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Biomedical subjects

T R Barnes

Publications and source records attributed to T R Barnes.

At least 37 records · Page 2Linked to original sources
PubMed1998

Novel antipsychotics, extrapyramidal side effects and tardive dyskinesia.

A common and serious drawback of the conventional antipsychotics is their association with a range of motor disturbances: acute extrapyramidal symptoms, including parkinsonism, acute akathisia and acute dystonia; and chronic motor problems such as tardive dyskinesia, chronic akathisia and tardive dystonia. In addition to physical disability directly related to abnormal movements, the acute movement disorders can cause considerable subjective discomfort and distress, and are frequently cited as a reason for poor compliance with medication, at least during acute treatment. They can also confound clinical assessment of mental-state phenomena because of symptom overlap with the psychotic illness being treated. The results of clinical trials of the newer antipsychotic drugs such as clozapine, risperidone, olanzapine, amisulpride, quetiapine and sertindole suggest a lower liability for acute extrapyramidal symptoms than conventional antipsychotic drugs such as haloperidol and chlorpromazine. The relative liability of each of the newer drugs to cause acute extrapyramidal side effects is not known, as they have been available for a relatively short time and there is a paucity of direct comparative studies. Evidence is accumulating that those patients exhibiting acute extrapyramidal side effects are at greater risk of developing tardive dyskinesia, which raises the hope that the newer antipsychotic drugs may also be associated with less tardive dyskinesia in the longer term. Encouraging data are already available for clozapine, which appears to have a low incidence of tardive dyskinesia, and therapeutic value in a proportion of established cases of tardive dyskinesia and tardive dystonia. Here we review the available data on atypical antipsychotics and adverse motor effects.

Antipsychotic Agents↗
PubMed1998

Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia.

OBJECTIVE: A pilot study of the density of dendritic spines on pyramidal neurons in layer III of human temporal and frontal cerebral neocortex in schizophrenia. METHODS: Postmortem material from a group of eight prospectively diagnosed schizophrenic patients, five archive schizophrenic patients, 11 non-schizophrenic controls, and one patient with schizophrenia-like psychosis, thought to be due to substance misuse, was impregnated with a rapid Golgi method. Spines were counted on the dendrites of pyramidal neurons in temporal and frontal association areas, of which the soma was in layer III (which take part in corticocortical connectivity) and which met strict criteria for impregnation quality. Altogether 25 blocks were studied in the schizophrenic group and 21 in the controls. If more than one block was examined from a single area, the counts for that area were averaged. All measurements were made blind: diagnoses were only disclosed by a third party after measurements were completed. Possible confounding affects of coexisting Alzheimer's disease were taken into account, as were the effects of age at death and postmortem interval. RESULTS: There was a significant (p<0.001) reduction in the numerical density of spines in schizophrenia (276/mm in control temporal cortex and 112/mm in schizophrenic patients, and 299 and 101 respectively in the frontal cortex). An analysis of variance, taking out effects of age at death and postmortem interval, which might have explained the low spine density for some of the schizophrenic patients, did not affect the significance of the results. CONCLUSION: The results support the concept of there being a defect in the fine structure of dendrites of pyramidal neurons, involving loss of spines, in schizophrenia and may help to explain the loss of cortical volume without loss of neurons in this condition, although the effect of neuroleptic drugs cannot be ruled out.

Adult↗
PubMed1997

Detecting comorbid substance misuse among people with schizophrenia in the community: a study comparing the results of questionnaires with analysis of hair and urine.

