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Biomedical subjects

T J Crow

Publications and source records attributed to T J Crow.

At least 361 records · Page 20Linked to original sources

The activities of brain dopamine-beta-hydroxylase and catechol-O-methyl transferase in schizophrenics and controls.

It has been suggested that deterioration of central noradrenergic pathways may be responsible for the production of certain schizophrenic symptoms, and that such a degeneration might be reflected in lowered dopamine-beta-hydroxylase (DBH) activity in the brains of schizophrenics. The present study revealed that in rats lowered DBH activity was a sensitive index of noradrenergic degeneration. In the postmortem brains of 12 controls and 12 schizophrenics, however, no significant difference in DBH activity between controls and schizophrenics was found. DBH activity was relatively unstable postmortem and adversely affected by neuroleptic drugs, and these factors may have contributed to the previous finding of lowered DBH activity in the brains of schizophrenics. The activity of catechol-O-methyl transferase, which has also been previously reported as low in the brains of schizophrenics, was found to be no different in the controls of the present study.

Animals↗

The locus coeruleus noradrenergic system--evidence against a role in attention, habituation, anxiety and motor activity.

Lesions of the locus coeruleus system were induced by combined stereotaxic injections of 6-OH-dopamine to the ascending fibres and just lateral to the locus coeruleus itself, to deplete the noradrenaline content of both the cerebral and cerebellar cortices. A group of rats with cortical noradrenaline concentrations of less than 30 ng/g were compared with a group with lesser destruction of the system (mean noradrenaline concentration 71 +/- 44 ng/g) and with controls (mean noradrenaline 347 +/- 58 ng/g). Lesioned rats showed normal motor activity and exploration (assessed with a holeboard) and showed normal habituation of these behaviours. The lesioned rats gave no evidence of increased susceptibility to distracting auditory stimuli whilst licking for water, and the groups did not differ in their rate of habituation to these stimuli, or in dishabituation. In a social interaction test, lesioned animals showed a decrease in social contacts in an unfamiliar situation (interpreted as a response to anxiety) of similar magnitude to that seen in the control group. In this test, lesioned animals engaged in more 'aggressive' behaviour (boxing and wrestling) than did the controls. These findings are incompatible with hypotheses that the locus coeruleus system is an integral part of the physiological mechanisms which control gross motor behaviour, attention, habituation or anxiety. Together with previous findings with the benzodiazepines, the results with the social interaction test make it unlikely that the benzodiazepines exert their anxiolytic effects by inhibiting the locus coeruleus system.

Acoustic Stimulation↗

Retention of an associative behavioral change in Hermissenda.

The nudibranch mollusk Hermissenda crassicornis is normally attracted to a test light. Three days of training consisting of 50 trials per day of light paired with a rotational stimulus led to a significant increase, lasting for days, in the animal's response latency to enter a test light. The group that received light associated with rotation was significantly different from groups subjected to nonassociative control procedures. Modifications of well-known sensory networks may be related to a behavioral change that shares several operational features with associative learning.

Animals↗

How does E.C.T. work?

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Clinical Trials as Topic↗

Increased dopamine-receptor sensitivity in schizophrenia.

Dopaminergic mechanisms have been investigated in post-mortem brain specimens from nineteen patients with schizophrenia and nineteen controls. Dopamine turnover was not increased in schizophrenic patients but, as assessed by the spiroperidol-binding technique, there was a significant increase in postsynaptic receptor sensitivity. The change in the dopamine receptor occurred in nucleus accumbens, putamen, and caudate nucleus. Increased dopamine-receptor sensitivity was present in five patients who had been free of neuroleptic medication for at least 1 year before death, and therefore may be related to the disease process.

Aged↗

Methodological problems in the measurement of drug-induced rotational behaviour: continuous recording reveals time-course differences undetected by previous techniques.

Rats were lesioned unilaterally in the medial forebrain bundle with either the catecholamine neurotoxin 6-hydroxydopamine or the indoleamine neurotoxin 5,6-dihydroxytryptamine. Their rotational responses in automated rotameters to a challenge with the dopamine-receptor agonist apomorphine were compared using four different techniques in current use, and by assessment of complete rotation curves using both conventional statistical procedures and elementary computer-derived elements of curvature. The rotational responses of the two groups, characterized neurochemically by identical depletions of striatal dopamine but with a greater depletion of striatal 5-hydroxytryptamine in 5,6-dihydroxytryptamine-lesioned animals, were indistinguishable using each of the four current techniques. Assessment of rotation curves by both methods revealed significant differences between the two groups, characterised by faster onset and offset of the rotational response in 5,6-dihydroxytryptamine-lesioned animals. Some current techniques may implicitly exclude the detection of such time-course differences in rotational behaviour. Assessment of complete rotation curves may best allow valid comparisons between experimental groups.

