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Biomedical subjects

T R Barnes

Publications and source records attributed to T R Barnes.

At least 19 recordsLinked to original sources

Benzodiazepines for neuroleptic-induced acute akathisia.

BACKGROUND: Neuroleptic-induced akathisia is one of the most common and distressing early-onset adverse effects of antipsychotic drugs, being associated with poor compliance with treatment, and thus, ultimately, to an increase risk of relapse. This review assesses the role of benzodiazepines in the pharmacological treatment of this problem. OBJECTIVES: To determine the effects of benzodiazepines versus placebo for people with neuroleptic-induced acute akathisia. SEARCH STRATEGY: Biological Abstracts (January 1982-March 1999), The Cochrane Library (Issue 3 1999), The Cochrane Schizophrenia Group's Register (May 2001), EMBASE (January 1980-March 1999), LILACS (January 1982-March 1999), MEDLINE (January 1964-March 1999), PsycLIT (January 1974-March 1999), and SCISEARCH were searched. Further references were sought from published trials and their authors. SELECTION CRITERIA: All randomised clinical trials comparing benzodiazepines with placebo for people with antipsychotic-induced acute akathisia. DATA COLLECTION AND ANALYSIS: Two reviewers, working independently, selected, quality assessed and extracted data. These data were then analysed on an intention-to-treat basis. For homogeneous dichotomous data the fixed effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences. MAIN RESULTS: Two small (total N=27) randomised controlled trials were included. By seven to 14 days, there was a reduction in symptoms for those patients receiving clonazepam compared with placebo (2 RCTs, N=26, RR 0.09 CI 0.01 to 0.6, NNT 1.2 CI 0.9 to 1.5). No significant difference was found for adverse events (2 RCTs, N=26, RR 3.00 CI 0.2 to 62) or the need for anticholinergic medication (2 RCTs, N=26, RR 1.56 CI 0.9 to 2.7). No one left the two studies early. Data on mental, social and family outcomes could not be pooled and there was little or no data on user satisfaction, deaths, violence, criminal behaviour and costs. REVIEWER'S CONCLUSIONS: Over a short follow-up period, the use of benzodiazepines may reduce the symptoms of antipsychotic-induced acute akathisia. This review highlights the need for well designed, conducted and reported clinical trials to address the claims of open studies.

Acute Disease↗

Anticholinergics for neuroleptic-induced acute akathisia.

BACKGROUND: Neuroleptic-induced akathisia is one of the most common and distressing early-onset adverse effects of conventional antipsychotic drugs, being associated with poor compliance with treatment, and thus, ultimately, with an increased risk of relapse. This review assesses the role of anticholinergic drugs as an adjunct to standard antipsychotic medication in the pharmacological treatment of this problem. OBJECTIVES: To determine the clinical effects of anticholinergic drugs for neuroleptic-induced acute akathisia. SEARCH STRATEGY: The reviewers undertook electronic searches of Biological Abstracts (1982-1999), CINAHL (1982-1999), Cochrane Library (Issue 4 1999), Cochrane Schizophrenia Group's Register (October 1999), EMBASE (1980-1999), LILACS (1982-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified studies were inspected for more trials and first authors contacted. Each included study was sought as a citation on the Science Citation Index database. SELECTION CRITERIA: All randomised clinical trials of anticholinergic drugs versus placebo for people with neuroleptic-induced acute akathisia. DATA COLLECTION AND ANALYSIS: Two reviewers, working independently, selected, quality assessed and extracted data. These data were then analysed on an intention-to-treat basis. For homogeneous dichotomous data the fixed effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences. MAIN RESULTS: No randomised controlled trials could be included. REVIEWER'S CONCLUSIONS: At present, there is no reliable evidence to support or refute the use of anticholinergics for people suffering from neuroleptic-induced acute akathisia. Akathisia is a most distressing movement disorder that remains highly prevalent, both in the developed and developing world. This review highlights the need for well designed, conducted and reported clinical trials to address the claims of open studies as regards the effects of the anticholinergic group of drugs for akathisia.

Akathisia, Drug-Induced↗

A serial longitudinal quantitative MRI study of cerebral changes in first-episode schizophrenia using image segmentation and subvoxel registration.

