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A Population-Based Multigenerational Family Coaggregation Study of Severe Infections and Obsessive-Compulsive Disorder

Pol-Fuster, Josep ; Fernández de la Cruz, Lorena ; Beucke, Jan C. ; Hesselmark, Eva ; Crowley, James J. ; de Schipper, Elles ; Brikell, Isabell ; Chang, Zheng ; D'Onofrio, Brian M. and Larsson, Henrik , et al. (2024) In Biological Psychiatry
Abstract

Background: Postinfectious autoimmune processes have been proposed as potential causal risk factors for obsessive-compulsive disorder (OCD). In this large population-based study, we aimed to clarify the familial coaggregation pattern between severe infections and OCD across clusters of relatives with varying degrees of relatedness. Methods: We identified 4,916,898 individuals born in Sweden between 1960 and 2008 and followed them until the end of 2020. Each individual was linked to their first-, second-, and third-degree relatives, including monozygotic and dizygotic twins, mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles, and cousins. OCD and infection diagnoses from inpatient and specialized... (More)

Background: Postinfectious autoimmune processes have been proposed as potential causal risk factors for obsessive-compulsive disorder (OCD). In this large population-based study, we aimed to clarify the familial coaggregation pattern between severe infections and OCD across clusters of relatives with varying degrees of relatedness. Methods: We identified 4,916,898 individuals born in Sweden between 1960 and 2008 and followed them until the end of 2020. Each individual was linked to their first-, second-, and third-degree relatives, including monozygotic and dizygotic twins, mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles, and cousins. OCD and infection diagnoses from inpatient and specialized outpatient settings were retrieved from the Swedish National Patient Register. We compared the risk of OCD in relatives of probands with severe infections to those of probands without severe infections. Cox proportional hazard regression models, incorporating time-varying exposures, were used to estimate hazard ratios. Dose-response associations were examined using logistic regression models. Results: Relatives of probands with severe infections had a higher risk of OCD, which increased with genetic relatedness, with hazard ratios (95% CI) ranging from 1.46 (1.07–1.98) in monozygotic twins to 1.10 (1.09–1.11) in cousins. The results remained robust after adjusting for severe infections among relatives, OCD in probands, and comorbid autoimmune disorders in both probands and relatives. A dose-response association was observed between the number of infections in the probands and their odds of OCD, as well as in their relatives. Conclusions: The results strongly suggest that the association between severe infections and OCD may be largely driven by shared genetic factors.

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Contribution to journal
publication status
epub
subject
keywords
Familial coaggregation study, Infections, Obsessive-compulsive disorder, OCDTWIN study, PANDAS, PANS
in
Biological Psychiatry
publisher
Elsevier
external identifiers
  • pmid:39284402
  • scopus:85208684690
ISSN
0006-3223
DOI
10.1016/j.biopsych.2024.09.004
language
English
LU publication?
yes
id
4bc9f073-aea0-4dbc-a998-e8dd7f3aae28
date added to LUP
2025-02-17 15:45:05
date last changed
2025-07-08 03:26:53
@article{4bc9f073-aea0-4dbc-a998-e8dd7f3aae28,
  abstract     = {{<p>Background: Postinfectious autoimmune processes have been proposed as potential causal risk factors for obsessive-compulsive disorder (OCD). In this large population-based study, we aimed to clarify the familial coaggregation pattern between severe infections and OCD across clusters of relatives with varying degrees of relatedness. Methods: We identified 4,916,898 individuals born in Sweden between 1960 and 2008 and followed them until the end of 2020. Each individual was linked to their first-, second-, and third-degree relatives, including monozygotic and dizygotic twins, mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles, and cousins. OCD and infection diagnoses from inpatient and specialized outpatient settings were retrieved from the Swedish National Patient Register. We compared the risk of OCD in relatives of probands with severe infections to those of probands without severe infections. Cox proportional hazard regression models, incorporating time-varying exposures, were used to estimate hazard ratios. Dose-response associations were examined using logistic regression models. Results: Relatives of probands with severe infections had a higher risk of OCD, which increased with genetic relatedness, with hazard ratios (95% CI) ranging from 1.46 (1.07–1.98) in monozygotic twins to 1.10 (1.09–1.11) in cousins. The results remained robust after adjusting for severe infections among relatives, OCD in probands, and comorbid autoimmune disorders in both probands and relatives. A dose-response association was observed between the number of infections in the probands and their odds of OCD, as well as in their relatives. Conclusions: The results strongly suggest that the association between severe infections and OCD may be largely driven by shared genetic factors.</p>}},
  author       = {{Pol-Fuster, Josep and Fernández de la Cruz, Lorena and Beucke, Jan C. and Hesselmark, Eva and Crowley, James J. and de Schipper, Elles and Brikell, Isabell and Chang, Zheng and D'Onofrio, Brian M. and Larsson, Henrik and Lichtenstein, Paul and Kuja-Halkola, Ralf and Mataix-Cols, David}},
  issn         = {{0006-3223}},
  keywords     = {{Familial coaggregation study; Infections; Obsessive-compulsive disorder; OCDTWIN study; PANDAS; PANS}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Biological Psychiatry}},
  title        = {{A Population-Based Multigenerational Family Coaggregation Study of Severe Infections and Obsessive-Compulsive Disorder}},
  url          = {{http://dx.doi.org/10.1016/j.biopsych.2024.09.004}},
  doi          = {{10.1016/j.biopsych.2024.09.004}},
  year         = {{2024}},
}