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Biomedical subjects

T Kolakowska

Publications and source records attributed to T Kolakowska.

At least 19 recordsLinked to original sources

Endocrine responses to tryptophan infusion in schizophrenic patients treated with neuroleptics.

The growth hormone (GH) and prolactin (PRL) responses to intravenous L-tryptophan (LTP) were measured in 20 schizophrenics receiving long-term treatment with neuroleptics and 20 unmedicated control subjects. In the patients, the PRL response was significantly enhanced, and it correlated with PRL baseline concentration. In contrast, the patients' GH response was markedly reduced. These opposite changes in PRL and GH responses to LTP are unlikely to be accounted for by the effect of neuroleptics on serotonin receptors, but they may have been due to the blockade of DA receptors, which is known to disinhibit PRL release and to suppress that of GH.

Adult↗

An open clinical trial of fenfluramine in chronic schizophrenia: a pilot study.

The reports of hyperserotonaemia in chronic schizophrenics and the indications that fenfluramine, a serotonin-releasing drug, may be of therapeutic value in hyperserotonaemic autistic children, were the rationale for this clinical trial. Fenfluramine was administered to 4 treatment-resistant chronic schizophrenic in-patients. They were studied for 14 weeks: 2 baseline weeks, 8 on fenfluramine (maximal dose 120 mg/day for 4 weeks) and 4 post-fenfluramine. Plasma levels of fenfluramine and nor-fenfluramine indicated good compliance. Platelet serotonin concentration decreased in all 4 subjects, weight loss was noted in 2. Clinical changes (assessed by rating psychiatric symptoms and ward behaviour) were observed in 3: moderate sustained improvement in 1, a short-lived activation followed by a slight improvement in another, and a brief amelioration with subsequent worsening in the third. The time and pattern of these changes suggest that they were due to fenfluramine.

Adult↗

Platelet serotonin concentration in schizophrenic patients.

Platelet serotonin (5-HT) concentration did not significantly differ between control subjects (N = 45) and schizophrenic (N = 62) or chronic schizophrenic (N = 39) patients. No clinical feature was associated with hyperserotonemia, but the subgroup receiving benzodiazepines had a significantly higher 5-HT level than other patients.

Adult↗

The effect of lithium on 5-HT-mediated neuroendocrine responses and platelet 5-HT receptors.

The effect of lithium on serotonin (5-HT)-mediated responses in the brain was assessed by measuring changes in the prolactin (PRL) and growth hormone (GH) responses to L-tryptophan (LTP) in eight normal subjects. On the 4th day of lithium treatment the PRL responses were significantly enhanced, and this enhancement was still apparent after 20 days' treatment. In contrast, GH responses to LTP were not altered. Lithium had no effect on platelet 5-HT content, platelet imipramine binding and platelet 5-HT receptor binding. The ability of lithium to enhance some aspects of brain 5-HT function may be important in its mode of action in manic-depressive illness and may be particularly relevant to its potentiation of the antidepressant effect of tricyclic antidepressants.

Adult↗

Tardive dyskinesia in schizophrenics under 60 years of age.

Ninety-one schizophrenics (mean age 34 years) were examined for tardive dyskinesia (TD) during chronic neuroleptic treatment. Dyskinesia was found in 23 (25.3%). The only variable that showed an association with TD was the current doses of neuroleptics: in none of the TD patients did the dose of fluphenazine decanoate (or equivalent) exceed 45 mg/week, whereas it was higher in 23 of the 68 without TD (p less than 0.01). When these 23 "high-dose" patients were disregarded, the TD group differed significantly from the 45 dose-matched non-TD subjects in that it had more common anticholinergic drugs, more common parkinsonian symptoms, and less instances of good remission (p less than 0.05 in each case). There was no association between TD and other considered variables (drug history, age, sex, clinical characteristics, size of the lateral brain ventricles, neurological "soft" signs, cognitive impairment). The results illustrate a relationship between TD prevalence and current doses of neuroleptics and indicate that differences in doses between the groups with and without TD may obscure associations between dyskinesia and other factors.

Adult↗

Responses of prolactin and growth hormone to L-tryptophan infusion: effects in normal subjects and schizophrenic patients receiving neuroleptics.

