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)

We have previously reported that, from a phenomenological standpoint, the behavioral manifestations of cats chronically intoxicated with amphetamine parallel the evolution of the paranoid psychosis induced by the drug in humans. However, certain manifestations in the cat, such as frozen postures, disjunctive behaviors and postures, cataleptic-like phenomena, obstinate progression, loss of righting reflex and pupillary changes, did not appear to be consistent with the phenomenology of the paranoid psychosis. Since treatment of schizophrenic patients with disulfiram, an inhibitor of norepinephrine synthesis that acts at the level of the enzyme dopamine beta-hydroxylase, thereby leading to increased dopamine concentrations, had been found to profoundly exaggerate psychotic symptomatology, amphetamine behavioral syndrome in the cat as it is modified by pretreatment with disulfiram. Following such pretreatment, a faster development of certain end-stage components of the amphetamine syndrome was obtained. Thus, on the first day, development of a Reactive attitude and of more prominent behavioral disjunction occurred with the combined drug administration as compared with amphetamine alone. In contrast with the facilitation of these behaviors was the absence of dyskinesias and hyperreflexia on that day. Stereotyped behavior, loss of motor initiative and hyperkinetic activity were markedly enhanced and appeared with a shorter latency period on subsequent days of the intoxication cycle. Loss of righting reflex was an early manifestation in these animals. During the later days, the particularly high level of compulsive activity was evident from the occurrence of an obstinate progression syndrome and the performance of stereotyped movements of the head in the presence of a crucifixion posture. In general, modification of the amphetamine effects on behavior was in a direction consistent with comparable features in experimental catatonia and the catatonic form of schizophrenia. The need to integrate such phenomena in any amphetamine model of psychosis is stressed and analogies are drawn with similar features reported in animals treated with bulbocapnine or other psychotogenic compounds and with symptoms of human amphetamine psychosis and schizophrenia.
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PMID:Effects of disulfiram on the amphetamine-induced behavioral syndrome in the cat as a model of psychosis. 124 12

MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo-(a,d)cyclohepten-5,10-imi ne hydrogen maleate], which blocks glutamatergic transmission at the NMDA-receptor-gated ion channel, induced stereotypies which are similar to those found after intrastriatal injections of AP-5, e.g. sniffing and locomotion. Tests in familiar or unfamiliar environment (non-stressful or stressful situation) did not qualitatively change MK-801-induced effects. Haloperidol (0.1 mg/kg, IP) delayed the onset and shortened the duration of MK-801 (0.16; 0.33 mg/kg, IP)-induced stereotypy whereas clozapine (5 mg/kg, SC) potently antagonized it. However, exact quantification of sniffing, measured in an experimental chamber designed for this purpose, revealed an antagonism by both drugs, haloperidol as well as clozapine. Stereotypy is considered to represent an animal model of schizophrenia, and the antagonism of stereotypy with classical (haloperidol) as well as with atypical (clozapine) antipsychotic drugs is in accordance with the glutamate hypothesis of schizophrenia.
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PMID:MK-801-induced stereotypy and its antagonism by neuroleptic drugs. 197 47

Twenty-five closed-head-injured adults (24 males, 1 female; M age = 28.8 years) were classified as "recovered" if they had returned to work, school, or a sheltered workshop for which pay was received and "non-recovered" if they did not meet these criteria. Current status was compared with MMPI, Adaptive Behavior Scale (ABS), and "Quality of Life" Rating Scale (QLRS) scores at time of entry into a rehabilitation program. The "non-recovered" group was significantly higher on the PD (Psychopathic deviate) scale. No differences were found between groups on the Sc (Schizophrenia) or K (Validity) scales. The "recovered" group was significantly higher on the ABS Economic Activity domain and significantly lower in the Violent & Destructive, Antisocial, Rebelliousness, Untrustworthiness, Stereotyped Behavior & Odd Mannerisms, and Psychological Disturbance behavior domains. The self-ratings (QLRS) of the "nonrecovered" subjects were significantly more distinct from the ratings made by their relatives or significant others than were those of the "recovered" subjects.
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PMID:Prediction of recovery for closed-head-injured adults: an evaluation of the MMPI, the Adaptive Behavior Scale, and a "Quality of Life" Rating Scale. 369 60

