Stress related disorders and subsequent risk of life threatening infections: population based sibling controlled cohort study [压力相关疾病与生命威胁感染的后续风险：基于人群的兄弟姐妹对照研究]

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BMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l5784 (Published 23 October 2019)
Cite this as: BMJ 2019;367:l5784

Authors
Huan Song, Katja Fall, Fang Fang, Helga Erlendsdóttir, Donghao Lu, David Mataix-Cols, Lorena Fernández de la Cruz, Brian M. D’Onofrio, Paul Lichtenstein, Magnús Gottfreðsson, Catarina Almqvist, Unnur A Valdimarsdóttir

Abstract
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.