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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some of the difficulties of trying to establish an animal model of schizophrenia are first considered. Then, after a review of the evidence on the experimental psychopathology of schizophrenia, particularly that concerned with attention and arousal, it is concluded that the core feature which needs to be modeled in animals is some aspect of "input dysfunction." It is argued that, of the pharmacological strategies, LSD-25 comes nearest to meeting that requirement, for two reasons. First, the phenomenology of an LSD "model psychosis" closely parallels that of the natural disease. Secondly, the experimental effects of the drug, both in animals and man, are very similar to or can be closely aligned theoretically with those of schizophrenia. An example is quoted from work in the author's laboratory where LSD was found to produce psychophysiological effects virtually identical to those observed occurring naturally in acute psychotic patients and in normal subjects high in "psychotic" personality traits. It is suggested that the rejection of LSD as a drug model was premature, especially as the currently popular preference for amphetamine has not been vindicated, either by the latter's ability to mimic an important central feature of the psychotic state or by work on dopamine as a specific common mediator of amphetamine psychosis and of schizophrenia.
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PMID:Animal models of schizophrenia: the case for LSD-25. 74 71

In a series of 103 psychotic patients with evidence of drug abuse, the following facts came to light. 1. A definitive diagnosis was made in 94%. In 6% of these cases the diagnosis remained unclear even after having been admitted for a second time. 2. Seventy-four percent (72 of 97) of the patients, who abused various drugs, usually in combination had organic psychoses, and 26% (25 of 97) were diagnosed as schizophrenics. 3. Of 36 patients, who suffered psychotic episodes due to the abuse of cannabis, or LSD, or heroin, 21 (= 58%) were schizophrenics. 4. In those cases showing organic psychoses, thought insertion, thought withdrawal, and thought broadcasting were not found. However all other first- (and second-) rank symptoms (Kurt Schneider) of schizophrenia were found. Perhaps this might be of help as a differential criterion. 5. The fact of drug abuse at the outset of a schizophrenia is dependent on the schizophrenic symptomatology. The use of and attitude to the drug as well as the experiencing of the drug's effects changes in the further course of the psychosis. This last point might also be of value in the differential diagnosis.
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PMID:[Drug abuse and schizophrenia (author's transl)]. 99 96

Acute and chronic psychotic states in juvenile drug addicts demand careful observation of syndrome-genetic and differential diagnostic factors. Not only the diagnosis of a schizophrenic or affective juvenile psychosis and their differentiation from phase-specific developmental crises may often be difficult. A further problematic field are special aspects of symptomatic psychoses and particularly states due to drug addiction with hashish, LSD and amphetamines and the effect of drugs on already existing endogenous psychoses. This demands subtile phenomenologic description and syndrome-genetic assessment. One will have to take into account the complexity of drug effects and whether a psychosis existed already before addiction, whether drugs have provoked a latent psychosis, whether a purely symptomatic psychosis mimics a schizophrenia or whether irreversible personality changes with secondary psychotic behavior have developed.
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PMID:[Differential diagnosis and syndrome-genetic problems and aspects of drug-induced psychoses in juveniles (author's transl)]. 105 11

This paper presents the psychodynamic investigation of a case of schizophrenia, which developed on the basis of a LSD-psychosis. It is a contribution to a treatment of schizophrenia, in which the coexistence of biological and psychological factors is taken into consideration. Biological premises do not invalidate the psychological understanding of many symptoms. Psychodynamic experience permits the psychiatrist to encounter the patient adaquately, even if the possibility for a long psychotherapeutic treatment is absent.
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PMID:[Delusion and understanding (author's transl)]. 112 26

The effects of LSD are characterized by a number of disturbances of perception and experience, which can be observed in the fields of visual, spatial and temporal perception and of affectivity. We also see disturbances of experience, which can otherwise be observed only in psychoses, for example reduction or change of cognitive functions, but also depersonalization and euphoria. In atypical courses of intoxication ("horror-trips") anxiety and excitement are predominant. Atypical courses of intoxication may be interrupted by "talk down" and additional application of tranquilizers. In a certain number of LSD-users in our clinic we saw psychoses. We classify them into flash-backs, exogenic (toxic) psychoses and so-called "endoform psychoses". The latter implies three possible constellations: accidental coincidence of LSD-use and psychosis; pre-existing psychosis with symptomatic use of LSD as an attempt of self-treatment; finally the onset of a psychosis may be triggered by the use of the halluzinogen. From the symptomatological cross-section they cannot reliably be distinguished from real schizophrenia. An independent nosological unit "LSD-psychosis" does not seem to exist.
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PMID:[Problems of toxic psychosis as illustrated on the example of the so-called LSD psychosis]. 119 15