The ability of phencyclidine (PCP) to model schizophreniform psychosis is believed to be related to its ability to produce both hypoglutamatergia and hyperdopaminergia. As such, identification of PCP-stimulated behaviors may be important for the development of animal models of schizophrenia. In this study, MK-801 [(+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cycloheptane-5,10-imine maleate], a high-affinity PCP analogue, was administered to mice in order to stimulate "PCP behaviors." These PCP behaviors were compared with behaviors stimulated by apomorphine, a dopamine agonist. Stereotyped behavior was assessed by both visual observations and automated measurements. Visual observations showed highly intense gnawing and sniffing in apomorphine-treated mice and the absence of gnawing in MK-801-treated mice. Automated stereotypic measures showed that, compared with vehicle-treated controls, there were frequent dissociations between MK-801 and apomorphine. Conceivably, a compound that attenuates PCP-stimulated behaviors while sparing apomorphine-stimulated behaviors would possess both antipsychotic efficacy and be devoid of undesirable side effects associated with dopamine blockade.
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PMID:Differentiation between MK-801- and apomorphine-induced stereotyped behaviors in mice. 850 39

Adults with predominantly severe and profound mental retardation (N = 180) who lived in a developmental center were assessed with the Behavior Problems Inventory and the Diagnostic Assessment for the Severely Handicapped-II. Individuals with self-injurious, stereotyped, or aggressive/destructive behavior had generally higher psychopathology scores than individuals without, and the presence of behavior problems increased the likelihood of almost all psychiatric conditions up to three-fold. Factor analysis revealed that behavior problems tended to be associated with psychiatric conditions conventionally linked with behavior problems. A Self-Injury and Aggression/Destruction factor was related to impulse control and conduct problems, and a Stereotyped Behavior factor was linked to pervasive developmental disabilities and somewhat less so to schizophrenia. Stereotyped Behavior factor was independent of the Self-Injury/Aggression/Destruction factor.
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PMID:Relationships between psychiatric conditions and behavior problems among adults with mental retardation. 1465 52

Stereotyped behavior and left-sided orientation biases, associated with the dopamine (DA) system, were observed in populations of the schizophrenia spectrum disorders. We investigated whether heightened DA concentrations influence both side biases and stereotyped responding in a visuo-motor computer task, in which 90, 180, and 270 degrees rotated objects had to be brought into a target position. To account for the role of the schizophrenia spectrum, task performance was also analyzed as a function of healthy participants' high or low magical ideation (MI), a positive schizotypal feature. The first 36 participants (20 women) remained substance free. In a second sample, 20 men received levodopa and 20 men a placebo in a double-blind procedure. Results showed that high MI scorers responded more stereotyped than low MI scorers, without being specifically biased towards the left side. Rotation preferences toward one or the other side made high MI scorers less flexible for objects efficiently to be rotated into the opposite direction. This inflexibility may reflect impaired left hemisphere functioning. Unexpectedly, in the levodopa group, high MI scorers performed superior to low MI scorers. Since DA actions appear to follow an inverted U-shape function, the 'low' performing high MI scorers profited from the enhanced DA availability. Our observation in the levodopa group points to a dissociation between schizotypy and schizophrenia: while cognitive improvement in schizophrenia can occur after treatment with atypical neuroleptic agents, in our positive schizotypal participants a DA agonist resulted in improved task performance. This dissociation may point to protective neurochemical mechanisms preventing healthy schizotypes from developing full-blown psychotic symptoms.
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PMID:Nonstereotyped responding in positive schizotypy after a single dose of levodopa. 1517 45