Lateral ventricular enlargement is the most consistently replicated brain abnormality found in schizophrenia. This article reports a first episode, longitudinal study of ventricular volume using high-resolution serial magnetic resonance imaging (MRI) and recently developed techniques for image registration and quantitation. Baseline and follow-up (on average 8 months later) MRI scans were carried out on 24 patients and 12 controls. Accurate subvoxel registration was performed and subtraction images were produced to reveal areas of regional brain change. Whereas there were no differences between patients and controls with respect to the mean change in ventricular volume, the patients were much more variable in this respect and showed larger increases and decreases. The percentage increase in ventricular size was greater than one standard deviation of control values for 14 patients and the percentage decrease exceeded one standard deviation in eight patients. Although the finding of progressive ventricular enlargement in a proportion of patients supports other studies indicating an ongoing neuropathological process in the early stages of schizophrenia, the reduction of ventricular size in the remaining patients is more difficult to explain. It is suggested that this may reflect improvement in nutrition and hydration following treatment.

Adult↗

Short and long term effects of antipsychotic medication on smooth pursuit eye tracking in schizophrenia.

RATIONALE: Smooth pursuit abnormalities have been observed in antipsychotic naive first-episode patients, suggesting that they are intrinsic to the illness. However, it is not clear whether these abnormalities are as severe as those observed in more chronic patients. In addition, although research suggests that there are no short-term effects of conventional antipsychotic medication, the effects of long-term antipsychotic medication on smooth pursuit eye movements are relatively unknown. OBJECTIVES: To determine the short and long term effects of antipsychotic medication on the smooth pursuit performance of first-episode and chronic patients with schizophrenia. METHODS: We compared the smooth pursuit performance of antipsychotic-treated and untreated first-episode and chronic schizophrenic patients with healthy controls using a comprehensive range of performance measures. This included velocity gain, the number, type and size of intrusive and corrective saccades, and the average time between the change in direction of the target and the change in direction of the eye movement, a measure of subjects' ability to predict target movement. RESULTS: Chronic schizophrenic patients had significantly reduced velocity gain, took longer to respond to the change in target direction and made more catch-up saccades than both first-episode schizophrenic patients and controls. First-episode patients were impaired relative to controls only on the measure of velocity gain. There were no differences between antipsychotic-naive and treated first-episode patients. Antipsychotic-free chronic patients were significantly less impaired on velocity gain than matched continuously treated chronic patients. These results were not influenced by group differences in age and symptom severity. CONCLUSIONS: These results show that: 1) the main index of smooth pursuit, velocity gain, is impaired early in the course of schizophrenia; 2) whereas velocity gain is unaffected by short-term (weeks) medication, it is worsened by chronic (years) treatment; 3) other indices of smooth pursuit, catch-up saccades and ability to predict target movement, are adversely influenced by illness chronicity rather than medication.

Adult↗

Spatial working memory deficits in schizophrenia: relationship with tardive dyskinesia and negative symptoms.

OBJECTIVE: This study examined the interrelationship between negative symptoms, orofacial tardive dyskinesia, and specific neurocognitive processes, particularly those involved in memory and executive function, in patients with schizophrenia. METHOD: A set of computerized neurocognitive tasks, the Cambridge Neuropsychological Test Automated Battery, was used to assess executive and memory function in 54 hospitalized patients with chronic schizophrenia. Analysis of covariance was used to examine differences between groups with or without the topographical syndromes of orofacial tardive dyskinesia and between groups with high or low negative symptom scores. Principal-components and path analyses were used to examine further the influence of negative symptoms and orofacial tardive dyskinesia on performance on tests of memory and executive function. RESULTS: Both orofacial tardive dyskinesia and negative symptoms were significantly and independently associated with deficits on measures of spatial working memory span derived from principal-components analysis, but only orofacial tardive dyskinesia was associated with deficits on measures of spatial working memory strategy. Both were also associated with impairment on the delayed-matching-to-sample task, a test of memory. These associations were not explained by deficits in global intellectual function. Path analysis suggested that the relationships between the clinical symptoms and performance on the delayed-matching-to-sample task were mediated entirely through their relationship with the spatial working memory measures. CONCLUSIONS: In schizophrenia, orofacial tardive dyskinesia and evident negative symptoms are relatively independent markers of compromise of the cerebral systems that mediate spatial working memory. Candidate neural circuits include the frontal-striatal-thalamic systems, particularly those involving the dorsolateral prefrontal cortex.

Adult↗

Comorbid non-alcohol substance misuse among people with schizophrenia: epidemiological study in central London.

