A population-based multigenerational family co-aggregation study of severe infections and obsessive-compulsive disorder.

OCDTWIN study Obsessive-compulsive disorder PANDAS PANS co-aggregation study cohort study severe infections

Journal

Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264

Informations de publication

Date de publication:
14 Sep 2024
Historique:
received: 11 07 2024
revised: 06 09 2024
accepted: 08 09 2024
medline: 17 9 2024
pubmed: 17 9 2024
entrez: 16 9 2024
Statut: aheadofprint

Résumé

Postinfectious autoimmune processes have been proposed as potential causal factors for obsessive-compulsive disorder (OCD). This large population-based study aimed to clarify the co-aggregation pattern between severe infections and OCD across clusters of relatives with varying degrees of relatedness. We identified 4,916,898 individuals born in Sweden between 1960 and 2008 and followed them until 2020. Each individual was linked to their first- and second-degree relatives, including monozygotic (MZ) and dizygotic (DZ) twins, mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles, and cousins. OCD and infection diagnoses from inpatient and specialized outpatient units 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 (HRs). Dose-response associations were examined using logistic regression models. Relatives of probands with severe infections exhibited a higher risk of OCD, increasing with genetic relatedness, with HRs (95% CI) ranging from 1.46 (1.07-1.98) in MZ 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. The results strongly suggest that the association between severe infections and OCD may be largely driven by shared genetic factors.

Sections du résumé

BACKGROUND BACKGROUND
Postinfectious autoimmune processes have been proposed as potential causal factors for obsessive-compulsive disorder (OCD). This large population-based study aimed to clarify the co-aggregation pattern between severe infections and OCD across clusters of relatives with varying degrees of relatedness.
METHODS METHODS
We identified 4,916,898 individuals born in Sweden between 1960 and 2008 and followed them until 2020. Each individual was linked to their first- and second-degree relatives, including monozygotic (MZ) and dizygotic (DZ) twins, mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles, and cousins. OCD and infection diagnoses from inpatient and specialized outpatient units 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 (HRs). Dose-response associations were examined using logistic regression models.
RESULTS RESULTS
Relatives of probands with severe infections exhibited a higher risk of OCD, increasing with genetic relatedness, with HRs (95% CI) ranging from 1.46 (1.07-1.98) in MZ 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 CONCLUSIONS
The results strongly suggest that the association between severe infections and OCD may be largely driven by shared genetic factors.

Identifiants

pubmed: 39284402
pii: S0006-3223(24)01587-7
doi: 10.1016/j.biopsych.2024.09.004
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Josep Pol-Fuster (J)

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden. Electronic address: josep.pol.fuster@ki.se.

Lorena Fernández de la Cruz (L)

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.

Jan Beucke (J)

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Institute for Systems Medicine, Department of Human Medicine, MSH Medical School Hamburg, Hamburg, Germany.

Eva Hesselmark (E)

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.

James J Crowley (JJ)

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Department of Genetics, University of North Carolina at, Chapel Hill, NC, USA.

Elles de Schipper (E)

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.

Isabell Brikell (I)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Zheng Chang (Z)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Brian M D'Onofrio (BM)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.

Henrik Larsson (H)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.

Paul Lichtenstein (P)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Ralf Kuja-Halkola (R)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

David Mataix-Cols (D)

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden.

Classifications MeSH