Motor abnormalities represent a neurobehavioral domain of signs intrinsic to schizophrenia-spectrum disorders, though they are commonly attributed to medication side effects and remain understudied. Individuals with first-episode psychosis represent an ideal group to study innate movement disorders due to minimal prior antipsychotic exposure. We measured dyskinesias, stereotypies, and catatonic-like signs and examined their associations with: (1) age at onset of psychotic symptoms and duration of untreated psychosis; (2) positive, negative, and disorganized symptoms; (3) neurocognition; and (4) neurological soft signs. Among 47 predominantly African American first-episode psychosis patients in a public-sector hospital, the presence and severity of dyskinesias, stereotypies, and catatonic-like features were assessed using approximately 30-min video recordings. Movement abnormalities were rated utilizing three scales (Dyskinesia Identification System Condensed User Scale, Stereotypy Checklist, and Catatonia Rating Scale). Correlational analyses were conducted. Scores for each of three movement abnormality types were modestly inter-correlated (r=0.29-0.40). Stereotypy score was significantly associated with age at onset of psychotic symptoms (r=0.32) and positive symptom severity scores (r=0.29-0.41). There were no meaningful or consistent associations with negative symptom severity, neurocognition, or neurological soft signs. Abnormal movements appear to represent a relatively distinct phenotypic domain deserving of further research.
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PMID:Abnormal movements in first-episode, nonaffective psychosis: dyskinesias, stereotypies, and catatonic-like signs. 2561 34

Chemokines play important roles in the central nervous system, including mediating neuroinflammation and guiding the intracortical migration of interneurons during development. Alteration in parvalbumin-positive interneurons is a key neuropathological hallmark of multiple mental conditions. We recently reported a significant reduction in the expression of CXCL12 in olfactory neurons from sporadic cases with schizophrenia compared with matched controls, suggesting a role for CXCR4/CXCL12 signaling in mental conditions. Thus, we depleted the chemokine receptor Cxcr4 from mice using the parvalbumin-2A-Cre line. The conditional knockout mice exhibited a unique behavioral phenotype involving increased stereotypy. Stereotypy is observed in many psychiatric conditions, including schizophrenia, autism, and dementia. Thus, the Cxcr4 conditional knockout mice may serve as a model for this symptomatic feature.
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PMID:Increased stereotypy in conditional Cxcr4 knockout mice. 2645 29

Objective: High lipophilicity and extensive hepatic metabolism limits the oral application of risperidone in the treatment of CNS disorders. In order address this limitation, risperidone (RS) loaded chitosan nanoparticles (CS-NPs) were processed for intranasal administration in the management of schizophrenia. Methods: RS loaded CS-NPs were prepared by ionic gelation of chitosan with tripolyphosphate and stabilized by tween 80/ poloxamer 188. The CS-NPs were characterized by FTIR, DSC, particle size, zeta potential and surface morphology. Entrapment efficiency, mucoadhesive strength, in vitro drug release, and release kinetics of CS-NPs were evaluated. Pharmacokinetics and pharmacodynamics of RS loaded CS-NPs were studied using Wistar rats. Stereotypy behavior and swimming normalization tests were conducted in amphetamine induced psychosis in animals. Results: Risperidone nanoparticles (RP12) were produced with an average size of 86 nm, polydispersity index of 0.287, zeta potential of +36.6 mV, mucoadhesion of 68.9% and entrapment efficiency of 77.96%. CS-NPs released the RS in controlled manner with Fickian diffusion mode. Maximum concentration of RS in plasma was 1240 ng/ml at 4 h for RP12, and 403.8 ng/ml at 2 h for RS sample. RS loaded CS-NPs significantly reduced the stereotypy score in experimental animals that indicated the efficiency of CS-NPs in delivery of RS at brain tissues and moreover amphetamine effect was reversed. Thus, RS loaded CS-NPs proved as potential delivery systems against induced psychotic disorders. Conclusion: Risperidone loaded chitosan nanoparticles were effective against schizophrenia via intranasal route.
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PMID:Formulation and biopharmaceutical evaluation of risperidone-loaded chitosan nanoparticles for intranasal delivery. 3109 71