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Sepsis and Subsequent Psychiatric Morbidity : A Nationwide Population-Based Matched Cohort Study, 2008–2019

Wetterberg, Hanna LU orcid ; Nilsson, Anton LU ; Linder, Adam LU ; Lengquist, Maria LU orcid ; Frigyesi, Attila LU ; Sundén-Cullberg, Jonas and Inghammar, Malin LU (2026) In Critical Care Medicine
Abstract

Objectives: – To quantify the risk of incident psychiatric morbidity after community-acquired sepsis and assess whether new chronic diseases mediate the association. Design: – Nationwide, population-based matched register cohort; hazards estimated with weighted Cox regression. Setting: – Sweden, linking the National Quality Sepsis Registry, National Patient Register, Prescribed Drug Register, and population registers. Patients: – Ten thousand three hundred eight adults (≥ 18 yr) treated in an ICU for sepsis (2008–2019), matched to 155, 705 population controls by sex, age, region, and year. Individuals with a psychiatric diagnosis within 5 years or psychotropic medication within 1 year before index were excluded. Interventions: – None.... (More)

Objectives: – To quantify the risk of incident psychiatric morbidity after community-acquired sepsis and assess whether new chronic diseases mediate the association. Design: – Nationwide, population-based matched register cohort; hazards estimated with weighted Cox regression. Setting: – Sweden, linking the National Quality Sepsis Registry, National Patient Register, Prescribed Drug Register, and population registers. Patients: – Ten thousand three hundred eight adults (≥ 18 yr) treated in an ICU for sepsis (2008–2019), matched to 155, 705 population controls by sex, age, region, and year. Individuals with a psychiatric diagnosis within 5 years or psychotropic medication within 1 year before index were excluded. Interventions: – None. Measurements and Main Results: – The primary outcome, psychiatric event, was first occurrence after index date of either initiation of a psychotropic medication (anatomic therapeutic chemical classification system code N05A, N05BA, N05C, N06A) in the Prescribed Drug Register (capturing prescriptions from primary and specialist care) or a new International Classification of Diseases, 10th Edition mood (F3) or anxiety (F4) diagnosis in specialist care. Weighted Cox models balanced baseline covariates. We used a Landmark approach with risk sets at 0–30, 31–90, 91–365 days; 1–3, 3–5, and greater than or equal to 5 years after the index date. Sepsis was associated with increased hazards of psychiatric events vs. matched controls, with the strongest associations in the first year (0–30 d: adjusted hazard ratio [aHR], 6.2 [5.0–7.7]; 31–90 d: aHR, 7.4 [6.5–8.6]; and 91–365 d: aHR, 2.3 [2.1–2.5]) attenuating over time but remaining elevated through 5 years (1–3 yr: aHR, 1.2 [1.1–1.5]; 3–5 yr: aHR, 1.3 [1.1–1.5]; and ≥ 5 yr: aHR, 1.1 [0.9–1.3]). In mediation analyses considering incident chronic diseases, estimates changed little, suggesting that these conditions did not mediate the association. Conclusions: – Patients with sepsis had a higher subsequent incidence of psychiatric events compared with matched population controls, with a persistently elevated risk for at least 5 years. This increased risk suggests that sepsis may have a long-term impact on psychiatric health, warranting consideration of preventive strategies.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
mediation analysis, mental disorders, population control, prescriptions, sepsis
in
Critical Care Medicine
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:105035480842
  • pmid:41870200
ISSN
0090-3493
DOI
10.1097/CCM.0000000000007105
language
English
LU publication?
yes
id
87e12a8c-3028-4dc6-969c-a66c05b88e69
date added to LUP
2026-05-25 14:51:03
date last changed
2026-05-25 14:51:49
@article{87e12a8c-3028-4dc6-969c-a66c05b88e69,
  abstract     = {{<p>Objectives: – To quantify the risk of incident psychiatric morbidity after community-acquired sepsis and assess whether new chronic diseases mediate the association. Design: – Nationwide, population-based matched register cohort; hazards estimated with weighted Cox regression. Setting: – Sweden, linking the National Quality Sepsis Registry, National Patient Register, Prescribed Drug Register, and population registers. Patients: – Ten thousand three hundred eight adults (≥ 18 yr) treated in an ICU for sepsis (2008–2019), matched to 155, 705 population controls by sex, age, region, and year. Individuals with a psychiatric diagnosis within 5 years or psychotropic medication within 1 year before index were excluded. Interventions: – None. Measurements and Main Results: – The primary outcome, psychiatric event, was first occurrence after index date of either initiation of a psychotropic medication (anatomic therapeutic chemical classification system code N05A, N05BA, N05C, N06A) in the Prescribed Drug Register (capturing prescriptions from primary and specialist care) or a new International Classification of Diseases, 10th Edition mood (F3) or anxiety (F4) diagnosis in specialist care. Weighted Cox models balanced baseline covariates. We used a Landmark approach with risk sets at 0–30, 31–90, 91–365 days; 1–3, 3–5, and greater than or equal to 5 years after the index date. Sepsis was associated with increased hazards of psychiatric events vs. matched controls, with the strongest associations in the first year (0–30 d: adjusted hazard ratio [aHR], 6.2 [5.0–7.7]; 31–90 d: aHR, 7.4 [6.5–8.6]; and 91–365 d: aHR, 2.3 [2.1–2.5]) attenuating over time but remaining elevated through 5 years (1–3 yr: aHR, 1.2 [1.1–1.5]; 3–5 yr: aHR, 1.3 [1.1–1.5]; and ≥ 5 yr: aHR, 1.1 [0.9–1.3]). In mediation analyses considering incident chronic diseases, estimates changed little, suggesting that these conditions did not mediate the association. Conclusions: – Patients with sepsis had a higher subsequent incidence of psychiatric events compared with matched population controls, with a persistently elevated risk for at least 5 years. This increased risk suggests that sepsis may have a long-term impact on psychiatric health, warranting consideration of preventive strategies.</p>}},
  author       = {{Wetterberg, Hanna and Nilsson, Anton and Linder, Adam and Lengquist, Maria and Frigyesi, Attila and Sundén-Cullberg, Jonas and Inghammar, Malin}},
  issn         = {{0090-3493}},
  keywords     = {{mediation analysis; mental disorders; population control; prescriptions; sepsis}},
  language     = {{eng}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Critical Care Medicine}},
  title        = {{Sepsis and Subsequent Psychiatric Morbidity : A Nationwide Population-Based Matched Cohort Study, 2008–2019}},
  url          = {{http://dx.doi.org/10.1097/CCM.0000000000007105}},
  doi          = {{10.1097/CCM.0000000000007105}},
  year         = {{2026}},
}