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

Josep Pol-Fuster; Lorena Fernández de la Cruz; Jan C. Beucke; Eva Hesselmark; James J. Crowley; Elles de Schipper; Isabell Brikell; Zheng Chang; Brian M. D'Onofrio; Henrik Larsson; Paul Lichtenstein; Ralf Kuja-Halkola; David Mataix-Cols

doi:10.1016/j.biopsych.2024.09.004

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

Josep Pol-Fuster^*, Lorena Fernández de la Cruz, Jan C. Beucke, Eva Hesselmark, James J. Crowley, Elles de Schipper, Isabell Brikell, Zheng Chang, Brian M. D'Onofrio, Henrik Larsson, Paul Lichtenstein, Ralf Kuja-Halkola, David Mataix-Cols

^*Corresponding author for this work

Department of Biomedicine - Forskning og uddannelse, Skou-bygningen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

1 Citation (Scopus)

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 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.

Original language	English
Journal	Biological Psychiatry
Volume	97
Issue	7
Pages (from-to)	672-677
Number of pages	6
ISSN	0006-3223
DOIs	https://doi.org/10.1016/j.biopsych.2024.09.004
Publication status	Published - 1 Apr 2025

Keywords

Familial coaggregation study
Infections
Obsessive-compulsive disorder
OCDTWIN study
PANDAS
PANS

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Pol-Fuster, J., Fernández de la Cruz, L., Beucke, J. C., Hesselmark, E., Crowley, J. J., de Schipper, E., Brikell, I., Chang, Z., D'Onofrio, B. M., Larsson, H., Lichtenstein, P., Kuja-Halkola, R., & Mataix-Cols, D. (2025). A Population-Based Multigenerational Family Coaggregation Study of Severe Infections and Obsessive-Compulsive Disorder. Biological Psychiatry, 97(7), 672-677. https://doi.org/10.1016/j.biopsych.2024.09.004

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title = "A Population-Based Multigenerational Family Coaggregation Study of Severe Infections and Obsessive-Compulsive Disorder",

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 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.",

keywords = "Familial coaggregation study, Infections, Obsessive-compulsive disorder, OCDTWIN study, PANDAS, PANS",

author = "Josep Pol-Fuster and {Fern{\'a}ndez de la Cruz}, Lorena and Beucke, {Jan C.} and Eva Hesselmark and Crowley, {James J.} and {de Schipper}, Elles and Isabell Brikell and Zheng Chang and D'Onofrio, {Brian M.} and Henrik Larsson and Paul Lichtenstein and Ralf Kuja-Halkola and David Mataix-Cols",

year = "2025",

month = apr,

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doi = "10.1016/j.biopsych.2024.09.004",

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Pol-Fuster, J, Fernández de la Cruz, L, Beucke, JC, Hesselmark, E, Crowley, JJ, de Schipper, E, Brikell, I, Chang, Z, D'Onofrio, BM, Larsson, H, Lichtenstein, P, Kuja-Halkola, R & Mataix-Cols, D 2025, 'A Population-Based Multigenerational Family Coaggregation Study of Severe Infections and Obsessive-Compulsive Disorder', Biological Psychiatry, vol. 97, no. 7, pp. 672-677. https://doi.org/10.1016/j.biopsych.2024.09.004

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. et al.
In: Biological Psychiatry, Vol. 97, No. 7, 01.04.2025, p. 672-677.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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T1 - A Population-Based Multigenerational Family Coaggregation Study of Severe Infections and Obsessive-Compulsive Disorder

AU - Pol-Fuster, Josep

AU - Fernández de la Cruz, Lorena

AU - Beucke, Jan C.

AU - Hesselmark, Eva

AU - Crowley, James J.

AU - de Schipper, Elles

AU - Brikell, Isabell

AU - Chang, Zheng

AU - D'Onofrio, Brian M.

AU - Larsson, Henrik

AU - Lichtenstein, Paul

AU - Kuja-Halkola, Ralf

AU - Mataix-Cols, David

PY - 2025/4/1

Y1 - 2025/4/1

N2 - 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.

AB - 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.

KW - Familial coaggregation study

KW - Infections

KW - Obsessive-compulsive disorder

KW - OCDTWIN study

KW - PANDAS

KW - PANS

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U2 - 10.1016/j.biopsych.2024.09.004

DO - 10.1016/j.biopsych.2024.09.004

M3 - Journal article

C2 - 39284402

AN - SCOPUS:85208684690

SN - 0006-3223

VL - 97

SP - 672

EP - 677

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 7

ER -

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

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