Substance misuse among people with schizophrenia is thought to be common and to adversely affect the outcome of the illness. The shortcomings of studies in this area include patient samples that are not epidemiologically-based, and methods for detecting substance misuse that have serious limitations. We investigated the frequency and severity of substance misuse among people with schizophrenia living in the community in London. Interviews were conducted with a community-based sample of 39 people with schizophrenia aged 35 years or less, living in Inner London. The assessments included ratings of psychopathology, movement disorders and substance misuse, and co-informant histories. Urine and hair specimens were analysed for a range of substances. Urine samples were collected from 37 patients and hair samples were provided by 36 patients. Comorbid substance misuse was reported or detected in 63% of the sample. The information elicited using a structured questionnaire for both informants and subjects represented an under-estimate of psychostimulant misuse and opiate misuse compared with the results obtained by hair or urine analysis. Hair analysis revealed that 12 (33%) of those patients providing samples had covertly abused amphetamines, opiates or cocaine in the previous 3 months. The study demonstrated that hair analysis is a well-tolerated, sensitive test for substance misuse. The technique has several advantages over questionnaires and urine analysis for clinical and research purposes. Further applications include the assessment of comorbid substance use in particular groups of patients with schizophrenia, such as during first-episode or psychotic relapse, or those with forensic problems or apparent resistance to treatment.

Adult↗
PubMed1997

Frontal-striatal cognitive deficits in patients with chronic schizophrenia.

Spatial working memory and planning abilities were assessed in 36 hospitalized patients with chronic schizophrenia, using the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB), and compared with those of normal subjects and patients with neurological disorders (frontal lobe lesions; temporal lobe and amygdalohippocampal lesions; Parkinson's disease), matched for age, sex and National Adult Reading Test IQ. The patients in the group with temporal lobe lesions were unimpaired in their performance on these tasks. Patients with schizophrenia were impaired on visuo-spatial memory span compared with all the other groups, while severity of Parkinson's disease was correlated with the degree of impairment on this task. The patients with schizophrenia and those with frontal lobe lesions were impaired on a 'spatial working memory' task, with increased 'between-search errors'. Patients with Parkinson's disease performed this task poorly compared with the younger control subjects. Patients with schizophrenia were unable to develop a systematic strategy to complete this task, relying instead on a limited visuo-spatial memory span. Higher level planning ability was investigated using the CANTAB 'Tower of London'. All groups were equally able to complete the task. However, the groups of patients with schizophrenia and frontal lobe lesions made fewer perfect solutions and required more moves for completion. Movement times were significantly slower in the schizophrenia group, suggesting impairment in the sensorimotor requirements of the task. The patients with schizophrenia were not impaired in their 'initial thinking' (planning) latencies, but had significantly prolonged 'subsequent thinking' (execution) latencies. This pattern resembled that of the group with frontal lobe lesions and contrasted with the prolonged 'initial thinking' time seen in Parkinson's disease. The results of this study are indicative of an overall deficit of executive functioning in schizophrenia, even greater than that seen in patients with frontal lobe lesions. However, the pattern of results in schizophrenia resembled that seen in patients with lesions of the frontal lobe or with basal ganglia dysfunction, providing support for the notion of a disturbance of frontostriatal circuits in schizophrenia. Our findings also indicate that there is a loss of the normal relationships between different domains of executive function in schizophrenia, with implications for impaired functional connectivity between different regions of the neocortex.

Adolescent↗
PubMed1997

One-year, low-dose neuroleptic study of in-patients with chronic schizophrenia characterised by persistent negative symptoms. Amisulpride v. haloperidol.

BACKGROUND: Amisulpride is a potent substituted benzamide antipsychotic drug claimed to improve the negative symptoms of schizophrenia, particularly at low dosage. METHOD: Sixty long-term in-patients with schizophrenia and selected for predominant negative symptoms were randomised to receive either haloperidol or amisulpride. Over a year there was systematic dose reduction, as symptoms allowed. RESULTS: There were no significant differences between the treatment groups in the proportion receiving low-dose treatment, the control of positive symptoms, or ratings of social behaviour, side-effects or tardive dyskinesia. For negative symptoms, there were consistent but non-significant trends in favour of amisulpride. The amisulpride patients required significantly less anticholinergic medication. CONCLUSIONS: In chronically-hospitalised in-patients with schizophrenia characterised by persistent negative symptoms, amisulpride was a well-tolerated maintenance antipsychotic medication. The drug had only a limited effect in reducing negative symptoms, which were relatively stable, enduring phenomena in this sample, despite dosage reduction.

