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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating evidence suggests that prenatal exposure to infection contributes to the etiology of schizophrenia. This line of investigation has been advanced by birth cohort studies that utilize prospectively acquired data from serologic assays for infectious and immune biomarkers. These investigations have provided further support for this hypothesis and permitted the investigation of new infectious pathogens in relation to schizophrenia risk. Prenatal infections that have been associated with schizophrenia include rubella, influenza, and toxoplasmosis. Maternal cytokines, including interleukin-8, are also significantly increased in pregnancies giving rise to schizophrenia cases. Although replication of these findings is required, this body of work may ultimately have important implications for the prevention of schizophrenia, the elaboration of pathogenic mechanisms in this disorder, and investigations of gene-environment interactions.
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PMID:Prenatal infection as a risk factor for schizophrenia. 1646 41

The prevalence of schizophrenic disorders in the general population is 1%, that is, in France, approximately 40000 people, given the age group concerned. The sex ratio is one. The first episode occurs between the ages of 15 and 25 years in men, a little later in women. 90% of patients treated for schizophrenia are aged from 15 to 55 years. The short-term course is marked by a relapse rate after the first episode estimated at 20-40%. The long-term evolution is marked by substantial excess mortality, a suicide rate of 10-20% and an overall decrease of approximately 10 years in life expectancy. Only 10% of patients will have an outcome including full autonomy. The socioeconomic impact is therefore considerable, with a mean cost of management estimated at 15000 Euros per year. Genetic factors affect vulnerability or predisposition to schizophrenia. Accordingly a first-degree relative of a schizophrenic patient has a risk 5 to 10 times higher of developing the disease than does a person with no affected relatives. This risk is not one of simple Mendelian transmission but rather vulnerability, which implies the intervention of several genes. Some environmental factors have also been identified, including exposure to influenza virus during the gestational period (between the 4th and 7th month of pregnancy). This finding reinforces the hypothesis of a neurodevelopmental origin of schizophrenia. Finally, among other associated factors, regular cannabis use appears to quadruple the risk of disease.
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PMID:[Epidemiology of schizophrenic disorders]. 1655 Jan 42

An episode of hyperthermia is not uncommon during pregnancy. The consequences depend on the extent of temperature elevation, its duration, and the stage of development when it occurs. Mild exposures during the preimplantation period and more severe exposures during embryonic and fetal development often result in prenatal death and abortion. Hyperthermia also causes a wide range of structural and functional defects. The central nervous system (CNS) is most at risk probably because it cannot compensate for the loss of prospective neurons by additional divisions by the surviving neuroblasts and it remains at risk at stages throughout pre- and postnatal life. In experimental animals the most common defects are of the neural tube, microphthalmia, cataract, and micrencephaly, with associated functional and behavioral problems. Defects of craniofacial development including clefts, the axial and appendicular skeleton, the body wall, teeth, and heart are also commonly found. Nearly all these defects have been found in human epidemiological studies following maternal fever or hyperthermia during pregnancy. Suggested future human studies include problems of CNS function after exposure to influenza and fever, including mental retardation, schizophrenia, autism, and cerebral palsy.
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PMID:Review: Hyperthermia and fever during pregnancy. 1693 4

Proof of causality of most neuromental disorders (NMD's) is largely unavailable. Lessons from four-decade investigations of the epidemiology, immunology, pathogenesis, prevention and therapy of perinatal infectious agents, which invade directly the nervous system, have led us to propose a new indirect effect hypothesis: maternal transplacentally-acquired antibodies, to agents with epitope molecular mimicry with the developing nervous system, can cross the fetus/infant's blood-nervous system barriers to cause NMD's, clinically manifest years later. Further rationale is provided by relevant evolutionary/developmental (EVO-DEVO) considerations - applicable also to some vaccines. The hypothesis is being tested in: (a) older pregnancy studies with available maternal and newborn sera, and follow-up of the progeny for NMD's; and (b) NMD registry individuals linked to their stored newborn blood spots. Preliminary results support a possible role for schizophrenia of high-tittered antibodies to some agents (toxoplasma, influenza and herpes simplex type 2 virus). A model that includes likely genetic and postnatal influences is schematized and a list of putative agents and factors, based on varying rationales, is tabulated. In case pilot studies are confirmed, the identified agent(s) and antibodies would need to be tested in new prospectively enrolled pregnant women, so as to establish further risk factors leading to possible preventive modalities.
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PMID:The possible role of transplacentally-acquired antibodies to infectious agents, with molecular mimicry to nervous system sialic acid epitopes, as causes of neuromental disorders: prevention and vaccine implications. 1716 60

A hypothesis is presented that the association between maternal influenza and other causes of fever during the second trimester of pregnancy and the subsequent development of schizophrenia in the child is due to the damage caused by hyperthermia to the developing amygdalohippocampal complex and associated structures in the fetal brain. Hyperthermia is a known cause of congenital defects of the central nervous system and other organs after sufficiently severe exposures during early organogenesis. The pathogenic mechanisms include death of actively dividing neuroblasts, disruption of cell migration and arborization and vascular damage. In experimental studies, hyperthermia during later stages of central nervous system development also caused damage to the developing brainstem that was associated with functional defects. This damage usually results in hypoplasia of the parts undergoing active development at the time of exposure. Recent studies have shown no evidence of direct invasion of the fetus by the influenza virus. Factors that might interact with hyperthermia include familial liability to schizophrenia, season of birth, maternal nutrition, severe stress and medications used to alleviate the symptoms of fevers. The time of the development of the fetal amygdalohippocampal complex and the changes found in its structure and associated areas of the brain are compatible with the known effects of hyperthermia.
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PMID:Hyperthermia in utero due to maternal influenza is an environmental risk factor for schizophrenia. 1768 66

