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)

A non-randomized sample of patients suffering from attack-like schizophrenia and registered at the PND of 3 districts of Moscow served as materials for investigation. There were altogether 3576 persons. Patients living in the Proletarsky district were subjected to a catamnestic study. By the moment of examination they had suffered one attack. In view of the fact that the occurrence of the second attack obeys the law of exponential distribution, it was determined that the mono-attack course was recorded in 26.2% of all the registered patients with attack-like schizophrenia. It was shown that the proportion of patients with mono-attack schizophrenia increased with the disease standing. The data provide an opportunity of the probability forecasting of the disease stabilization after the first attack and can be used in the solution of the problems of the further disease course and registration of this patients, group.
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PMID:[Study of the incidence of single-attack course of schizophrenia based on epidemiological data]. 261 40

The following self-rating inventories were administered to 613 subjects (289 psychically ill patients and 324 healthy persons): The Basel Mood Inventory (BBI), the Freiburg Personality Inventory (FPI), the Giessen-Test (GT), the Complaint-List (HHM), and the Paranoid-Neuroticism-Depression-Scale (PND-S'). The main interest was put on examining the dimensionality of each inventory separately and all the inventories combined. The results are discussed with respect to the practical applicability. FPI and GT proved as two polyvalently applicable personality inventories (clinically as well as non-clinically) whose factorial structure is essentially verified. It was justified to eliminate "N" (neuroticism) from the PND in the newly revised version. Although "P" (paranoid) covers only a particular domain of paranoid tendencies the new test version (PD and PD') will be valuable in clinical use for group differentiation (a.o. for global diagnoses of depression and schizophrenia) in longitudinal as well as cross-sectional studies. The HHM covers mood state variables additionally, little differentiated though. The newer parallel forms suffer from the same deficiency. It could be confirmed that the BBI measures a particular mood-drive dimension and thus can be used independently or in combination with multidimensional personality inventories in longitudinal studies.
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PMID:[Self-evaluation questionnaires--factorial structure and indications for general practice]. 671 85

The neonatal (PND 7) lesion of the ventral hippocampus (VH) with ibotenic acid represents a well-established experimental paradigm that recapitulates many schizophrenia-like phenomena. In order to investigate molecular changes that could contribute to long lasting consequences on brain function, we have investigated the effects of the VH lesion on the expression for the trophic factors FGF-2 and BDNF. We used RNase protection assay to measure their mRNA levels in cortical regions of prepubertal (PND 35) and young adult (PND 56) animals, both under basal condition as well as in response to an acute restraint stress. The expression of BDNF was not altered by the VH lesion in prefrontal (PFC) and frontal cortex (FC) of PND 35 or PND 56 rats. An acute restraint stress at PND 35 produced a significant increase of the neurotrophin expression in PFC of sham as well as lesioned animals. However in young adult animals a significant elevation of BDNF expression was observed only in sham rats. We also found that the VH lesion produced a significant reduction of basal BDNF mRNA levels in the cingulate cortex of young adult, but not prepubertal rats. This effect was not accompanied by changes in the acute modulation of the neurotrophin, which was up-regulated by stress in both experimental groups. Conversely the expression of FGF-2 at PND 35 and PND 56 was not altered by early postnatal VH lesion, and there were no major differences between sham and lesioned animals in response to the acute stress. The changes in trophic factor expression may be relevant for the long-term effects of VH lesion on synaptic plasticity and may determine an increased vulnerability of the brain under challenging situations.
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PMID:Developmental and stress-related changes of neurotrophic factor gene expression in an animal model of schizophrenia. 1132 96

Perinatal cerebral hypoxia represents a major cause of obstetric complications and the resulting transient oxygen deficiency might belong to early risk factors for schizophrenia. The aim of this study was to evaluate possible long-term behavioral changes induced by one hour of continuous bilateral common carotid artery occlusion in 12-day-old male rats. Post-ischemic behavioral disturbances were evaluated in social (play) behavior on postnatal day 22 (PND 22), open field test (PND 35 and 50) and prepulse inhibition of the acoustic startle reflex (PND 50). Transient ischemia in neonatal rats was not significantly altered in social dyadic interactions evaluated in pre-weaning pups, but resulted in enhanced locomotor activity in pubertal rats (PND 35) and impaired prepulse inhibition of the startle reflex in post-pubertal males (PND 50). These behavioral alterations suggest that perinatal hypoxic/ischemic insults may represent a risk factor for later manifestation of specific features relevant to schizophrenia in predisposed individuals.
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PMID:Does neonatal brain ischemia induce schizophrenia-like behavior in young adult rats? 1708 6