5,6-Dihydroxytryptamine↗

Mechanism of the antipsychotic effect in the treatment of acute schizophrenia.

In a double-blind trial in which 45 patients with acute schizophrenia took part the alpha-isomer of flupenthixol (which blocks the dopamine receptor) was found to be significantly more effective than both beta-flupenthixol (which does not) and placebo. The drug effect was confined to the "positive" symptoms--delusions, hallucinations, and though disorder--and appeared only in the 3rd and 4th weeks of the trial. It was as great in patients with evidence of deterioration (Feighner-positive patients) as in patients without deterioration and was less in patients who had affective disturbance in addition to schizophrenia symptoms. The findings are consistent with the hypothesis that dopamine-receptor blockade is the only requirement for antipsychotic activity and suggest that the antipsychotic effect occurs in patients with typically schizophrenic illnesses but may be limited to positive symptoms.

Acute Disease↗

Neuroendocrine changes in acute schizophrenia as a function of clinical state and neuroleptic medication.

Changes in levels of prolactin, growth hormone, luteinizing hormone, and follicle stimulating hormone in serum, and testosterone in plasma, have been studied in 38 patients with acute schizophrenic illnesses in a 4-week double-blind comparison of the 2 isomers of flupenthixol and placebo. Only prolactin showed changes which could be related either to changes in clinical state or to the effects of medication. Prolactin levels increased during treatment with the therapeutically active alpha-isomer of flupenthixol but were unchanged with the inactive beta-isomer and placebo. Although there was a significant relationship between prolactin level and antipsychotic effect in patients on alpha-flupenthixol, in the individual case prolactin level was not a strong predictor of therapeutic response; and in patients on inactive medication changes in prolactin level could not be related to sympton change. There was a time lag of at least 2 weeks between the increase in prolactin secretion in patients on alpha-flupenthixol and the therapeutic effect attributable to medication. This delay suggests that if the antipsychotic effect is dependent upon dopamine receptor blockade it is not a direct consequence of this action. Perhaps dopamine receptor blockade permits other, and slower, changes to take place and it is these changes, rather than dopamine receptor blockade itself, which are reflected in clinical improvement.

Acute Disease↗

Viral causes of psychiatric disease.

Current evidence on the role of viruses in the causation of psychiatric illness is reviewed. Herpes simplex encephalitis is relatively well defined but a wider role for this virus, particularly in relation to affective disorders, is suggested by some Scandinavian surveys of antibody titres in psychiatric populations. The extent to which influenzal illnesses and infectious mononucleosis may lead to neurotic, and occasional psychotic, episodes is the subject of controversy. The clinical literature is reviewed on the occurrence of encephalitis-like illnesses with prominent psychiatric and behavioural features. It is pointed out that no reliable criterion exists for differentiating these illnesses from such psychiatric syndromes as schizophrenia. It is suggested that neglect of this borderland area, and perhaps preconceptions concerning the features of 'organic' and 'functional' psychiatric disease, may have led to an underestimate of the possible role of viruses in the causation of psychiatric disease.

Cerebrospinal Fluid↗

Age disorientation in schizophrenia: a constant prevalence of 25 per cent in a chronic mental hospital population?

The prevalence of age disorientation was estimated in the population of patients with a diagnosis of schizophrenia in a large mental hospital. Of these 357 patients 25 per cent demonstrated age disorientation, defined as a five-year discrepancy between true and subjective age, and 11 per cent of the population believed themselves to be within five years of the age they were at admission, although they were a mean 28.9 years older. Age-disorientated patients differed from the age-orientated in being significantly older. However, when age-matched, they were younger at first admission and had a longer duration of stay than patients with a diagnosis of schizophrenia without age-disorientation. Age-disorientation may thus be a feature of a type of schizophrenic illness of early onset and poor prognosis.

Adult↗

Age disorientation in chronic schizophrenia: the nature of the cognitive deficit.

In an interview survey of temporal orientation in chronic schizophrenia, patients with age disorientation (n = 77) were much less likely than patients without age disorientation (n = 222) to be able to give correct answers to simple questions about dates and the passage of time (e.g. their date of birth, the present year and the duration of their hospital stay). The age disorientated systematically under-estimate the present year and their duration of hospital stay; in individual patients the errors they make are consistent with their concept of their own age. "Time stands still" for these patients. However, there are patients in whom an incorrect appreciation of their own age co-exists with correct awareness of the present year. Between these patients and those for whom subjective time stands still, there appears to be a continuum of increasing temporal disorientation. This dimension may be a clinical correlate of intellectual impairment.

Age Factors↗