Dementia praecox and schizophrenia: was Bleuler wrong?
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to T J Crow.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Urinary MHPG excretion in patients with acute schizophrenia was studied before and during a trial of the isomers of flupenthixol and placebo. Pretrial MHPG excretion was not related to severity of illness before the trial or to other pretrial clinical variables. In male subjects higher pretrial MHPG excretion was associated with a better outcome 1 year post-trial. However in females no relationship between MHPG excretion and outcome was established. During the trial there was a reduction in MHPG excretion in patients treated with beta-flupenthixol but no decrease in the group treated with alpha-flupenthixol or chlorpromazine. In patients on placebo there was a reduction in MHPG excretion in those who did well clinically, but not in those who did poorly. Thus low MHPG excretion may be a predictor of poor outcome in schizophrenia, but MHPG excretion also changes both as a function of clinical state and of neuroleptic drug administration.
Serotonin (5HT), its chief metabolite 5-hydroxyindoleacetic acid (5 HIAA), its precursor tryptophan, and kynurenine, another metabolite of tryptophan, have been measured in post mortem human brain samples. Concentrations of these metabolites were not found to be significantly different in putamen, hippocampus or temporal cortex from 23 normal subjects compared with 15 subjects in whom a diagnosis of schizophrenia could be restrospectively confirmed. The results have been analysed with respect to cause of death, medication and post mortem changes. Post mortem increases in tryptophan and kynurenine were observed. Some interrelationships between the variables measured within and between the different areas studied are discussed. It is concluded that there is no evidence for a generalised deficit of 5HT in the brain in schizophrenia, nor for gross changes in turnover along the serotonin or kynurenine pathways of tryptophan metabolism in brain.
Cerebrospinal fluid from 13 of 38 patients with schizophrenia had a cytopathic effect in cultures of MRC5 cells. The cytopathic agent passed a 100 nm but not a 50 nm filter and was unaffected by heat at 56 degrees C for 30 min, treatment with chloroform, or the presence in cultures of bromodeoxyuridine. The agent could not be propagated serially in a satisfactory manner but its properties were those of a virus. A similar cytopathic effect was induced by cerebrospinal fluid from 8 of 11 patients with serious or chronic nervous system disease but only 1 of 25 patients with surgical or general medical conditions.
A virus-like agent (V.L.A.) with a cytopathic effect on cultured cells was found in the cerebrospinal fluid of 18 of 47 patients with schizophrenia, of whom 10 had nuclear schizophrenic symptoms. In most patients with V.L.A., blood and C.S.F. protein concentrations were normal. Patients with and without V.L.A. had similar clinical characteristics but serum IgA levels were higher in those with V.L.A. V.L.A. was also detected in the C.S.F. of 8 of 11 patients with serious or chronic neurological disease (Huntington's chorea, multiple sclerosis, and unexplained alterations of consciousness).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The diagnosis of schizophrenia is established principally by the presence of certain psychological symptoms which although subjective can be reliably assessed by standardized interviewing procedures. The most characteristic symptoms (Schneider's first-rank symptoms) fall into three groups: (a) auditory hallucinations of particular types, (b) 'ego-boundary disturbances', including intrusions into the stream of consciousness attributed to external agencies, and (c) delusional perception. Symptoms closely resembling those seen in schizophrenia can be induced in non-schizophrenic individuals by amphetamine-like drugs, and both these symptoms and those of schizophrenia are ameliorated by neuroleptic drugs (the major tranquillizers). Amphetamines facilitate and neuroleptic drugs diminish neural transmission mediated by the chemical substance dopamine. In recent post-mortem studies on patients who had suffered brom schizophrenia, it was found that dopamine release was not increased. However, in some cases there was evidence of increased sensitivity of the dopamine receptor.
Plasma levels of flupenthixol were estimated by three methods in 30 patients with acute schizophrenia and 29 patients with chronic schizophrenia. These levels were related to clinical response, anterior pituitary hormone secretion, platelet monoamine oxidase activity, the effects of the concurrent administration of anticholinergic drugs, and body weight. No clearcut relationships between plasma flupenthixol levels and any of these variables were demonstrated. The practical clinical value of the estimation of plasma flupenthixol is limited at the present time.
Skin conductance responses to a series of tones were measured in 41 patients during an acute episode of schizophrenia before they received treatment and after 4 weeks of treatment with either alpha-flupenthixol, beta-flupenthixol or placebo. Patients who did not habituate to the tones prior to treatment tended to show no symptomatic improvement during the course of treatment. Patients who habituated and also showed an acute onset of their current symptoms ('Feighner negative' patients) showed a marked improvement even without active medication. Skin conductance responsivity did not change with improvement in symptoms alone, but decreased in patients on active medication (alpha-flupenthixol). Non-habituation of skin conductance and insidious onset (i.e. fulfilment of the Feighner criteria) were found to be independent predictors of poor outcome. Taken together, these criteria may define a group of patients with particularly poor prognosis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Dopamine and its metabolites homovanillic acid and dihydroxyphenylacetic acid, noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid, and tryptophan and its metabolite kynurenine have been assayed in 9 schizophrenic and 10 control brains, together with the monoamine-related enzymes tyrosine hydroxylase monoamine oxidase, dopamine-beta-hydroxylase, and catechol-o-methyl-transferase. In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined. The findings are not consistent with theories that serotonin or noradrenaline stores are grossly depleted or noradrenaline neurones have degenerated, or that monoamine oxidase activity is abnormal, in schizophrenia, and provide no direct support for the hypothesis that dopamine neurones are overactive.
Two catecholamine-containing pathways, the locus ceruleus system and the dopamine neurons arising from the ventral mid-brain, may be involved in reward. Dopamine neurons function as a system for energizing the organism's responses and directing them toward significant environmental stimuli, but the functions of the locus ceruleus system remain obscure. It appears increasingly likely that neuroleptic drugs exert their anti-psychotic effects in acute schizophrenia by blocking dopamine receptors, although the time course of the effect suggests that the mechanism is more complex than a simple reversal of a neurohumoral imbalance. Evidence from postmortem studies suggests that, at least in the chronic state, dopamine turnover is not increased, but that there may be an increase in postsynaptic receptor density in some cases, including some patients who apparently had not received medication in the year before death. The evidence is consistent with Olds and Travis' conjecture that "counteraction of positive feedback processes subserving positive reinforcement mechanisms may be a key to control of certain psychotic episodes".
Explore the source record for details and available documents.
Explore the source record for details and available documents.