Adult Schizophrenia Following Prenatal Exposure to an Influenza Epidemic

Mednick, Sarnoff A.; Machón, Ricardo A.; Huttunen, Matti; Bonett, Douglas G.

doi:10.1001/archpsyc.1988.01800260109013

Cited by 1,084 publications

(495 citation statements)

References 13 publications

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“…Lloyd found that overall facial asymmetry, asymmetry of the orbital landmarks, as well as other abnormalities distinguished patients with schizophrenia and affective psychosis from controls, suggesting an insult during organogenesis in the first trimester of pregnancy (Lloyd et al, 2007). Despite these findings most of the epidemiological evidence points to infection during the 2 nd trimester to be responsible for the development of schizophrenia in offspring (Mednick et al 1988;Barr et al 1990;Mednick et al 1994;Kungi et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Viral regulation of aquaporin 4, connexin 43, microcephalin and nucleolin

Fatemi¹,

Folsom²,

Reutiman³

et al. 2008

Schizophrenia Research

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The current study investigated whether human influenza viral infection in midpregnancy leads to alterations in proteins involved in brain development. Human influenza viral infection was administered to E9 pregnant Balb/c mice. Brains of control and virally exposed littermates were subjected to microarray analysis, SDS-PAGE and western blotting at three postnatal stages. Microarray analysis of virally-exposed mouse brains showed significant, two-fold change in expression of multiple genes in both neocortex and cerebellum when compared to sham-infected controls. Levels of mRNA and protein levels of four selected genes were examined in brains of exposed mice. Nucleolin mRNA was significantly decreased in day 0 and day 35 neocortex and significantly increased in day 35 cerebellum. Protein levels were significantly upregulated at days 35 and 56 in neocortex and at day 56 in cerebellum. Connexin 43 protein levels were significantly decreased at day 56 in neocortex. Aquaporin 4 mRNA was significantly decreased in day 0 neocortex. Aquaporin 4 protein levels decreased in neocortex significantly at day 35. Finally, microcephalin mRNA was significantly decreased in day 56 neocortex and protein levels were significantly decreased at 56 cerebellum. These data suggest that influenza viral infection in midpregnancy in mice leads to long term changes in brain markers for enhanced ribosome genesis (nucleolin), increased production of immature neurons (microcephalin), and abnormal glial-neuronal communication (connexin 43 and aquaporin 4).

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Section: Discussionmentioning

confidence: 99%

Viral regulation of aquaporin 4, connexin 43, microcephalin and nucleolin

Fatemi¹,

Folsom²,

Reutiman³

et al. 2008

Schizophrenia Research

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“…Mednick and colleagues 19 first reported an increased risk of schizophrenia among individuals exposed prenatally to the 1957 influenza epidemic in Helsinki. Most subsequent studies examining this issue have found a positive association but there have also been some negative findings (Brown 20 provides an extensive review of this literature).…”

Section: Prenatal Infectionmentioning

confidence: 99%

“…37 Animal models of prenatal stress have informed our understanding of the mechanisms at play. For example, it has been shown in humans that the greatest sensitivity of the developing fetus to stress is likely to be during late first or second trimester of pregnancy, 19 when, based on animal evidence, glucocorticoid receptor expression is commencing in the developing fetal brain. The precise timing of glucocorticoid receptor expression in the developing human brain, however, is currently unknown.…”

Section: Prenatal Stressmentioning

confidence: 99%

Predicting Risk and the Emergence of Schizophrenia

Clarke

Kelleher

Clancy

et al. 2012

Psychiatric Clinics of North America

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“…A causal relationship pertaining to disturbed brain ontogenesis and schizophrenia comes from epidemiological studies that have identified several risk factors that, acting during pregnancy, increase the incidence of the disease in offspring. Maternal infection with influenza virus in the second trimester of pregnancy causes a major disorder incidence (Mednick et al 1988;O'Callaghan et al 1991;Adams et al 1993). In addition, a seasonal effect has been also documented, with more persons born in the late winter and early spring months developing schizophrenia (Torrey et al 1977;Mortensen et al 1999).…”

mentioning

confidence: 99%

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

Borrell

Vela²,

Arévalo-Martı́n³

et al. 2002

Neuropsychopharmacology

280

191

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Increasing evidence associates schizophrenia with prenatal exposure to infection. Impaired ability to "gate out" sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition (PPI) of the acoustic startle reflex. We analyzed the effect of a prenatal immune challenge-peripheral administration of bacterial endotoxin lipopolysaccharide (LPS) to pregnant female rats-upon PPI and immune function in adult offspring. Prenatal LPS treatment disrupted PPI which was reversed by antipsychotics. Serum levels of interleukin-2 and interleukin-6 were increased. In addition, histopathological features in brain areas related with PPI circuitry were observed. These results illustrate the critical influence of prenatal immune events upon adult CNS functioning in association with the putative role of the immune system in (Braff et al. 1978;Kumari et al. 1999). A well-established sensorimotor gating paradigm is the prepulse inhibition (PPI) of the startle response. PPI refers to the reduction in startle reactivity toward an intense pulse stimulus when it is shortly preceded by a weak prepulse stimulus (Hoffman and Ison 1980). It is thought that the prepulse response activates an inhibitory process that attenuates or "gates" the startle response. Because identical stimulus parameters can be used for animal and human studies, it is considered that animal models of PPI disruption represent a promising way to study the neural mechanisms underlying sensorimotor gating dysfunction (Swerdlow et al. 1994(Swerdlow et al. , 1999Swerdlow and Geyer 1998) and as a screening test for potential antipsychotics (Swerdlow et al. 1994;Depoortere et al. 1997). In fact, antipsychotics remove PPI deficits in schizophrenic patients (Kumari et al. 1999;Weike et al. 2000). Nevertheless, it must be taken into consideration that deficiency of PPI has been reported in other selected neuropsychiatric disorders where inability to inhibit movements is involved (Huntington's disease (Swerdlow et al. 1995 Tourette's syndrome (Castellanos et al. 1996)), where inability to control attentional and cognitive processes is involved (obsessive-compulsive disorder (Swerdlow et al. 1993)), or where anxiety and exaggerated startle occur (posttraumatic stress disorder (Grillon et al. 1996)). The focus of schizophrenia research has been turning from studies of structural and functional brain abnormalities to an increasing emphasis on possible etiologic factors. Neurodevelopmental theories of schizophrenia postulate that the psychopathology of schizophrenia may derive from alterations of brain organization secondary to defective ontogenesis (Weinberger 1996;Raedler et al. 1998). A causal relationship pertaining to disturbed brain ontogenesis and schizophrenia comes from epidemiological studies that have identified several risk factors that, acting during pregnancy, increase the incidence of the disease in offspring. Maternal infection with influenza virus in the second trimester of preg...

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Adult Schizophrenia Following Prenatal Exposure to an Influenza Epidemic

Cited by 1,084 publications

References 13 publications

Viral regulation of aquaporin 4, connexin 43, microcephalin and nucleolin

Viral regulation of aquaporin 4, connexin 43, microcephalin and nucleolin

Predicting Risk and the Emergence of Schizophrenia

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

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