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)

The varieties of psychotic LSD experiences are many. A very few may resemble a delirium, some are quite reminiscent of schizophrenia and others have an idiosyncratic quality not seen in the naturally occurring psychoses. The psychotic response to LSD is better understood than transcendent experiences because its neurochemistry and phenomenology have been worked out. Additionally, there is greater familiarity with the endogenous psychoses than the endogenous cosmic experiences. The LSD condition, especially the unsane state, is indeed an experience in search of an explanation. It is doubtful that an animal model for it will be found. It is even possible that not all humans are capable of achieving that state by means of the hallucinogenic drugs. The LSD state remains an area of enormous interest that requires exploration and research.
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PMID:LSD: the varieties of psychotic experience. 408 79

It has been reported that the binding of tritiated LSD (at 2 or 4 nm) to frontal cortex is reduced in schizophrenia, a finding that has been interpreted as a reduction in the number of serotonin receptors. The present study, however, reveals in a Scatchard analysis of tritiated LSD binding in frontal cortex in the brains of 13 schizophrenic patients that there was no decrease in binding by comparison with eight control brains. Quantities of neuroleptic remaining in the brain after death cannot be readily washed out and could have led to the previous report of reduced LSD binding. A decrease in affinity of LSD binding sites consistent with this possibility has been demonstrated in chlorpromazine-treated rats. In the brains of five patients who had probably been neuroleptic-free for the year before death, tritiated LSD binding was significantly increased. This result needs to be replicated in larger samples.
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PMID:Tritiated LSD binding in frontal cortex in schizophrenia. 611 1

A 19-year-old man developed a schizophrenia-like psychosis after ingesting isosafrole. His use of amphetamines and LSD failed to produce a similar syndrome. Isosafrole may provide another biochemical model for schizophrenia.
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PMID:Isosafrole and schizophrenia-like psychosis. 646 79

Animal models of human schizophrenia using LSD and related hallucinogens have been challenged on several grounds. One compelling argument against the LSD model is that while schizophrenia can be chronically debilitating, animal and human effects of LSD exhibit behavioral tolerance following chronic administration. The present study tested the effects of acute and chronic LSD on measures of rat startle, a widely used behavioral measure of reactivity and habituation. The results suggest that behavioral tolerance after chronic LSD administration is incomplete, with tolerance exhibited to the acute impairment of habituation but potentiation of startle magnitude on both the first response and the first block of 30 trials. These results are interpreted as supporting the viability of LSD as a model for one or more of the group of schizophrenias.
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PMID:Acute and chronic LSD effects on rat startle: data supporting an LSD--rat model of schizophrenia. 719 55

This paper presents the case report of a 28-year-old man with a rare form of autoscopy. His appearance when he was admitted suggested the possibility of "flash back," due to his long history of abuse of psychotomimetic amphetamines and LSD. The complete psychiatric history and evaluation made it clear that the diagnosis should be that of schizophrenia. He was described as a solitary, withdrawn person, who had lost drive and was emotionally blunted. He often experienced feelings of unreality and appeared to be almost continually deluded and hallucinated. His main delusions were centered on the phenomenon of "autoscopy." The uniqueness of this case is the patient's delusion of watching himself on a television screen acting as one of the "stars."
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PMID:The autoscopic phenomenon: case report and review of literature. 729 67

To date, there is no doubt that dopamine plays a key role in the behavioural disorders associated with schizophrenia. However, dopamine is not the only neurotransmitter involved in this syndrome, as it interacts with many neuronal systems in brain. Of special interest is the interaction between dopaminergic and serotoninergic systems with evidence from pharmacological data in animals that each of these systems may exert an inhibitory influence on the other. Furthermore, the psychotomimetic effects of drugs affecting serotoninergic neurotransmission such as LSD, psilocybin, N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine also contributed to draw attention onto a possible involvement of serotoninergic systems in at least some of the disorders typical of schizophrenia. This idea received strong support from recent studies on the multiple receptors for serotonin in the central nervous system. These studies not only demonstrate the existence of several classes of serotonin receptors called 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2, 5-HT3 and 5-HT4, but led also to the development of novel agonists and antagonists for the stimulation or blockade of each of them. Pharmacological investigations with these ligands revealed that serotonin is probably involved in the behavioural disorders associated with schizophrenia through its binding to three distinct classes of receptors: 5-HT1A, 5-HT2 (or the closely related class 5-HT1C) and 5-HT3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Neuroleptics and serotonin]. 790 21

Hallucinogenic drugs (psychedelics, e.g. Psilocybin, Mescaline, LSD) induce in humans qualitatively altered states of consciousness (ASC), which can be used as experimental models for endogenous psychosis. However, some researchers claim that these ASCs are not appropriate models for schizophrenia. We report two clinical cases of acute endogenous psychoses demonstrating striking similarities to psychedelic experiences. We consider the psychedelic-induced ASC to be an appropriate model for the beginning acute endogenous psychotic episode, but not for the schizophrenic disease as a nosological entity.
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PMID:[Psychedelic experiences at the onset of productive episodes of endogenous psychoses]. 817 61

