Exposure to Prenatal and Childhood Infections and the Risk of Schizophrenia

Westergaard, Tine; Mortensen, Preben Bo; Pedersen, Carsten Bøcker; Wohlfahrt, Jan; Melbye, Mads

doi:10.1001/archpsyc.56.11.993

Cited by 122 publications

(35 citation statements)

References 48 publications

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“…A larger study by Adams et al, 8 which included the birth cohort studied by Barr et al, found no such association. Takei et al 39 found an increased risk for subjects exposed 4 months prior to birth (RR = 1.12, 95% CI: 1.00-1.21), but Westergaard et al 40 could not replicate the findings of Takei et al even when they employed their methods and concluded that there was no association between schizophrenia risk and influenza prevalence during any month of prenatal life.…”

Section: Studies Not Related To 1957 Pandemicmentioning

confidence: 95%

“…18 Finally, 4 studies examined the relationship between the prevalence of influenza and the risk of schizophrenia in Denmark. 8,[38][39][40] Each study used a different method and covered a different birth period (1911-1950, 1911-1965, 1915-1970, and 1950-1984, respectively). Barr et al 38 reported an association between schizophrenia risk and relatively high levels of influenza exposure for the season during the sixth month of gestation but did not mention a RR.…”

Section: Studies Not Related To 1957 Pandemicmentioning

confidence: 99%

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Schizophrenia and 1957 Pandemic of Influenza: Meta-analysis

Selten

Frissen

Lensvelt-Mulders

et al. 2009

Schizophrenia Bulletin

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Maternal influenza during pregnancy is a controversial risk factor for schizophrenia in the child. We conducted a meta-analysis to examine whether birth during the 9-month period after the pandemic of 1957 was a risk factor for schizophrenia. Studies that compared the risk of schizophrenia among subjects born after the pandemic with that among those born in corresponding time periods in surrounding years were divided into those conducted in the United States, Europe, or Australia (type A studies, n 5 8) and those from Japan, where the epidemic came in 2 waves (type B studies, n 5 3). Other studies examined the risk among subjects born to mothers who were pregnant during the pandemic and reported having had influenza (type C studies, n 5 2). Relative risks (RRs) were extracted or calculated for each month and/or trimester of possible exposure by 2 independent authors. All analyses were performed using a fixed-effects model. The weighted results of the type A studies did not indicate a significantly increased risk of schizophrenia among children exposed during any trimester or month of prenatal life. Not a single study found a significant first-or second-trimester effect. The mean weighted RR for subjects who were in their first, second, or third trimester of prenatal life during the pandemic (8 effect sizes) was 0.91 (95% confidence interval [CI]: 0.85-0.98), 1.00 (95% CI: 0.93-1.07), and 1.05 (95% CI: 0.98-1.12), respectively. The pooled results of the type B and type C studies were also negative. Given high infection rates during the pandemic (about 50%), these results do not support the maternal influenza hypothesis.

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Section: Studies Not Related To 1957 Pandemicmentioning

confidence: 95%

Section: Studies Not Related To 1957 Pandemicmentioning

confidence: 99%

Schizophrenia and 1957 Pandemic of Influenza: Meta-analysis

Selten

Frissen

Lensvelt-Mulders

et al. 2009

Schizophrenia Bulletin

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“…Only parents whose children were over the age of 15 years at the termination of follow-up on 31 December 1997 were included since less than 1.5% of schizophrenia cases develop before that age (Westergaard et al, 1999). The CPR was established in 1968 and all residents of Denmark were assigned a unique identification number that permits accurate linkage between registries.…”