Schizophrenia is a disorder of a neurodevelopmental origin manifested symptomatically after puberty. Structural neuroimaging studies show that neuroanatomical aberrations precede onset of symptoms, raising a question of whether schizophrenia can be prevented. Early treatment with atypical antipsychotics may reduce the risk of transition to psychosis, but it remains unknown whether neuroanatomical abnormalities can be prevented. We have recently shown, using in vivo structural magnetic resonance imaging, that treatment with the atypical antipsychotic clozapine during an asymptomatic period of adolescence prevents the emergence of schizophrenia-like brain structural abnormalities in adult rats exposed to prenatal immune challenge, in parallel to preventing behavioral abnormalities. Here we assessed the preventive efficacy of the atypical antipsychotic risperidone (RIS). Pregnant rats were injected on gestational day 15 with the viral mimic polyriboinosinic-polyribocytidylic acid (poly I:C) or saline. Their male offspring received daily RIS (0.045 or 1.2 mg/kg) or vehicle injection in peri-adolescence (postnatal days [PND] 34-47). Structural brain changes and behavior were assessed at adulthood (from PND 90). Adult offspring of poly I:C-treated dams exhibited hallmark structural abnormalities associated with schizophrenia, enlarged lateral ventricles and smaller hippocampus. Both of these abnormalities were absent in the offspring of poly I:C dams that received RIS at peri-adolescence. This was paralleled by prevention of schizophrenia-like behavioral abnormalities, attentional deficit, and hypersensitivity to amphetamine in these offspring. We conclude that pharmacological intervention during peri-adolescence can prevent the emergence of behavioral abnormalities and brain structural pathology resulting from in utero insult. Furthermore, highly selective 5HT(2A) receptor antagonists may be promising targets for psychosis prevention.
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PMID:Risperidone administered during asymptomatic period of adolescence prevents the emergence of brain structural pathology and behavioral abnormalities in an animal model of schizophrenia. 2043 20

Early maternal deprivation (MD) in rats (24h, PND 9-10) is a model for neurodevelopmental stress. Our previous data showed that MD altered the hippocampal levels of the endocannabinoid 2-AG and the expression of hippocampal cannabinoid receptors in 13-day-old rats, with males being more markedly affected. The aim of this study was to analyze the impact of MD on the enzymes involved in 2-AG biosynthesis (DAGLalpha and DAGLbeta) and degradation (MAGL) in relevant areas (DG, CA1, CA3) of the hippocampus in 13-day-old neonatal rats. The expression of the enzymes was evaluated by quantitative RT-PCR, immunohistochemistry, and densitometry. MD induced a significant increase in DAGLalpha immunoreactivity in both males and females, which was mainly associated with fibers in the polymorphic cell layer of the dentate gyrus and in the stratum pyramidale of CA3. In contrast, the molecular layer of the dentate gyrus showed a significant decrease in DAGLalpha immunoreactivity in MD males and females. No changes were observed in DAGLbeta immunoreactivity. MD induced a significant decrease in MAGL immunoreactivity in hippocampal CA3 and CA1 areas, more marked in males than in females, and that was mainly associated with fibers in all strata of CA3 and CA1. The results also showed a significant decrease of MAGL mRNA levels in MD males. These data support a clear association between neurodevelopmental stress and dysregulation of the endocannabinoid system. This association may be relevant for schizophrenia and other neurodevelopmental psychiatric disorders.
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PMID:Early maternal deprivation induces changes on the expression of 2-AG biosynthesis and degradation enzymes in neonatal rat hippocampus. 2059 24

Schizophrenia is a debilitating neurological disorder characterized by positive, negative, cognitive and/or emotional symptoms. Decreased social interaction is a common negative symptom. Social interaction can be readily observed in rats and is therefore an ideal target behaviour when evaluating an animal model of schizophrenia. The purpose of this study was to determine whether early alterations in glutamate signaling resulted in social withdrawal; a finding which would be consistent with existing animal models of schizophrenia and is observed within the clinical population. In the present study, male and female SD rat pups received daily injections (s.c.) of very low doses of the glutamate agonist domoic acid (DOM; 20 microg/kg) or saline during a critical period of CNS development (i.e., PND 8-14). As adults, rats were assessed for degree of social interaction. During testing, each test rat was placed in a social interaction arena and scored for social contact with and avoidance of, a same-sex untreated conspecific. No differences were found in overall activity, nor were differences present for time spent engaged in neutral behavior (i.e., not engaged in behaviour, either directed toward or in avoidance of, the stimulus rat). However, domoate-treated male rats demonstrated evidence of social withdrawal, as evidenced by a significantly greater amount of time spent in avoidance behaviour and a significantly less amount of time spent engaged in social contact. These findings are discussed in context of the significance of early alteration to glutamate signaling in the development of human neuropathological disorders.
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PMID:Altered social interaction in adult rats following neonatal treatment with domoic acid. 2110 56

