Infections in the CNS During Childhood and the Risk of Subsequent Psychotic Illness: A Cohort Study of More Than One Million Swedish Subjects

Dalman, Christina; Allebeck, Peter; Gunnell, David; Harrison, G; Kristensson, Krister; Lewis, Glyn; Löfving, Sofia; Rasmussen, Finn; Wicks, Susanne; Karlsson, Håkan

doi:10.1176/appi.ajp.2007.07050740

Cited by 214 publications

(144 citation statements)

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“…Causes of HI in young people that may also have an impact on the risk for psychotic experiences include birth trauma (Herrgard et al 1995) and prenatal and postnatal exposure to infections (Dalman et al 2008 ;Zammit et al 2009). Rubella and meningitis may harm the developing central nervous system, and exposure has been associated with an increased risk for both hearing deficits (Fortnum & Davis, 1993) and psychosis (Brown et al 2000 ;Leask et al 2002 ;Dalman et al 2008). Thus, HI and psychosis may be the result of a single underlying causative mechanism.…”

Section: Hi and Psychosis : A Shared Cause ?mentioning

confidence: 99%

“…First, HI and psychosis may be the consequence of a common underlying cause. For example, exposure to perinatal infections affecting the central nervous system, such as rubella and meningitis (Brown et al 2000 ;Leask et al 2002 ;Dalman et al 2008), may explain the association between early HI and later psychosis. Second, psychotic experiences may be a direct or indirect consequence of processes triggered by hearing loss.…”

Section: Introductionmentioning

confidence: 99%

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Adolescent development of psychosis as an outcome of hearing impairment: a 10-year longitudinal study

et al. 2010

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Background. It has long been acknowledged that hearing impairment may increase the risk for psychotic experiences. Recent work suggests that young people in particular may be at risk, indicating a possible developmental mechanism.Method. The hypothesis that individuals exposed to hearing impairment in early adolescence would display the highest risk for psychotic symptoms was examined in a prospective cohort study of a population sample of originally 3021 adolescents and young adults aged 14-24 years at baseline, in Munich, Germany (Early Developmental Stages of Psychopathology Study). The expression of psychosis was assessed at multiple time points over a period of up to 10 years, using a diagnostic interview (Munich Composite International Diagnostic Interview ; CIDI) administered by clinical psychologists.Results. Hearing impairment was associated with CIDI psychotic symptoms [odds ratio (OR) 2.04, 95 % confidence interval (CI) 1.10-3.81], particularly more severe psychotic symptoms (OR 5.66,). The association between hearing impairment and CIDI psychotic symptoms was much stronger in the youngest group aged 14-17 years at baseline (OR 3.28, 95 % CI 1.54-7.01) than in the older group aged 18-24 years at baseline (OR 0.82, 95 % CI 0.24-2.84).Conclusions. The finding of an age-specific association between hearing impairment and psychotic experiences suggests that disruption of development at a critical adolescent phase, in interaction with other personal and social vulnerabilities, may increase the risk for psychotic symptoms.

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Section: Hi and Psychosis : A Shared Cause ?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adolescent development of psychosis as an outcome of hearing impairment: a 10-year longitudinal study

et al. 2010

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“…Epidemiological studies have shown that infections and autoimmune diseases are clin ic ally important risk factors for the development of schizo phrenia. [1][2][3] Furthermore, a recent study integrating results from a meta analysis of genome wide association studies in schizophrenia found that the most significant changes were observed in genetic loci related to the immune system. 4 Also, patients with schizophrenia show microglial activation, as re vealed by positron emission tomography.…”

Section: Introductionmentioning

confidence: 99%

Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia — significance for activation of the kynurenine pathway

Schwieler

Larsson

Skogh

et al. 2015

jpn

188

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IntroductionThe role of immune activation in schizophrenia has received increasing interest in recent years. Epidemiological studies have shown that infections and autoimmune diseases are clin ic ally important risk factors for the development of schizo phrenia. [1][2][3] Furthermore, a recent study integrating results from a meta analysis of genome wide association studies in schizophrenia found that the most significant changes were observed in genetic loci related to the immune system. 4 Also, patients with schizophrenia show microglial activation, as re vealed by positron emission tomography. 5,6 Further, postmor tem studies using messenger RNA (mRNA) expression or im munohistochemical detection have shown increased levels of immune related compounds. 7-9 A number of investigations have focused on cytokines, but these studies have not yielded a unanimous picture, possibly because of a number of con founding factors, such as smoking and dietary habits, body mass index (BMI), type and duration of antipsychotic treat ment and drug abuse -all factors potentially affecting the Background: Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway. Methods: We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were ana lyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry. Results: We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA. Limitations: The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age. Conclusion: We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-d-aspartate receptor antagonist KYNA in patients with schizophrenia.

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“…More recently, it has been suggested that central nervous system infections of cytomegalovirus or mumps virus in childhood may also increase the risk for schizophrenia (Dalman et al, 2008). All of these factors have been shown to affect mitochondria, inducing strong intracellular oxidative stress and/or apoptosis (Akaike et al, 1990;Edlund et al, 1994;Speir et al, 1998;He et al, 2003;Berger et al, 2004;Zaki et al, 2005;Gupta et al, 2004;Kruman et al, 2006;Wang et al, 2006;Poncet et al, 2006;Chang et al, 2007;Nishikawa et al, 2007).…”

Section: Prenatal Risk Factors For Schizophreniamentioning

confidence: 99%

Impact of Epidemiology on Molecular Genetics of Schizophrenia

Doi¹,

Hoshi²,

Itokawa³

et al. 2012

Epidemiology Insights

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Infections in the CNS During Childhood and the Risk of Subsequent Psychotic Illness: A Cohort Study of More Than One Million Swedish Subjects

Abstract: Serious viral CNS infections during childhood appear to be associated with the later development of schizophrenia and nonaffective psychoses. The association with specific viruses suggests that the risk is related to infectious agents with a propensity to invade the brain parenchyma.

Cited by 214 publications

References 41 publications

Adolescent development of psychosis as an outcome of hearing impairment: a 10-year longitudinal study

Adolescent development of psychosis as an outcome of hearing impairment: a 10-year longitudinal study

Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia — significance for activation of the kynurenine pathway

Impact of Epidemiology on Molecular Genetics of Schizophrenia

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