Serotonin (5-HT) uptake sites were mapped by autoradiographic means with [3H]cyano-imipramine ([3H]CN-IMI), the 5-HT1A receptor with [3H]8-hydroxy-2-[di-n-propyl-amino]tetralin ([3H]8-OH-DPAT), and the 5-HT2 receptor with both [3H]ketanserin and [125I]lysergic acid diethylamide ([125I]LSD) in eight nonneurologic controls and 10 cases with a diagnosis of schizophrenia. In the striatum, there was a marked heterogeneous patterning of 5-HT uptake sites that corresponded to the striosomal/matrix compartmentalization of the striatum. This organization was not matched with an equally heterogeneous pattern of either 5-HT2 or 5-HT1A receptors. For the isocortex, a general organizational scheme was observed with the 5-HT1A receptor expression high in the external laminae and deep laminae, but 5-HT2 receptor expression was higher in the internal laminae. There was a laminar distribution of 5-HT uptake sites that approximated the combined distributions of the 5-HT1A receptor and the 5-HT2 receptor. In the parahippocampal gyrus and hippocampus, the distribution of 5-HT uptake sites was complementary to the distribution of 5-HT1A and 5-HT2 receptors. In schizophrenic cases, there was a large increase in the number and altered striosomal/matrix organization of 5-HT uptake sites in the striatum. There was also an increase in the numbers of 5-HT2 receptors in the nucleus accumbens and ventral putamen of the schizophrenics. The number of 5-HT1A receptors was not modified. There was a marked reduction in 5-HT uptake sites in the external and middle laminae of the anterior cingulate, frontal cortex, and posterior cingulate, and no changes were observed in the motor cortex, temporal cortex, or hippocampus. Increased numbers of 5-HT1A receptors were found in the posterior cingulate, motor cortex, and hippocampus. Serotonin2 receptors were substantially elevated in the posterior cingulate, temporal cortex, and hippocampus, but not in the frontal, anterior cingulate, or motor cortices. Examination of the temporal lobe and hippocampus of a group of nonschizophrenic suicides (n = 8) indicated the alterations in 5-HT system in the limbic regions of the striatum, the limbic cortex, and hippocampus of the schizophrenic cases may be disease specific.
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PMID:Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. 774 66

The hypothesis that the LSD psychosis and by inference schizophrenic psychoses are related to dysfunctions in central serotonergic systems, formulated by Woolley and Shaw in the early 1950s was the first testable theory of modern biological psychiatry. Initially, it did not get the scientific attention it deserved. First, because LSD fell into disrepute and was to all intents and purposes banned from human experimentation. Secondly, the antipsychotics were discovered in the same period, and it became clear that these compounds block dopaminergic transmission and hence for many years thereafter the dopaminergic system occupied center stage in biological schizophrenia research. Presently, interest in the relation between serotonin and schizophrenia has been revived, due to the development of serotonin-blocking agents that appear to exert therapeutic effects in schizophrenia. In this paper the evidence for and against a link between serotonergic defects and schizophrenia psychopathology is critically discussed. The conclusion to be reached is threefold. (1) Interruption of certain serotonergic circuits represents an antipsychotic principle. (2) Tentative evidence suggests the involvement of serotonergic dysfunctions in the pathogenesis of schizophrenic psychoses. (3) It is not yet known whether serotonergic lesions contribute directly to the occurrence of schizophrenic psychopathology or via alterations in the dopaminergic system.
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PMID:The role of serotonin in schizophrenia. 877 54

Aromatic L-amino acid decarboxylase (AADC) is rate limiting in the production of 2-phenylethylamine (2PE). AADC activity and 2PE serum concentrations have been found to be increased in schizophrenic patients. Both antipsychotic and psychotogenic drugs, including amphetamine, affect the activity and encoding mRNA levels of AADC. Amphetamine is an analogue of 2PE and has a similar physiological effect. We have looked at the effects of chronic (32 day) treatment of rats with LSD (0.12 microg/kg/day) and phencyclidine (PCP; 10 mg/kg/day) on AADC mRNA levels. Both drugs up-regulated AADC mRNA levels in striatum, nucleus accumbens, hippocampus and cerebellum by between 50% and 150%. A splicing variant of AADC, present in human brain, which lacks the 3rd exon does not appear to be present in rat brain. These results are consistent with the hypothesis that over activity of AADC leading to increased production of 2PE is involved in endogenous psychosis such as schizophrenia.
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PMID:Does phenylethylamine have a role in schizophrenia?: LSD and PCP up-regulate aromatic L-amino acid decarboxylase mRNA levels. 938 86


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