Shortly after the introduction of the first neuroleptics a serotonin hypothesis of schizophrenia has been proposed. But neuroleptics in animals and in man were found to produce effects more consistently related to inhibition of the dopaminergic than of any other type of neurotransmission. However, two early neuroleptics, pipamperone and clozapine, act pharmacologically more on 5-HT2 than on D2 receptors. Both have a distinct clinical profile and low EPS liability. The development of selective 5-HT2-antagonists, devoid of LSD-like properties, resulted in a first compound, ritanserin. Clinically, the highly specific 5-HT2-antagonism of ritanserin improves dysthymia, increases slow wave sleep and supports classical neuroleptic treatment by decreasing negative symptoms and EPS. These properties, being valuable by themselves, have been associated to dopamine D2-antagonism in the new antipsychotic risperidone, which is an extremely potent 5-HT2-antagonist. At doses of 5 mg daily risperidone acts on both negative and positive symptoms of schizophrenia in the virtual absence of EPS.
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PMID:[Serotonin antagonism involved in the antipsychotic effect. Confirmation with ritanserine and risperidone]. 169 60

There appears to be a remarkably consistent structural and functional relationship between the phenylethylamine hallucinogens and the microtubule inhibitor colchicine. Such a relationship is not sustained in simple form through to the indoleamine hallucinogens and the indole based Vinca alkaloids. However, LSD and the more potent hallucinogens retain the full potential to disrupt the structure of the brain's cytoskeleton indirectly via serotonin and the raphe system. Serotonin appears to have a direct role in regulating and maintaining microtubules and microfilaments. It appears that a second receptor mediated action is required for full hallucinogenic activity. It is deduced that cytoskeletal restraints may have a role in governing central information processing. A theory for the cellular mechanisms of thought disorder and drug induced hallucinations is proposed. Schizophrenia may reflect a subtle disorder of central cytoskeletal function.
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PMID:The major hallucinogens and the central cytoskeleton: an association beyond coincidence? Towards sub-cellular mechanisms in schizophrenia. 217 86

Risperidone was studied in a 0.16 mg/kg LSD-saline drug discrimination test procedure. At doses varying from 0.0025 to 0.63 mg/kg, no LSD-like agonist effects were observed. Studies on the antagonism of the LSD-cue indicated that risperidone was able to completely block the discriminative stimulus properties of LSD with a minimum ED50-value of 0.028 mg/kg. Risperidone was also very active over time with reference to LSD antagonism, the ED50S after 2, 4 and 8 h pretreatment being 0.028, 0.064 and 0.44 mg/kg. Response rate reductions were only observed at doses greater than or equal to 0.16 mg/kg after 1 h and at 0.63 mg/kg after 2 h pretreatment. Four and 8 h after treatment, no rate-reducing effects were apparent at doses up to 2.50 mg/kg. Thus at pretreatment intervals ranging between 2 and 8 h, complete antagonism of LSD without any rate effects was obtained. As compared to other LSD antagonists, risperidone was quantitatively better than setoperone and ritanserin and longer acting than pirenperone. Based on the pharmacological profile of risperidone and the other LSD antagonists, it was concluded that a potent central 5-HT2 and catecholamine antagonism is needed for a potent and complete antagonism of the 0.16 mg/kg LSD-cue. The potential clinical effect of risperidone in the positive and negative symptoms of schizophrenia is discussed.
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PMID:Risperidone (R 64 766), a potent and complete LSD antagonist in drug discrimination by rats. 247 Dec 20

Methysergide, a congener of LSD and potent serotonin (5-HT) antagonist, induced a florid transient psychosis resembling an LSD psychosis in a patient with spasmodic torticollis with a family history of schizophrenia. Thirteen years later he developed a major depression. A variety of other drug challenges and treatments for his torticollis had no psychotomimetic effect. Blockade of 5-HT receptors may subserve methysergide-induced psychosis.
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PMID:Methysergide-induced psychosis: case report with long-term follow-up. 248 59

Studies of the habituation and sensorimotor gating of startle responses to strong exteroceptive stimuli provide some unique opportunities for cross-species explorations into information processing and attentional deficits in schizophrenia. The behavioral plasticity of startle paradigms greatly facilitates the development of animal models of specifiable behavioral abnormalities in schizophrenic patients. This article reviews the promising findings of studies in which measures of startle have been used to clarify the importance of habituation and central inhibition deficits in schizophrenia. In addition, the development of closely related animal models of habituation and sensory gating of startle is discussed. Such animal model studies allow us to make strong inferences about the neurobiological substrate of schizophrenia. Recent evidence from animal studies of prepulse inhibition provides strong support for a schizophrenia-like loss of sensory gating with nucleus accumbens dopamine overactivity. These data are consistent with hypotheses regarding the significance of mesolimbic dopamine overactivity in schizophrenia. New results are also presented from animal model studies of the effects of serotonergic drugs on startle habituation, extending earlier findings of LSD-induced habituation deficits which are similar to those exhibited by schizophrenic patients. These new data indicate that the serotonergic system, working through serotonin-2 receptors, may play a pivotal role in the modulation of startle habituation. The relationship of serotonergic and catecholaminergic mechanisms is also discussed. Collectively, these studies demonstrate the utility of operationally defined measures of preattentive processes in the study of the neurobiological basis of the group of schizophrenias.
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PMID:Startle habituation and sensorimotor gating in schizophrenia and related animal models. 343 8


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