Rats were treated postnatally (PND 5-16) with BSO (l-buthionine-(S,R)-sulfoximine) in an animal model of schizophrenia based on transient glutathione deficit. The BSO treated rats were impaired in patrolling a maze or a homing table when adult, yet demonstrated preserved escape learning, place discrimination and reversal in a water maze task [37]. In the present work, BSO rats' performance in the water maze was assessed in conditions controlling for the available visual cues. First, in a completely curtained environment with two salient controlled cues, BSO rats showed little accuracy compared to control rats. Secondly, pre-trained BSO rats were impaired in reaching the familiar spatial position when curtains partially occluded different portions of the room environment in successive sessions. The apparently preserved place learning in a classical water maze task thus appears to require the stability and the richness of visual landmarks from the surrounding environment. In other words, the accuracy of BSO rats in place and reversal learning is impaired in a minimal cue condition or when the visual panorama changes between trials. However, if the panorama remains rich and stable between trials, BSO rats are equally efficient in reaching a familiar position or in learning a new one. This suggests that the BSO accurate performance in the water maze does not satisfy all the criteria for a cognitive map based navigation on the integration of polymodal cues. It supports the general hypothesis of a binding deficit in BSO rats.
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PMID:Accurate performance of a rat model of schizophrenia in the water maze depends on visual cue availability and stability: a distortion in cognitive mapping abilities? 2154 61

Animal models have greatly contributed to the understanding of neuropsychiatric disorders and have provided extensive evidence for the "neurodevelopmental hypothesis." In this regard, a single and prolonged episode (24 h) of early maternal deprivation early in life, on postnatal day 9, has been proposed as an animal model for the investigation of certain neuropsychiatric disorders, including schizophrenia. Since metabolic changes in hippocampus (HIP) and prefrontal cortex (PFC) have been described among schizophrenic patients by using ex vivo high-resolution magic angle spinning (HR-MAS) proton ((1)H) nuclear magnetic resonance spectroscopy, in the present study we aimed to investigate the effects of maternal deprivation (MD) on the metabolite profiles of the developing brain by using the HR-MAS technique. MD significantly altered the hippocampal and cortical metabolic profile of neonatal rats (PND 13) in a sex-dependent manner. Glutamine and glutamate (Glx) and taurine of male and female rat pups were altered in both brain areas analyzed. Differences in hippocampal phosphorylethanolamine have also been found as a function of the MD protocol. In addition, MD induced some other region- and sex-dependent effects, including changes in N-acetyl aspartate and total choline signals in the hippocampi of male pups. Present findings indicate a different brain metabolic profile in our animal model of early life stress suggesting its potential utility in the implementation of translational neuropsychiatric research.
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PMID:Analyzing the effects of a single episode of neonatal maternal deprivation on metabolite profiles in rat brain: a proton nuclear magnetic resonance spectroscopy study. 2212 Apr 35

Although several findings indicate an association between adolescent cannabis abuse and the risk to develop schizophrenia later in life, the evidence for a causal relationship is still inconclusive. In the present study, we investigated the emergence of psychotic-like behavior in adult female rats chronically exposed to delta-9-tetrahydrocannabinol (THC) during adolescence. To this aim, female Sprague-Dawley rats were treated with THC during adolescence (PND 35-45) and, in adulthood (PND 75), a series of behavioral tests and biochemical assays were performed in order to investigate the long-term effects of adolescent THC exposure. Adolescent THC pretreatment leads to long-term behavioral alterations, characterized by recognition memory deficits, social withdrawal, altered emotional reactivity and sensitization to the locomotor activating effects of acute PCP. Moreover, since cortical disinhibition seems to be a key feature of many different animal models of schizophrenia and GABAergic hypofunction in the prefrontal cortex (PFC) has been observed in postmortem brains from schizophrenic patients, we then investigated the long-lasting consequences of adolescent THC exposure on GABAergic transmission in the adult rat PFC. Biochemical analyses revealed that adolescent THC exposure results in reduced GAD67 and basal GABA levels within the adult PFC. GAD67 expression is reduced both in parvalbumin (PV)- and cholecystokinin (CCK)-containing interneurons; this alteration may be related to the altered emotional reactivity triggered by adolescent THC, as silencing PFC GAD67 expression through a siRNA-mediated approach is sufficient to impact rats' behavior in the forced swim test. Finally, the cellular underpinnings of the observed sensitized response to acute PCP in adult THC-treated rats could be ascribed to the increased cFos immunoreactivity and glutamate levels in the PFC and dorsal striatum. The present findings support the hypothesis that adolescent THC exposure may represent a risk factor for the development of a complex psychotic-like behavior in adulthood.
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PMID:Alterations of prefrontal cortex GABAergic transmission in the complex psychotic-like phenotype induced by adolescent delta-9-tetrahydrocannabinol exposure in rats. 2420 Aug 67


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