no financial relationships with any organisation that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This study was approved by the regional ethics review board in Stockholm, Sweden (Dnr 2013/862-31/5).
Data sharing: No additional data available.
The study guarantors (HS and UAV) affirm that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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