Intravenous infusion of L-tryptophan (LTP) in 18 normal subjects produced a significant increase in plasma prolactin (PRL), growth hormone (GH), and self-ratings of drowsiness. There was no correlation between the PRL and GH responses, or between the hormonal responses and drowsiness. Saline infusion did not result in endocrine or psychological changes. The effect of LTP on both PRL and GH was dose-related in that LTP 7.5 g produced greater endocrine responses than 5.0 g. It was not significantly decreased by cyproheptadine, a 5-HT receptor antagonist. Schizophrenic patients receiving neuroleptics had increased PRL response to LTP, possibly because of the drug-induced disinhibition of PRL release. Their GH response to LTP was markedly decreased. The mechanism of this effect requires further investigation.

Adult↗

Schizophrenia with good and poor outcome. I: Early clinical features, response to neuroleptics and signs of organic dysfunction.

Seventy-seven patients with diagnosis of schizophrenia (62) or schizoaffective disorder (15) were studied 2-20 years since onset of illness, when in a stable condition. The investigation included clinical assessment, measurement of plasma concentrations of neuroleptics and prolactin, computed tomography brain scan, neuropsychological and neurological examination. Outcome of illness was classified according to the presence of chronic psychiatric symptoms and social impairment, and response to neuroleptics according to the effect of treatment in the most recent psychotic episode. Neither outcome nor response to neuroleptics was related to duration of illness. The groups with good and poor outcome differed in premorbid adjustment, age at onset and symptoms of the initial episode, but not in drug bio-availability or prolactin response. Large cerebral ventricles and cognitive impairment, but not neurological 'soft' signs, were associated with unfavourable outcome. The three measures of organicity were not inter-related. No clinical differences were found between chronic patients with and without signs of organic dysfunction. The findings suggest that schizophrenia with good and unfavourable outcome may be separate sub-types. However, the role of organic factors in the latter group remains unclear.

Adult↗

Schizophrenia with good and poor outcome. II: Cerebral ventricular size and its clinical significance.

Computer tomography brain scans were carried out on 40 patients with schizophrenia or schizo-affective disorder of 2-20 years duration. Ventricular-brain ratio (VBR) was significantly greater than that of the control group. In six patients the VBR exceeded the control mean + 2 s.d. Among the 13 whose VBR was more than 1 s.d. above the control mean, none had schizo-affective disorder, all but one had chronic illness, and patients with negative symptoms and those with premorbid schizoid traits were over-represented. VBR was unrelated to medical history, age, duration of illness, or neuroleptic treatment. It was not associated with neurological 'soft' signs or cognitive deficit. Among chronic patients, clinical features showed no association with ventricular size. The findings suggest that large ventricles may be related to a sub-type of chronic schizophrenia rather than to its particular clinical features.

Adult↗

Schizophrenia with good and poor outcome. III: Neurological 'soft' signs, cognitive impairment and their clinical significance.

Fifty-six patients with RDC schizophrenia (42) or schizoaffective disorder (14), of two to 20 years' duration, were assessed for neurological 'soft' signs and cognitive impairment when in a stable condition--the 'outcome'. Neurological dysfunction (46% of 50 examined patients) was associated with a history of developmental abnormalities, but was unrelated to outcome, psychiatric symptoms, or treatment. Deficits in particular cognitive fields were related to two independent factors: overall severity of residual psychiatric disorder (outcome) and neurological dysfunction. There was no relationship between the size of the lateral brain ventricles on CT scan and either 'soft' signs or cognitive impairment. The findings do not provide evidence for an association between the presence of organic brain disorder (as indicated by the joint occurrence of neurological dysfunction and cognitive impairment) and either poor outcome or particular symptoms of schizophrenia.

Adult↗

Growth hormone and prolactin response to apomorphine in schizophrenia and the major affective disorders. Relation to duration of illness and depressive symptoms.

The responses of serum prolactin (PRL) and growth hormone (GH) to the dopamine agonist apomorphine hydrochloride (0.75 mg subcutaneously) were studied in a large group of unmedicated hospitalized patients with functional psychoses. There were no differences in the GH response in various diagnostic groups. The PRL response was greater in patients with affective disorders. The GH response was inversely related to total duration of illness in the entire sample of patients, but this correlation was independent of age effect only in the group of patients with major depression. In schizophrenics, the effect of the two factors, age and duration of the illness, could not be separated. The apomorphine-induced GH response was significantly correlated with psychosis ratings and negative symptom scale scores. The apomorphine-induced PRL suppression correlated significantly with various measures of depression across diagnostic groups.

