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.

Stress related disorders and physical health

“…Key among them is a disturbed hypothalamic-pituitary-adrenal axis, with reduced cortisol levels or receptor resistance leading to heightened adrenergic tone and excessive inflammation 5. Song and colleagues argue that their results are consistent with this hypothesis and the resultant overproduction of inflammatory cytokines 3…”

“…Song and colleagues’ methodology is strong but they correctly acknowledge some limitations and an inability to determine causality 3. As with many cohort studies of PTSD, not controlling for exposure to trauma and lack of standardised assessment of the PTSD phenotype give further cause for caution when interpreting the results.…”

“…Less well recognised is the substantial physical comorbidity associated with these conditions, highlighting an ongoing tendency to a dualistic view of mind and body 2. Song and colleagues’ (doi:10.1136/bmj.l5784) concerning finding that people with stress related disorders are at significantly heightened risk of life threatening infections3 challenges this notion and adds to previous research suggesting overlapping mechanistic pathways between mental and physical health 4…”

The Psychology of the Common Cold and Influenza: Implications for COVID-19

“…Many of the results from experimentally-induced URTI studies have been replicated in research on naturally-occurring illnesses [8,9]. In addition, a series of studies (the Pittsburgh studies) continued to examine experimentally-induced colds (for a review, see [10], a list of studies is given in table 1]).…”

Immunomodulation: new avenues for treatment

“…Song et al’s thought provoking paper and the accompanying editorial by Bisson highlight the life limiting sequelae of chronic hypothalamic pituitary adrenal (HPA) axis dysregulation secondary to post-traumatic stress disorder (PTSD) 12. While these chronic inflammatory effects of PTSD are also associated with huge cardiac morbidity and mortality,3 and an increase in autoimmune disease and somatisation,4 these findings also represent new avenues for treatment.…”