Adult↗
PubMed1996

Movement disorder in Down's syndrome: a possible marker of the severity of mental handicap.

This study examined the nature and prevalence of abnormal movements in adults with Down's syndrome and also the clinical correlates of orofacial dyskinesia and the relationship between dyskinesia and the level of functional and intellectual disability. Movement disorder, language age, and disability were assessed in an epidemiologically based sample of 145 individuals with Down's syndrome. Abnormal involuntary movements were common, with > 90% exhibiting dyskinesia, predominantly orofacial. Stereotypes were present in one-third of the sample. There was an association between the severity of dyskinesia and both current language age and functioning in terms of self-care and practical and academic skills, which suggested that dyskinesia may be a marker of the severity of mental handicap. The presence of dyskinesia was unrelated to neuroleptic exposure. Dyskinesia and stereotypies are very common in individuals with Down's syndrome and may represent an inherent manifestation of the disorder. The relationship between mental age and dyskinesia in Down's syndrome warrants further research.

Activities of Daily Living↗
PubMed1996

Pharmacological treatment strategies in the non-responsive schizophrenic patient.

The care of people with schizophrenia that has failed to respond to conventional antipsychotic medication remains a formidable challenge. However, the introduction of clozapine heralded a new optimism in this area, and prompted an increase in research interest in the pharmacotherapeutic options for such patients. This brief review covers some of the more recent studies with clozapine that are relevant to the use of the drug in clinical practice, and also summarises the potential indications, benefits and limitations of various adjuncts to antipsychotic drug treatment.

Antipsychotic Agents↗
PubMed1996

Electrocardiographic changes in patients receiving neuroleptic medication.

The precise aetiology of sudden death in patients receiving neuroleptic medication is uncertain, but cardiac arrhythmias are a possible cause. We investigated the link between neuroleptic medication and electrocardiographic changes predictive of malignant cardiac arrhythmias. Electrocardiographs were performed on 111 patients receiving neuroleptic medication and on 42 unmedicated controls. Prolonged QTc intervals were more common in the patient sample, but QTc dispersion was not significantly increased. QTc interval prolongation was more likely in patients on doses above 2000 mg chlorpromazine equivalents daily (odds ratio 4.28, P < 0.02). Neuroleptic medication, especially at high doses, is associated with ECG changes that may herald more serious cardiac problems.

Adult↗
PubMed1996

Delusional misidentification: the illusion of Fregoli and a dog.

Misidentification syndromes have been regarded as psychiatric curious, but in recent years their importance both in terms of frequency, and because of their links with organic brain pathology and risk of violence has been increasingly realised. Most of the cases reported have been in conjunction with schizophrenia. We report a case of the illusion of Fregoli, the delusional misidentification of a familiar person in a stranger. The patient was manic and exhibited the delusion twice, once with regard to a man and the other concerning a dog.

Adult↗
PubMed1996

Psychopathology, social and cognitive functioning in a hostel for homeless women.

BACKGROUND: This study surveyed all residents in a hostel for homeless women. Demographic data, and information on past and present psychiatric and social morbidity, and current and premorbid cognitive functioning were collected. METHOD: A four week prevalence study, using: SCID-PD; a semi-structured interview; GHQ; SBS; Manchester Scale; MMSE; and NART; the data were analysed using SPSS. RESULTS: The women originated from across the social spectrum and disruption of early family life was common. Fifty per cent had a 'severe mental illness' and most were not receiving drug treatment. High levels of active psychotic symptoms were present. Women with psychosis had suffered a greater intellectual decline from their premorbid levels of functioning than those without psychosis. CONCLUSIONS: The study affirmed findings of earlier studies employing case-studies methodology. Women with high levels of psychiatric morbidity and social dysfunction were being managed by care workers in a way that may promote stability rather than a drift into street-life.

