Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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) and latent inhibition (LI). The present study investigated in rats the effects of increasing or decreasing dopamine (DA) receptor activation within the medial prefrontal cortex (mPFC) by local administration of the indirect DA receptor agonist amphetamine (AMPH; 10.0 microg/side) or the DA antagonist cis-flupenthixol (FLU; 12.0 microg/side) on PPI and LI as well as on systemic AMPH-induced activity. The effects of intra-mPFC apomorphine (APO; 10.0 microg/side) on PPI were also tested. AMPH infusions decreased systemic AMPH-induced increase in locomotor activity in the open field, whereas FLU infusion was ineffective. Both infusions had no effect on LI and PPI. However, APO infusions induced a disruption of PPI. These results provide additional evidence that the mPFC is a component of the neural circuitry mediating PPI but plays no role in LI. In addition, they show that the behavioral outcomes produced by DA receptor activation/blockade in the mPFC of the rat cannot be explained by postulating a simple reciprocal relationship between the cortical and subcortical DA systems.
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PMID:Effects of local infusions of dopaminergic drugs into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine induced activity. 1062 35

The finding that influenza epidemics are associated with an increased risk of adult schizophrenia has been controversial. Data was obtained from Japan's governmental statistics, the Patient Survey. Index years were defined as 1957/1958, 1962, and 1965, and comparison years were defined 2 years before and 2 years after the index year. Subjects were patients with schizophrenia who were born in the index years of influenza epidemics. Periods 5 months after the influenza epidemics were defined as exposed months. Proportions of patients born during the exposed period in the index years were compared with those of patients born in the corresponding months in the comparison years. The proportions of patients born in the exposed months in the index years were not significantly different from those born in the corresponding months in the comparison years, with odds ratios around 1 in the whole country, the Kanto area, and the Shikoku/Kyushu area where a remarkable influenza epidemic was observed in 1957. No difference was observed in analyses stratified by sex. In Japan, there was no relationship between influenza epidemics and schizophrenic birth.
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PMID:No relationship between schizophrenic birth and influenza epidemics in Japan. 1075 55

Epidemiological evidence points to prenatal viral infection being responsible for some forms of schizophrenia and autism. We hypothesized that prenatal human influenza viral infection in day 9 pregnant mice may cause changes in the levels of neuronal nitric oxide synthase (nNOS), an important molecule involved in synaptogenesis and excitotoxicity, in neonatal brains. Brains from 35- and 56-day-old mice were prepared for SDS-gel electrophoresis and Western blotting using polyclonal anti nNOS antibody. Quantification of nNOS showed time and region-dependent changes in the levels of nNOS protein. Mean rostral brain area value from prenatally infected animals showed a significant (p=0.067) increase of 147% in nNOS levels at 35 days postnatally, with an eventual 29% decrease on day 56. Middle and caudal brain areas showed reductions in nNOS in experimental mice at 35 and 56 days, with a significant 27% decrease in nNOS in the middle segment of day 56 brains (p=0.016). Significant interactions were found between group membership and brain area (Wilks lambda=0.440, F(2.9)=5.72, p=0.025); there was also a significant interaction between brain area, group and age (Wilks lambda=0.437, F(2.9)=5.79, p=0.024). These results provide further support for the notion that prenatal viral infection affects brain development adversely via the pathological involvement of nNOS expression.
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PMID:Prenatal viral infection causes alterations in nNOS expression in developing mouse brains. 1084 64

Winter birth has been shown to increase the risk of schizophrenia in adult life. It has been hypothesized that this effect is due to seasonal variation in infectious diseases, including influenza, as exposure to influenza during mid gestation also increases the risk of schizophrenia. However, in many areas there is little variation in temperature during the year, although rainfall may vary greatly. We tested the hypothesis that, in a tropical region with wet and dry seasons, schizophrenia births would be related to rainfall. The data came from the city of Mossoro in north-eastern Brazil. In this area there is no meaningful variation in temperature, but there is a rainy season with little precipitation during the rest of the year. In this region, the prevalence of influenza parallels that of rainfall. There was a significant relationship between rainfall and the number of schizophrenia births three months later. In contrast, there was no significant relationship between rainfall and general population births three months later. The relationship of birth to rainfall, rather than winter birth, may be associated with risk of schizophrenia in tropical regions; exposure to influenza during gestation may be the basis for such a relationship.
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PMID:Schizophrenia and season of birth in a tropical region: relationship to rainfall. 1129 76

Recent evidence suggests that schizophrenia may result from a disruption of normal brain development during a critical, prenatal risk period in the 6th month of gestation. The phenotypic diagnostic manifestation of a basic genetic-neurodevelopmental disorder may consist of characteristics approximated by the DSM-IV diagnosis of "schizotypal personality disorder" (SPD). We identified male conscripts in Finland who, as fetuses, were exposed to the 1969 Hong Kong Influenza epidemic, along with a group of controls born during a relatively low year (1971) for infectious epidemics. It was hypothesized that among fetuses exposed to the influenza epidemic in their 6th month of gestation, we would observe an increased frequency of elevated (upper quartile) scores on a schizotypal personality characteristics (SPC) scale as compared to controls. A significantly higher proportion of the 6th month index exposed subjects (39%) had "elevated" SPC scale scores as compared to their controls (26%) (p<0.003). Further analyses revealed that these differences were accounted for by those exposed to the influenza epidemic in week 23 (51% vs. 24%) of the 6th month (p<0.005). Exploratory analyses for the other months did not reveal any significant differences. Implications and limitations of the week 23 findings are discussed.
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PMID:Adult schizotypal personality characteristics and prenatal influenza in a Finnish birth cohort. 1185 73