Adolescent↗

Effect of low-dose bromocriptine in treatment of psychosis: the dopamine autoreceptor-stimulation strategy.

Bromocriptine (0.5-6.0 mg/day) was administered to seven unmedicated chronic schizophrenic and two schizoaffective patients. Transient slight improvement was noted in four patients and marked improvement in one other. Clinical improvement was associated with nausea and drowsiness. These doses of bromocriptine stimulated serum growth hormone and inhibited serum prolactin levels in some subjects. These results suggest that bromocriptine may stimulate dopamine autoreceptors and, through this mechanism, attenuate symptoms in a small proportion of psychiatric patients.

Brain Chemistry↗

Neuroendocrine tests during treatment with neuroleptic drugs: I. Plasma prolactin response to chlorpromazine challenge.

Chlorpromazine (CPZ) 50 mg IM was administered to 21 schizophrenics receiving neuroleptic treatment. A further increase in plasma prolactin (PRL) was provoked in 8 subjects who had lower daily doses of neuroleptics than the remainder. The difference in the baseline PRL concentrations between the subgroups was inconsistent. In some patients, the test dose produced no change in plasma PRL but a further PRL rise was induced by raising the challenge dose or by an increase in the daily dose of neuroleptics. It is concluded that the PRL rise following CPZ 50 mg IM identifies some patients whose PRL response to the current treatment was only submaximal but the absence of PRL increment after this test dose is not sufficient evidence that the baseline level was already maximal.

Adult↗

A survey of prescribing psychotropic drugs in two psychiatric hospitals.

Of 511 patients in two psychiatric hospitals, one-fifth had no psychotropic drugs, but over one-third (nearly half of those receiving medication) had a combination of two or more psychotropic drugs. Hypnotics and minor tranquillizers were commonly prescribed together with neuroleptics and anti-depressants. One-fifth of day-patients treated with depot neuroleptics also has oral neuroleptics. Anti-parkinsonian drugs were prescribed for half of those receiving neuroleptics. Both minor tranquillizers and neuroleptics were commonly administered three or more times a day. Forty per cent of patients treated with neuroleptics had diagnoses other than schizophrenia, and one-third of those receiving antidepressants had diagnoses other than affective disorder. An analysis of prescribing could contribute to a more rational use of psychotropic drugs.

Drug Therapy, Combination↗

Neuroendocrine tests during treatment with neuroleptic drugs I. Plasma prolactin response to haloperidol challenge.

The plasma prolactin (PRL) response to haloperidol 2 or 4 mg i.m. was studied in 18 schizophrenic men during their routine treatment with neuroleptic drugs. A substantial rise of the PRL level above the treatment baseline occurred in all but four of the 20 tests showing that the PRL elevation induced by treatment was not maximal. The challenge was ineffective only in patients receiving very high daily doses of medication. The increment was inversely correlated to the daily dose of medication but unrelated to plasma haloperidol concentrations during the test. Chronic schizophrenics who were receiving long term treatment and had low basal PRL levels did not show tolerance to the prolactin stimulating effect of haloperidol. That prolactin rose during the test in patients who had improved during their current treatment indicates that the degree of dopamine receptor blockade required for therapeutic effects is below that which produces a maximal PRL response.

Adult↗

Neuroendocrine tests during treatment with neuroleptic drugs. III. Plasma growth hormone and prolactin responses to apomorphine.

Hormonal responses to apomorphine 0.005 and/or 0.01 mg/kg body weight were studied in 17 schizophrenic patients during their routine treatment with neuroleptic drugs. Plasma growth hormone (GH) rose in 9 of the 20 tests and in 4 of these GH peak exceeded 5 ng/ml. This preserved GH response to apomorphine was significantly but weakly associated with lower daily doses of neuroleptics. It was unrelated to the extrapyramidal side-effects, plasma prolactin (PRL) level, duration of treatment or its therapeutic effect. In 13 of the 20 tests, plasma PRL declined by more than 20 per cent of the baseline level. This was similar to the fall in PRL observed after placebo in the group studied previously. The absolute decline in plasma PRL following apomorphine correlated positively with the baseline PRL concentration and was unrelated to the daily doses of neuroleptics or to any other variable considered.

Adult↗