Adolescent↗
PubMed1996

Four behavioural syndromes of schizophrenia.

BACKGROUND: A complementary approach to defining symptomatic subtypes of schizophrenia is to identify characteristic patterns of 'problem behaviours' associated with the capacity of patients to function in the community. METHOD: In a large epidemiological survey, patients fulfilling Feighner criteria for schizophrenia were identified by key informants and assessed using the MRC Social Behaviour Schedule (SBS) and the Manchester Scale. An exploratory factor analysis was used to extract behavioural syndromes from the SBS data in order to compare the syndrome profiles in community, acute and long-stay subgroups and to examine their associations with symptoms and social functioning. RESULTS: Four behavioural syndromes were identified: 'Thought disturbance', 'Social withdrawal', 'Depressed behaviour' and 'Anti-social behaviour', which distinguished between the patient subgroups and had significant differential relationships to symptoms and social functioning variables. CONCLUSIONS: The evaluation of disability in schizophrenia and effectiveness of treatment interventions is incomplete without an assessment of problem behaviours.

Adult↗
PubMed1996

Cognitive function and duration of rooflessness in entrants to a hostel for homeless men.

BACKGROUND: Four previous studies of homeless adults have yielded conflicting results regarding the presence of cognitive impairment. METHOD: A consecutive series of 80 roofless entrants to a hostel for homeless men were sampled and 62 (76%) completed a range of assessments, including measures of mental state, cognitive functions and substance use. RESULTS: Estimated premorbid IQ (mean = 96), current IQ (mean = 84) and cognitive speed were significantly lower than the norm. There was a significant IQ drop in all diagnostic groups. IQ drop, but not current IQ, correlated with duration of rooflessness. Those with schizophrenia or alcohol problems were roofless for longest. Alcohol misuse did not correlate with IQ drop, excepting alcohol withdrawal symptoms in those with schizophrenia. CONCLUSION: The hypothesis that low IQ is a risk factor for rooflessness is supported. However, length of rooflessness was more closely related to IQ drop than to current IQ, suggesting that some third factor may be affecting both rooflessness and intellectual functioning. Roofless men with schizophrenia or alcohol problems may be especially at risk of long-term rooflessness.

Adult↗
PubMed1996

Drug strategies and treatment-resistant schizophrenia.

OBJECTIVES: The aims of the paper are to review the notion of treatment resistance in schizophrenia and consider the factors important in determining non-responsiveness to standard neuroleptic treatment, and to review the strategies currently available in the treatment of such patients, including an evaluation of recently-introduced, novel drug treatments. METHOD: A selective review of the literature relating to treatment resistance was undertaken using medline searches, followed by cross-checking for further articles identified in these references. RESULTS: The various treatment approaches available are considered, including adjunctive treatment with lithium or carbamazepine. The risks and benefits of high dose antipsychotic treatment are discussed. The possible benefits and side-effects of new treatments, particularly the atypical neuroleptics, are also reviewed. CONCLUSIONS: The reasons why a proportion of patients with schizophrenia fail to respond to standard neuroleptic treatment are ill-understood. Nevertheless, initial assessment should include identification of any factors that may be related to a patient's poor response, such as poor compliance, substance use or epilepsy. This may help to determine an appropriate treatment strategy. There is a need to be systematic and to ensure that patients be given an adequate trial of each treatment tested in terms of duration and dosage. The available evidence does not support the use of high doses of neuroleptics for the majority of patients. Adjunctive treatments, such as lithium, carbamazepine or benzodiazepines may be beneficial in non-responsive patients, particularly if certain target symptoms are present. Atypical neuroleptics, particularly clozapine, have proved particularly effective in non-responsive patients as well as those sensitive to the motor side-effects of standard drugs. However, the high risk of agranulocytosis with clozapine is a problem; also the drug and the necessary haematological monitoring are expensive. There are hints that some of the other, new, atypical neuroleptics have some benefit in non-responsive patients, but controlled studies are required.

Antipsychotic Agents↗