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)

Post-mortem brain tissue was obtained from 28 patients with brain disorders, of which 15 had clinically diagnosed schizophrenia, 6 Alzheimer type dementia, 5 dementia with tangles and 2 cases of Down's syndrome. The controls were 22 cases from autopsies without brain disorders or with no known episodes of brain disorder. The tissues were stained for the detection of carbohydrate deposits in the hippocampal formation, using lectin, immunohistochemical and conventional staining methods. The staining revealed the existence of spherical deposits in the inner and middle molecular layers of the dentate gyrus in the hippocampal formation which contained fucose, galactose, N-acetyl galactosamine, N-acetyl glucosamine, sialic acid, mannose and chondroitin sulfate. The number of the deposits was higher in patients with brain disorder such as schizophrenia, Alzheimer type dementia, dementia with tangles or Down's syndrome, and in some aged individuals, in comparison to those in younger individuals. No deposits were detected in a few younger or aged individuals. Spherical deposits 3-10 microm in diameter may be an immature form of the corpora amylacea, since they were similar in the histochemical characteristics with lectin, immunohistochemical and conventional staining methods. However, differing staining ability by hematoxylin, periodic acid Schiff's reagent and antibodies against the intracellular degraded proteins such as ubiquitin and tau-protein was observed. The antibodies against ubiquitin and tau-protein showed clear reactivity with the corpora amylacea and no reactivity with spherical deposits, indicating that the corpora amylacea has an intracellular origin and spherical deposits an extracellular matrix origin. The results obtained in this study indicate that not only neuronal degeneration but also unusual glycometabolism in neurons may disturb the neuronal function and cause brain disorders, and that spherical deposits may cause dysfunction of the neuronal network in the dentate gyrus of the hippocampus which is closely linked with recognition and memory functions.
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PMID:The carbohydrate deposits detected by histochemical methods in the molecular layer of the dentate gyrus in the hippocampal formation of patients with schizophrenia, Down's syndrome and dementia, and aged person. 1144 83

The functions and interactions of cortical and subcortical dopamine systems are of interest because alterations in these systems have been implicated in neuropsychiatric diseases, such as schizophrenia. It has been proposed that prefrontal dopamine transmission may oppose dopamine transmission in subcortical sites, such as the nucleus accumbens. Accordingly, reduced prefrontal dopamine transmission would be expected to enhance or induce behavioral effects that have been associated with stimulation of accumbal dopamine receptors. In rats, spontaneous and amphetamine-induced activity is supported by dopamine receptor stimulation in the nucleus accumbens, while prepulse inhibition (PPI) of the acoustic startle response, which is used to measure sensorimotor gating and is disrupted in schizophrenia, is reduced by increased accumbal dopamine receptor stimulation. In the present experiments, we found that bilateral infusion of the dopamine D1/D2 receptor antagonist cis-flupenthixol dihydrochloride into the medial prefrontal cortex of Wistar rats (25 microg each side) reduced spontaneous activity and completely blocked induction of hyperactivity by systemic administration of D-amphetamine sulfate (1 mg/kg), while not affecting PPI. These findings do not support an antagonism between prefrontal and accumbal dopamine in the control of behavior. Rather, our data demonstrate that prefrontal dopamine transmission may modulate some behavioral processes in a similar way to accumbal dopamine.
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PMID:Dopamine receptor blockade in the rat medial prefrontal cortex reduces spontaneous and amphetamine-induced activity and does not affect prepulse inhibition. 1247 19

Changes in locomotor and stereotypic activities induced by an i.p. injection of either (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cycloheptan-5,10-imine maleate (dizocilpine or MK-801; 0.3 mg/kg) or D-amphetamine sulfate (AMPH; 1.5 mg/kg) were studied in male Mill Hill hooded rats of different age. The following age groups of animals were considered: 28-30 postnatal day (PND)-old rats (peripubertal), 48-50 PND-old (pubertal), 3-month-old (adults), 12-month-old (middle-aged) and 24-month-old (aged). The motor response was measured by an automated animal activity measuring system. The obtained results showed that: (1) in contrast to AMPH, MK-801 induced more pronounced increases of both locomotor and stereotypic activities in peripubertal and pubertal than in adult and aged rats; (2) AMPH induced the same locomotor and stereotypic activity increase in pubertal, adult and middle-aged rats; (3) both AMPH and MK-801 led to a senescence-related decrease of motor activity. These data suggest that the balance of the glutamatergic and dopaminergic systems changes during aging. Such a change is important in understanding schizophrenia and the motor system decline observed in the later stages of life.
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PMID:Age-related differences in MK-801- and amphetamine-induced locomotor and stereotypic activities of rats. 1288 79