We review emerging evidence indicating that in utero exposure to infection is a risk factor for schizophrenia. It is hypothesized that a prenatal infection increases the liability to schizophrenia in adulthood by adversely affecting the maturation of critical brain structural and functional components implicated in the pathogenesis and pathophysiology of the disorder. Early evidence for a role of in utero infection includes investigations linking schizophrenia with birth during the winter and in urban regions, and ecologic studies demonstrating associations between influenza epidemics and births of pre-schizophrenic patients. The findings of the latter studies are, however, equivocal. To more rigorously address this question, our group has used increasingly sophisticated research designs that incorporate more refined measures of exposure and outcome, and continuous follow-up of treated cases. This work has already yielded several intriguing findings, including associations between schizophrenia and two in utero infections--rubella and respiratory infection. We also describe our ongoing birth cohort investigations that are expected to advance this work further, including studies that utilize maternal serum samples drawn during pregnancy of offspring who were later diagnosed with schizophrenia.
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PMID:In utero infection and adult schizophrenia. 1192 87

While genetic factors play a role in the etiology of schizophrenia, environmental factors contribute to the etiology of the disorder as well. If a woman is exposed during the second trimester of gestation to stressors such as the death of a loved one, influenza infection, or natural and man-made disasters, her baby has an increased risk of developing schizophrenia later in life. A common mechanism may mediate the effects of these diverse risk factors: a stress response during a restricted period of gestation may affect fetal brain development and, given the appropriate genetic predisposition, result in schizophrenia in adult life. Findings in animals exposed to prenatal stress strengthen the hypothesis that exposure to high glucocorticoid levels and/or other components of the stress response increases the risk of schizophrenia. These clinical and preclinical studies could be used to develop hypotheses that could then be tested in patients with schizophrenia.
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PMID:Glucocorticoid hormones and early brain development in schizophrenia. 1209 5

Epidemiological reports describe a strong association between prenatal human influenza viral infection and later development of schizophrenia. Postmodern human brain studies, however, indicate a lack of gliosis in schizophrenic brains presumably secondary to absence of glial cells during the second trimester viral infection in utero. We hypothesized that human influenza infection in day 9 pregnant mice would alter the expression of glial fibrillary acidic protein (GFAP, an important marker of gliosis, neuron migration, and reactive injury) in developing brains of postnatal days 0, 14 and 35 mice. Determination of cellular GFAP immunoreactivity (IR) expressed as cell density in cortex and hippocampus of control and experimental brains showed increases in GFAP-positive density in exposed cortical (P = 0.03 day 14 vs control) and hippocampal cells (P = 0.035 day 14, P = 0.034 day 35). Similarly, ependymal cell layer GFAP-IR cell counts showed increases with increasing brain age from day 0, to days 14 and 35 in infected groups (P = 0.037, day 14) vs controls. The GFAP-positive cells in prenatally exposed brains showed 'hypertrophy' and more stellate morphology. These results implicate a significant role of prenatal human influenza viral infection on subsequent gliosis, which persists throughout brain development in mice from birth to adolescence.
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PMID:Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice. 1214 Jul 87

A large body of research suggests a relationship between maternal influenza and the development of schizophrenia in the adult offspring. Some researchers, however, have questioned this association. A study by Crow and Done (1992) asserts that prenatal exposure to influenza does not cause schizophrenia. The methodology employed by Crow and Done may account for their null findings. Crow and colleagues assessed influenza by asking mothers at the time of birth to recall influenza infections experienced during pregnancy. Such retrospective recall may bias reporting. We assessed influenza symptoms during pregnancy in a group of 136 mothers at the twenty-fifth week of pregnancy, and again one or two days after birth. We compared accounts of influenza at the twenty-fifth week to recollection of influenza after birth. Results suggest that mothers tend to under-report infections when recalling infections after birth. Retrospective assessment of influenza symptoms at birth may be an inaccurate method of assessing influenza during pregnancy.
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PMID:Accuracy of retrospective reports of infections during pregnancy. 1245 22

Maternal viral infection is known to increase the risk for schizophrenia and autism in the offspring. Using this observation in an animal model, we find that respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring that display highly abnormal behavioral responses as adults. As in schizophrenia and autism, these offspring display deficits in prepulse inhibition (PPI) in the acoustic startle response. Compared with control mice, the infected mice also display striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs. Moreover, these mice are deficient in exploratory behavior in both open-field and novel-object tests, and they are deficient in social interaction. At least some of these behavioral changes likely are attributable to the maternal immune response itself. That is, maternal injection of the synthetic double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the offspring in the absence of virus. Therefore, maternal viral infection has a profound effect on the behavior of adult offspring, probably via an effect of the maternal immune response on the fetus.
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PMID:Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. 1251 27


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