BACKGROUND: Few epidemiological studies have assessed the extent and nature of comorbid non-alcohol substance misuse in people with schizophrenia in the community in the UK. AIMS: To study the extent and nature of comorbid non-alcohol substance misuse in people with schizophrenia in central London. METHOD: Subjects were identified in an epidemiological census survey of South Westminster. Standardised assessment of each subject included demographic data, ratings of mental state and movement disorder and questioning about drug and alcohol misuse. RESULTS: Individuals with schizophrenia or related psychoses were identified (n=352) and 57 (16%) reported a lifetime history of non-alcohol substance misuse. Age and gender were the main variables relevant to the extent and pattern of misuse. Self-reported non-alcohol substance misuse showed no significant relationship with a range of outcome measures. CONCLUSIONS: The high proportion of subjects reporting non-alcohol substance misuse is comparable with figures from the USA. The reports of lifetime misuse most commonly referred to cannabis, psychostimulants, LSD, opiates and anticholinergics. Misuse was concentrated in those younger than 36 years and was reported more often by males.

Adolescent↗

Saccadic hypometria in drug-naive and drug-treated schizophrenic patients: a working memory deficit?

In certain conditions patients with schizophrenia make markedly smaller (hypometric) saccades than controls. This hypometria has been thought to reflect dopaminergic blockade as a result of antipsychotic medication. We tested this hypothesis by comparing the performance of an antipsychotic-naïve group and an antipsychotic-treated group of first-episode schizophrenic patients on a predictive saccade paradigm. We explored the possibility that hypometria reflects a spatial working memory deficit by correlating performance on neuropsychological tests of mnemonic function with saccadic accuracy. Both the drug-naïve and treated schizophrenic patients made hypometric saccades when compared with a group of matched controls. Primary saccade amplitude also correlated significantly with performance on some of the neuropsychological tests. These results are discussed in terms of the roles of cortical dopamine and working memory deficits in schizophrenic patients.

Adult↗

A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication.

BACKGROUND: Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia. Although the cumulative evidence is strong, early controlled trials showed methodological limitations. METHODS: A randomized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention. Both interventions were delivered by 2 experienced nurses who received regular supervision. Patients were assessed by blind raters at baseline, after treatment (lasting up to 9 months), and at a 9-month follow-up evaluation. Patients continued to receive routine care throughout the study. An assessor blind to the patients' treatment groups rated the technical quality of audiotaped sessions chosen at random. Analysis was by intention to treat. RESULTS: Ninety patients received a mean of 19 individual treatment sessions over 9 months, with no significant between-group differences in treatment duration. Both interventions resulted in significant reductions in positive and negative symptoms and depression. At the 9-month follow-up evaluation, patients who had received cognitive therapy continued to improve, while those in the befriending group did not. These results were not attributable to changes in prescribed medication. CONCLUSION: Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to standard antipsychotic drugs, with its efficacy sustained over 9 months of follow-up.

Adult↗

Smooth pursuit eye tracking over a structured background in first-episode schizophrenic patients.

Whilst most laboratory smooth pursuit tasks are performed in the dark, in everyday life pursuit commonly occurs over a structured background. This background provides a powerful stimulus to the optokinetic reflex (OKR), inducing a background "drag" on pursuit eye movements. An inability to inhibit the influence of the OKR may be a contributing factor to the dysfunctional pursuit performance observed in many schizophrenic patients. Smooth pursuit performance was measured in 23 first-episode schizophrenic patients and 23 healthy controls matched for age and estimated IQ, both in the dark and over a structured background (a random checkerboard of black and white squares). Velocity gain was measured, as well as the number and size of corrective saccades (catch-up saccades) and intrusive saccades (anticipatory saccades and square wave jerks). Overall, schizophrenic patients had lower velocity gain and made more catch-up saccades than controls. The effect of the background was to lower velocity gain and increase the number of catch-up saccades to the same extent in schizophrenic patients and controls. There were no significant interactions between group and background effect. These results suggest that, although their overall level of performance was worse, the schizophrenic patients were as able as controls to inhibit the effect of the OKR. Since lesion studies show that inhibition of the OKR requires intact inferior parietal regions in man (Lawden et al., 1995), one hypothesis is that the parietal component of smooth pursuit may be intact in schizophrenia.

Adult↗

Actigraphic monitoring (actigraphy) of circadian locomotor activity in schizophrenic patients with acute neuroleptic-induced akathisia.