It has recently been suggested that sigma receptors are involved in psychiatric disorders. Sigma 1 receptor antagonists are effective in animal models of positive symptoms, cognitive deficit and disruption of prepulse inhibition in schizophrenia. They also inhibit the development and expression of the conditioned place preference induced by cocaine. On the other hand, sigma 1 receptor agonists reduce the immobility time in the forced swimming and tail suspension tests. Furthermore, sigma 1 receptor agonists attenuate the conditioned fear stress (CFS) response (which is not attenuated by typical anxiolytics or antidepressants) in rodents. The attenuating effects are mediated through sigma 1 receptors, which are closely related to the mesolimbic dopaminergic systems. Sigma 1 receptor agonists also have anti-amnesic effects in various experimental models. Neurosteroids such as dehydroepiandrosterone sulfate and pregnenolone sulfate attenuate the CFS response and have anti-amnesic effects, the effects being mediated via sigma 1 receptors. These findings suggest that sigma receptors are novel potential targets for the treatment of psychiatric disorders such as schizophrenia, drug abuse, depression and dementia.
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PMID:[Effects of sigma receptor ligands on psychiatric disorders]. 1465 24

Dehydroepiandrosterone (DHEA) and its sulfate derivative DHEA-S are neurosteroids, produced in the brain, and neuroactive steroids, produced in the adrenals and affecting the brain. We compared the ratios of serum cortisol/DHEA or DHEA-S in schizophrenia patients with normal subjects, and determined the correlation of these ratios with psychopathology and distress. Early morning plasma concentrations of DHEA, DHEA-S, and cortisol were determined by radioimmunassay in 40 medicated schizophrenia inpatients, and 15 healthy subjects with similar age and sex distribution. Subjects were assessed for psychopathology using the Positive and Negative Syndrome Scale (PANSS) and the Montgomery and Asberg Depression Rating Scale (MADRS), anxiety, anger, emotional and somatic distress levels. Schizophrenia inpatients demonstrated significantly higher levels of state and trait anxiety, anger expression index, emotional and somatic self-reported distress scores. Cortisol/DHEA and cortisol/DHEA-S ratios were significantly higher in schizophrenia patients than in healthy comparison subjects. Both ratios correlated positively with age and duration of illness; cortisol/DHEA-S ratio also showed positive association with age of illness onset. When age, illness duration and age of onset were controlled, cortisol/DHEA-S ratio significantly correlated with severity of depression (MADRS, r=0.33, p=0.048), state and trait anxiety (r=0.43, p=0.008 and r=0.40, p=0.014, respectively), trait anger (r=0.41, p=0.012), angry temperament (r=0.46, p=0.004), anger expression index (r=0.36, p=0.033), and hostility (r=0.42, p=0.010). No significant association was found between these ratios and severity of psychopathology, and type or dosage of antipsychotic agents. Thus, elevated cortisol/DHEA and/or cortisol/DHEA-S ratios in schizophrenia patients are positively associated with higher scores for anxiety and anger, depression and hostility, age and age of onset/duration of illness, but are independent of severity of psychopathology (PANSS) and antipsychotic treatment.
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PMID:Elevation of the cortisol/dehydroepiandrosterone ratio in schizophrenia patients. 1516 35

The administration of psychostimulants to children with psychotic symptoms is controversial. This study reports the stimulant drug response of 5 children, aged 8-15 years, with childhood-onset schizophrenia (COS) and comorbid attention deficit hyperactivity disorder (ADHD). Four COS inpatients were given stimulants for comorbid ADHD after stabilization of psychosis on antipsychotic medication. A fifth COS inpatient received stimulants while still actively psychotic, despite concurrent neuroleptic treatment. Data from the 10-item Brief Conners Teachers Ratings Scale (BCTRS) were examined the week before, and the week after, stimulant addition. A paired t test, conducted using Conners Teachers data from these 4 subjects, indicated significant improvement in ADHD symptoms (p = 0.02). Data obtained from a retrospective chart review indicated no significant worsening of psychosis. The 2 subjects treated with mixed salts of dextroamphetamine sulfate and amphetamine sulfate remained on that medication at 6 months and at the 2-year follow-up. Our results suggest that ADHD comorbid with COS may be safely treated with a stimulant, once the psychosis is stabilized. A systematic investigation of this question may be warranted.
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PMID:Stimulant drug treatment in childhood-onset schizophrenia with comorbid ADHD: an open-label case series. 1565 May 2

Neurosteroids, such as dehydroepiandrosterone (DHEA) and DHEA-sulfate (the most abundant steroid in the body), regulate neuronal functions by influencing neuronal excitability. Prominent effects are exerted on the gamma-aminobutyric (GABA) receptors. DHEA has demonstrated efficacy in improvement of mood in humans, especially in middle-aged and elderly individuals. In the author's study, administering DHEA to patients with schizophrenia who had moderate to severe negative symptoms and who were maintained on antipsychotic medications induced significant improvement, more so in women and corresponding to increased plasma levels of DHEA and DHEA-S. Possible mechanisms of action include enhanced dopamine release, enhanced responsiveness at the N-methyl D-aspartate (NMDA) receptor, facilitation of sigma receptor activity, selective potentiation of dopaminergic neurotransmission, and a general anxiolytic action. Side effects are reviewed, and the currently experimental status of DHEA augmentation is emphasized.
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PMID:Dehydroepiandrosterone (DHEA) augmentation in the management of schizophrenia symptomatology. 1586 21

