Infections of the central nervous system as a risk factor for mental disorders and cognitive impairment: A nationwide register-based study

Pedersen, Emilie M.J.; Köhler‐Forsberg, Ole; Nordentoft, Merete; Christensen, Rune Haubo Bojesen; Mortensen, Preben Bo; Petersen, Liselotte; Benros, Michael E.

doi:10.1016/j.bbi.2020.04.072

Cited by 18 publications

(18 citation statements)

References 29 publications

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“…More recently, Sabourin and co-workers reported that individuals with ASD were more likely to have had an infection during the first three years of life than comparison individuals using a combination of neonatal records and care-giver interviews prone to bias 31 . Our observations regarding CNS-infections agree with those reported by Pedersen et al 18 , who found a weak association between CNS-infections and ASD that disappeared after exclusion of individuals with co-occurring ID, although we lacked power to distinguish between effects of CNS and non-CNS infections.…”

Section: Discussionsupporting

confidence: 90%

“…With regard to the observed risk for ID, our results are in agreement with a number of clinical follow-up studies of neonates with congenital infections 13 and CNS-infections 40 of both viral and bacterial origin during both infancy and childhood 14-16, 41-43 . In a study employing Danish population registers 18 , the authors explored a wide range of mental disorders in relation to previous CNS infections and reported a significant association (HR 3.29) between CNS-infections and later ID, similar to those observed here for ‘ID without ASD’ (HR 3.66) and for ‘ASD with ID’ (HR 3.21).…”

Section: Discussionsupporting

confidence: 67%

“…Infections that can invade the fetal brain are established causes of life-long behavioral and intellectual disabilities 12,13 . Infections targeting the brain during childhood have also been associated with cognitive impairments and psychiatric illness which become evident only later in life [14][15][16][17][18] . A growing literature associates childhood infections with no apparent CNS involvement with schizophrenia risk in adulthood [19][20][21][22] , with a significant portion of risk mediated by reduced cognitive abilities 21 .…”

Section: Introductionmentioning

confidence: 99%

“…Observations of deficits in innate immunity among neonates who later develop schizophrenia 23 or ASD 24 further highlight the potential contribution of postnatal infections to these outcomes 25-27 . However, only a handful of studies, with equivocal results, have investigated the relationship between childhood infections and the risk of ASD 18, 28-31 .…”

Section: Introductionmentioning

confidence: 99%

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Infections in childhood and subsequent diagnosis of autism spectrum disorders and intellectual disability: a register-based cohort study

Karlsson

Sjöqvist

Brynge

et al. 2021

Preprint

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Objective. To explore the associations between childhood infections and subsequent diagnoses of autism spectrum disorder (ASD), intellectual disability (ID) and their co-occurrence. Methods. The association between specialized care for any infection, defined by ICD-codes and later ASD or ID was investigated in a register-based cohort of 556,732 individuals born 1987-2010, resident in Stockholm County, followed from birth to their 18th birthday or December 31, 2016. We considered as potential confounders childrens characteristics, family socioeconomic factors, obstetric complications, and parental histories of both treatment for infection and psychiatric disorders in survival analyses with extended Cox regression models. Residual confounding by shared familial factors was addressed in sibling analyses using within-strata estimation in Cox regression models. Sensitivity analyses with exclusion of congenital causes of ASD/ID and documented risk for infections were also performed. Results. Crude estimates indicated that infections during childhood were associated with later ASD and ID with largest risks observed for diagnoses involving ID. Inclusion of covariates, exclusion of congenital causes of ASD/ID from the population and sibling comparisons highlighted the potential for confounding by both heritable and non-heritable factors, though risks remained in all adjusted models. In adjusted sibling comparisons, excluding congenital causes, infections were associated with later ASD without ID (HR 1.24, 95%CI 1.15-1.33), ASD with ID (1.57, 1.35-1.82) and ID without ASD (2.01, 1.76-2.28). Risks associated with infections varied by age at exposure and by age at diagnosis of ASD/ID. Conclusions. Infections during childhood cannot be excluded in the etiology of ASD, particularly ASD with co-occurring ID.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Infections in childhood and subsequent diagnosis of autism spectrum disorders and intellectual disability: a register-based cohort study

Karlsson

Sjöqvist

Brynge

et al. 2021

Preprint

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“…Infections that can invade the fetal and neonatal brain are established causes of life-long behavioral and intellectual disabilities [14,15]. Infections during childhood have also been associated with psychiatric illness, including ID, later in life [16][17][18][19][20]. The extent to which some of these associations are causal or confounded by the genetic causes of ID or other psychiatric outcomes is currently not known.…”

Section: Introductionmentioning

confidence: 99%

Childhood infections and autism spectrum disorders and/or intellectual disability: a register-based cohort study

Karlsson

Sjöqvist

Brynge

et al. 2022

J Neurodevelop Disord

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Objective To explore the associations between childhood infections and subsequent diagnoses of autism spectrum disorder (ASD), intellectual disability (ID), and their co-occurrence. Methods The association between specialized care for any infection, defined by ICD-codes, and later ASD or ID was investigated in a register-based cohort of 556,732 individuals born 1987–2010, resident in Stockholm County, followed from birth to their 18th birthday or December 31, 2016. We considered as potential confounders children’s characteristics, family socioeconomic factors, obstetric complications, and parental histories of treatment for infection and psychiatric disorders in survival analyses with extended Cox regression models. Residual confounding by shared familial factors was addressed in sibling analyses using within-strata estimation in Cox regression models. Sensitivity analyses with the exclusion of congenital causes of ASD/ID and documented risk for infections were also performed. Results Crude estimates indicated that infections during childhood were associated with later ASD and ID with the largest risks observed for diagnoses involving ID. Inclusion of covariates, exclusion of congenital causes of ASD/ID from the population, and sibling comparisons highlighted the potential for confounding by both heritable and non-heritable factors, though risks remained in all adjusted models. In adjusted sibling comparisons, excluding congenital causes, infections were associated with later “ASD without ID” (HR 1.24, 95%CI 1.15–1.33), “ASD with ID” (1.57, 1.35–1.82), and “ID without ASD” (2.01, 1.76–2.28). Risks associated with infections varied by age at exposure and by age at diagnosis of ASD/ID. Conclusions Infections during childhood may contribute to a later diagnosis of ID and ASD.

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Psychiatric Medication Use After Possible Neuroborreliosis

2021

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Dr Fallon and Benros are currently conducting a study of the association with mental disorders and suicidality after Lyme borreliosis, with, among others, funding from the Global Lyme Alliance Inc. The funders had no role in the scientific process, interpretation of the results, or the decision to publish this letter or other research. No other disclosures were reported. 1. Tetens MM, Haahr R, Dessau RB, et al. Assessment of the risk of psychiatric disorders, use of psychiatric hospitals, and receipt of psychiatric medication among patients with Lyme neuroborreliosis in Denmark. JAMA Psychiatry.

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Infections of the central nervous system as a risk factor for mental disorders and cognitive impairment: A nationwide register-based study

Cited by 18 publications

References 29 publications

Infections in childhood and subsequent diagnosis of autism spectrum disorders and intellectual disability: a register-based cohort study

Infections in childhood and subsequent diagnosis of autism spectrum disorders and intellectual disability: a register-based cohort study

Childhood infections and autism spectrum disorders and/or intellectual disability: a register-based cohort study

Psychiatric Medication Use After Possible Neuroborreliosis

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