A range of complications of pregnancy, abnormal fetal growth and development, and complications of delivery have been associated with increased risk of schizophrenia. Few studies have been able to adjust for a broad range of potential confounding factors. A national population nested case-control study based on Danish longitudinal registers was conducted to investigate the risk of schizophrenia associated with exposure to a range of obstetric events. The sample included 1039 first admissions to, or contacts with Danish psychiatric services with an ICD-8 or ICD-10 diagnosis of schizophrenia and 24, 826 individually matched controls. Adjusting for the other obstetric factors, family psychiatric history, and socio-economic and demographic factors, risk of schizophrenia was associated with maternal non-attendance at antenatal appointments (Incidence Rate Ratio (IRR) 2.08, 95% CI: 1.0, 4.4), gestational age of 37 weeks or below (IRR 1.51, 95% CI: 1.0, 2.2), maternal influenza (IRR 8.2, 95% CI: 1.4, 48.8), preeclampsia (IRR 2.72, 95% CI: 1.0, 7.3), threatened premature delivery (IRR 2.39, 95% CI: 1.4, 4.1), haemorrhage during delivery (IRR 2.43, 95% CI: 1.1, 5.6), manual extraction of the baby (IRR 2.15, 95% CI: 1.1, 4.4), and maternal sepsis of childbirth and the puerperium (IRR 2.91, 95% CI: 1.1, 7.9). There was no significant interaction between the obstetric factors and either sex or family psychiatric history. The data suggest a modest association between prematurity, indicators of hypoxia, maternal infections, and maternal behaviours and risk of the later development of schizophrenia after adjusting for a number of possible confounding factors.
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PMID:Obstetric conditions and risk of first admission with schizophrenia: a Danish national register based study. 1776 5

Influenza is an infectious disease which often occurs during pregnancy. Publications on this matter from the magazines Medline, Cochrane library, Nature, Science, Lancet, GyneWeb and others are discussed to determine the impact of this disease on the pregnant and the embryo, possible complications and means of prevention. It has been established that influenza results sometimes in serious injuries to the pregnant and embryo, among which is also schizophrenia. Opportunities for vaccination of the pregnant and practices applied in such cases in other countries are discussed.
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PMID:[Influenza and pregnancy]. 1797 70

Prenatal viral infection has been associated with development of schizophrenia and autism. Our laboratory has previously shown that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) administration of influenza virus. We hypothesized that late second trimester infection (E18) in mice may lead to a different pattern of brain gene expression and structural defects in the developing offspring. C57BL6J mice were infected on E18 with a sublethal dose of human influenza virus or sham-infected using vehicle solution. Male offsping of the infected mice were collected at P0, P14, P35 and P56, their brains removed and prefrontal cortex, hippocampus and cerebellum dissected and flash frozen. Microarray, qRT-PCR, DTI and MRI scanning, western blotting and neurochemical analysis were performed to detect differences in gene expression and brain atrophy. Expression of several genes associated with schizophrenia or autism including Sema3a, Trfr2 and Vldlr were found to be altered as were protein levels of Foxp2. E18 infection of C57BL6J mice with a sublethal dose of human influenza virus led to significant gene alterations in frontal, hippocampal and cerebellar cortices of developing mouse progeny. Brain imaging revealed significant atrophy in several brain areas and white matter thinning in corpus callosum. Finally, neurochemical analysis revealed significantly altered levels of serotonin (P14, P35), 5-Hydroxyindoleacetic acid (P14) and taurine (P35). We propose that maternal infection in mouse provides an heuristic animal model for studying the environmental contributions to genesis of schizophrenia and autism, two important examples of neurodevelopmental disorders.
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PMID:Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. 1824 90

Schizophrenia and autism are neurodevelopmental diseases that have genetic as well as environmental etiologies. Both disorders have been associated with prenatal viral infection. Brain imaging and postmortem studies have found alterations in the structure of the cerebellum as well as changes in gene expression. Our laboratory has developed an animal model using prenatal infection of mice with human influenza virus that has demonstrated changes in behavior, pharmacology, structure, and gene expression in the brains of exposed offspring. In the current communication we describe altered expression of cerebellar genes associated with development of brain disorder in a mouse model for schizophrenia and autism and correlate these changes with those involved in the pathology of these two disorders.
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PMID:The role of cerebellar genes in pathology of autism and schizophrenia. 1841 86

The neurodevelopmental hypothesis of schizophrenia proposes that a portion of schizophrenia is the result of an early brain insult which affects brain development and in which several types of virus might play an etiological role. The main arguments in favor of the neurodevelopmental hypothesis and the involvement of prenatal exposure to virus infection as a risk factor for adult schizophrenia are reviewed. Schizophrenia is associated with an increased incidence of craniofacial asymmetries and dermatoglyphic irregularities which might reflect an abnormal development of the ectoderm and the neural crest as a result of a viral infection between the first and second trimester of pregnancy. The brain histology of deceased schizophrenic patients shows disturbed neuronal migration and formations such as disorganized lamina strata or ectopic pyramidal cells, abnormal expression of the neural cell adhesion molecule, and absence of gliosis. The main epidemiological arguments are derived from studies of obstetrical complications and influenza virus infection during pregnancy, both considered to be early risk factors of schizophrenia. Because no virus has been consistently linked with the pathogenesis of schizophrenia, the most plausible hypothesis is that an endemic virus could initiate schizophrenia by direct brain lesion or by triggering an autoimmune response during the neurodevelopmental period on a genetically susceptible brain. In a neurodevelopmental model, the viral hypothesis is a step toward the goal of building a comprehensive theory that integrates the environmental, genetic, immune, and neuropsychological features of schizophrenia.
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PMID:Schizophrenia and viral infection during neurodevelopment: a pathogenesis model? 1850 85


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