Dehydroepiandrosterone (DHEA) or their sulfate conjugate (DHEAS) (together abbreviated DHEA(S)) exert multiple effects in the central nervous system, and may be involved in the pathophysiological processes in schizophrenia. This prospective study aimed to investigate whether serum cortisol/DHEA(S) molar ratios are associated with response to antipsychotic treatment during the exacerbation of schizophrenia. Serum DHEA(S) and cortisol were determined at baseline, and 2 and 4 weeks later for 43 medicated schizophrenia inpatients with acute exacerbation. The patients were treated with stable doses of antipsychotic agents up to 2 weeks prior to entering the study and for the 4-week duration of the study after which they were classified as either responders or nonresponders to treatment. Findings suggest that responders had significantly higher serum cortisol levels and cortisol/DHEA(S) ratios compared with nonresponders. These differences remained significant at three time points controlling for gender, age, severity of symptoms and emotional distress, benzodiazepines, type or dosage of antipsychotic agents, and background variables. The logistic regression model shows advantages of both cortisol/DHEA(S) molar ratios vs serum cortisol and DHEA(S) concentrations for prediction of responsivity to antipsychotic treatment. No significant canonical correlations were observed between changes from baseline through end-of-study in hormonal values and severity of symptoms and emotional distress among responders and nonresponders. Thus, these data provide evidence that elevated serum cortisol and cortisol/DHEA(S) ratios may serve as markers of biological mechanisms that are involved in responsivity of schizophrenia patients to antipsychotic treatment.
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PMID:Cortisol/dehydroepiandrosterone ratio and responses to antipsychotic treatment in schizophrenia. 1587 Aug 35

This study was undertaken to examine the effects of the selective serotonin reuptake inhibitors fluvoxamine and paroxetine on cognitive deficits in mice after repeated administration of the N-methyl-D-aspartate receptor antagonist phencyclidine (PCP). In the novel object recognition test, repeated administration of PCP (10 mg/kg/day, 10 days) significantly decreased the exploratory preference in the retention test session, but not in the training test session. PCP-induced cognitive deficits were significantly improved by subsequent subchronic (2-week) administration of fluvoxamine (20 mg/kg/day), but not paroxetine (10 mg/kg/day). Furthermore, the effect of fluvoxamine on PCP-induced cognitive deficits was antagonized by co-administration of the selective sigma-1 receptor antagonist NE-100 (1 mg/kg/day). Moreover, PCP-induced cognitive deficits were also significantly improved by subsequent subchronic (2-week) administration of the selective sigma-1 receptor agonist SA4503 (1 mg/kg/day) or neurosteroid dehydroepiandrosterone 3-sulfate (DHEA-S; 25 mg/kg/day). The effects of SA4503 or DHEA-S were also antagonized by co-administration of NE-100 (1 mg/kg/day), suggesting the role of sigma-1 receptors in the active mechanisms of these drugs. In contrast, acute single administration of these drugs (fluvoxamine, paroxetine, SA4503) alone or combination with NE-100 did not alter PCP-induced cognitive deficits. The present study suggests that agonistic activity of fluvoxamine at sigma-1 receptors plays a role in the active mechanisms of fluvoxamine on PCP-induced cognitive deficits in mice. Therefore, sigma-1 receptor agonists such as fluvoxamine would be potential therapeutic drugs for the treatment of the cognitive deficits of schizophrenia.
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PMID:Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of fluvoxamine: role of sigma-1 receptors. 1649 35

The cyclic adenosine monophosphate-specific phosphodiesterase-4 (PDE4) gene family is the target of several potential therapeutic inhibitors and the PDE4B gene has been associated with schizophrenia and depression. Little, however, is known of any connection between this gene family and autism, with limited effective treatment being available for autism. We measured the expression of PDE4A and PDE4B by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting in Brodmann's area 40 (BA40, parietal cortex), BA9 (superior frontal cortex), and cerebellum from subjects with autism and matched controls. We observed a lower expression of PDE4A5, PDE4B1, PDE4B3, PDE4B4, and PDE4B2 in the cerebella of subjects with autism when compared with matched controls. In BA9, we observed the opposite: a higher expression of PDE4AX, PDE4A1, and PDE4B2 in subjects with autism. No changes were observed in BA40. Our results demonstrate altered expressions of the PDE4A and PDE4B proteins in the brains of subjects with autism and might provide new therapeutic avenues for the treatment of this debilitating disorder.
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PMID:Expression of phosphodiesterase 4 is altered in the brains of subjects with autism. 1809 Mar 23


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