Stress related disorders and subsequent risk of life threatening infections: population based sibling controlled cohort study

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.

Fig 1

Study design. *Sepsis, endocarditis, and meningitis or other central nervous system infections. †Randomly selected from general population: individuals without a diagnosis of stress related disorder or major life threatening infection at diagnosis date of the index individual

Fig 2

Crude incidence and hazard ratios (95% confidence intervals) for life threatening infections among individuals with any stress related disorder and post-traumatic stress disorder (exposed) compared with full siblings or matched individuals without such a diagnosis (unexposed). *Cox models were stratified by family identifiers and adjusted for sex, birth year, education level, family income, marital status, and history of severe somatic diseases, other psychiatric disorder, and inpatient visit for infectious diseases. †Cox models were stratified by matching identifiers (sex, birth year, and county of birth) and adjusted for education level; family income; marital status; history of severe somatic diseases, other psychiatric disorder, and inpatient visit for infectious diseases; and family history of major life threatening infections. CNS=central nervous system

Fig 3

Association between stress related disorders and life threatening infections by age at index date. *Restricted cubic splines were applied on age at index date, with five knots placed at 5, 27.5, 50, 72.5, and 95 quantiles of the distribution of outcome events. Age varying hazard ratios were then predicted based on fully adjusted Cox models where interaction terms between stress related disorders and splined age profiles were added. In sibling based analysis, the cox models were stratified by family identifiers and adjusted for sex, birth year, education level, family income, marital status, and history of severe somatic diseases, inpatient visit for infectious diseases, and other psychiatric disorder. In population based analysis, the cox models were stratified by matching identifiers—that is, sex, birth year, and county of birth, and adjusted for education level; family income; marital status; history of severe somatic diseases, inpatient visit for infectious diseases, and other psychiatric disorders; and family history of major life threatening infections. Shaded area represents 95% confidence intervals