Section: Methodsmentioning

confidence: 99%

Major life event – diagnosis of schizophrenia in offspring and risk for cancer

et al. 2004

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The overall risk for cancer among 19 856 parents of schizophrenic patients in Denmark was not increased; however, a 30% increased risk for lung cancer was observed in mothers (95% confidence interval, 1.03 -1.61), suggesting an indirect effect on cancer risk mediated by life-style factors. The belief that psychological stress causes cancer has a long history, but scientific evidence remains contradictory to date (Fox, 1995;Dalton et al, 2002). Psychological stress has effects on the endocrine and immune systems, which might enhance neoplastic growth by increasing the levels of corticosterone, prolactin or estrogen, or by decreasing the number and activity of lymphocytes and natural killer cells (Ader et al, 1995;Kiecolt-Glaser et al, 2002). Stress could also increase adverse life-style behaviours like smoking and heavy alcohol drinking, which over time increase cancer incidence (Smith and Gallo, 2000).A son or daughter with severe mental illness, such as schizophrenia, is associated with significant grief, sorrow and feeling of loss constituting psychological distress among family members (Czuchta and McCay, 2001;Martens and Addington, 2001). We investigated the effect of the diagnosis of schizophrenia in a son or daughter as an indicator of psychological stress on overall and specific cancer incidence among their parents in a population-based study based on nationwide registers with complete and unbiased information on both exposure and outcomes of interest. MATERIALS AND METHODSFrom the nationwide Danish Central Population Register (CPR) we identified all 2 013 848 parents born in Denmark, alive on 1 April 1969 whose children were born after 1935 and were living between 1 April 1969 and 1 January 1983. Only parents whose children were over the age of 15 years at the termination of follow-up on 31 December 1997 were included since less than 1.5% of schizophrenia cases develop before that age (Westergaard et al, 1999). The CPR was established in 1968 and all residents of Denmark were assigned a unique identification number that permits accurate linkage between registries.By linkage to the nationwide Danish Psychiatric Central Register, which contains information on all psychiatric admissions since 1969 (Munk-Joergensen and Mortensen, 1997), we identified and excluded 6676 parents who had been admitted for schizophrenia according to the International Classification of Diseases 8th revision between 1969 and 1993 (ICD-8, 295) and the 10th revision between 1993 and 1997 (ICD-10, F20; F25). Further, 10 466 offspring of the remaining parents were identified in the Danish Psychiatric Central Register with a diagnosis of schizophrenia; their parents constituted the exposed cohort.We used the nationwide Danish Cancer Registry, which contains information on all cancer diagnosed in Denmark since 1943 coded according to a modified Danish version of the ICD-7 (Storm et al, 1997), to identify parents who developed a first primary cancer between 1 April 1969 or the day when the offspring reached 15 years (study entry), whichev...

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“…Beginning in the 1980s, most studies [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25] used an ecological design and estimated the timing of the exposure to infectious agents in populations by obtaining retrospective data on epidemics from registries. Some studies [26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41] additionally collected exposure data by interviewing mothers during or shortly after pregnancy or using their medical records.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Inflammation, Infections and Mental Disorders

Flinkkilä

Keski‐Rahkonen

Marttunen³

et al. 2016

Psychopathology

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Background: The objective of this descriptive review is to summarize the current scientific evidence on the effect of prenatal exposure to maternal infection and immune response on the offspring's risk for mental disorders (schizophrenia spectrum disorders, autism spectrum disorders, attention-deficit hyperactivity disorder, anorexia nervosa, and mood disorders). Sampling and Methods: Studies were searched from PubMed and Ovid MEDLINE (R) databases with the following keywords: ‘prenatal exposure delayed effects' and ‘infection', and ‘inflammation' and ‘mental disorders'. A comprehensive manual search, including a search from the reference list of included articles, was also performed. Results: Prenatal exposure to maternal influenza appears to increase the offspring's risk for schizophrenia spectrum disorders, although studies are not fully consistent. Prenatal exposure to maternal fever and elevated cytokine levels seems to be related to the elevated risk for autism spectrum disorders in the offspring. No replicated findings of an association between prenatal infectious exposure and other mental disorders exist. Conclusions: Evidence for the effect of prenatal exposure to maternal infection on risk for mental disorders exists for several different infections, suggesting that common factors occurring in infections (e.g. elevated cytokine levels and fever), rather than the infectious agent itself, might be the underlying factor in increasing the risk for mental disorders. Additionally, it is likely that genetic liability to these disorders operates in conjunction with the exposure. Therefore, genetically sensitive study designs are needed in future studies.

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Exposure to Prenatal and Childhood Infections and the Risk of Schizophrenia

Cited by 122 publications

References 48 publications

Schizophrenia and 1957 Pandemic of Influenza: Meta-analysis

Schizophrenia and 1957 Pandemic of Influenza: Meta-analysis

Major life event – diagnosis of schizophrenia in offspring and risk for cancer

Prenatal Inflammation, Infections and Mental Disorders

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