BACKGROUND: Actigraphy is a quantitative method for measurement of motor activity. In the present study we used actigraphy to examine diurnal variations in locomotor activity of schizophrenic patients with neuroleptic-induced akathisia (NIA). METHOD: Thirty-two schizophrenic patients, 16 with NIA and 16 without (DSM-IV criteria) underwent 24-h actigraphic monitoring. Clinical assessments of NIA were conducted with Barnes Akathisia Scale (BAS) at 08:00, 12:00, 16:00 and 20:00. Sleep parameters (duration, latency, continuity and efficacy) were assessed by actigraphy. Sleep quality was evaluated by a self-rated sleep questionnaire. RESULTS: NIA patients demonstrated persistent higher daytime motor activity from 11:30 to 14:15 and from 18:00 to 21:00 than controls. There were no differences between the groups in nighttime motor activity, confirming clinical observations that NIA tends to disappear during sleep. Subject's sleep assessments were similar in the two groups. CONCLUSIONS: Actigraphy seems to be a reliable, non-invasive, method of measuring motor activity in patients with NIA. Its sensitivity and specificity as an objective quantitative diagnostic instrument in patients with NIA merits further investigation.

Adult↗

Clinical correlates of akathisia in acute psychiatric inpatients.

This study identified acute and chronic akathisia in acute psychiatric inpatients receiving conventional antipsychotic medication, and evaluated the clinical characteristics, risk factors and clinical implications of the condition. Akathisia and other movement disorders were systematically assessed in patients consecutively admitted to an acute psychiatric ward over one year. Akathisia was diagnosed in 15 (21%) of 72 patients. Akathisia, developing as an acute condition in seven patients, generally presented with the subjective experience of dysphoria and unease without restless movements. This acute akathisia developed during the first few days of hospitalization and was associated with both a higher average dose of antipsychotic medication and a greater increase in dosage. In the remaining eight cases, akathisia was already present on admission, and thus classified as chronic. Those patients with chronic akathisia exhibited both subjective restlessness and the characteristic restless movements. Chronic akathisia was unrelated to antipsychotic dosage. The proportion of patients with akathisia who discontinued drug treatment was significantly higher than that for patients without the condition. Patients with acute akathisia tended to drop-out of treatment and those with the chronic form tended to have treatment withdrawn by the prescribing clinician. One interpretation is that the subjective distress of acute akathisia may be particularly difficult for patients to tolerate and leads them to stop medication, while patients with more chronic akathisia may have become more accepting of the experience. Repetitive movements of the legs were observed more commonly in those with chronic rather than acute akathisia, and may represent a way of achieving some limited respite.

Adult↗

West London first-episode study of schizophrenia. Clinical correlates of duration of untreated psychosis.

BACKGROUND: Studies in schizophrenia suggest that a longer initial period of untreated illness is associated with a poorer clinical outcome. AIMS: To determine whether, in first-episode schizophrenia, a longer duration of untreated psychosis (DUP) or of untreated illness (DUI) (DUP plus any prodrome) is associated with clinical variables that could mediate a poor prognosis. METHOD: Clinical, social, neuropsychological and oculomotor function data on 53 patients with first-episode schizophrenia were related to the DUP and DUI. RESULTS: Comparing short and long DUP groups split around the median showed no statistically significant differences (except age); patients in the latter group tended to perform worse on an executive attentional set-shifting task, and were more likely to be unemployed, and living alone or homeless. CONCLUSIONS: There was little evidence of any association between either DUP or DUI and progressive deterioration in the schizophrenic illness or the development of resistance to initial drug treatment. Social variables that augur a poor prognosis may be associated with delayed presentation of schizophrenia to psychiatric services.

Adult↗

Comparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage.

Neuropsychological studies of patients with schizophrenia have consistently identified deficits on tests sensitive to frontal lobe function. One paradigm that has been widely used is that of attentional set-shifting using the Wisconsin Card Sorting Test (WCST). In the present study, patients with chronic schizophrenia and with frontal lobe lesions were assessed on a computerised set-shifting task that provides a componential analysis of the WCST by distinguishing between intra-dimensional and extra-dimensional set-shifting. Out of 51 patients with schizophrenia, those with high IQ (n =24) were compared with patients with lesions in prefrontal cortex (n = 22) and with normal control subjects (n= 18). These three groups were well matched for age, sex and National Adult Reading Test (NART) IQ. The schizophrenic group showed a significantly higher rate of attrition at the intra-dimensional shift stage of learning compared with the other two groups. At the extra-dimensional shift stage, both the schizophrenic and frontal lesioned groups showed greater attrition than controls. Further, patients with schizophrenia who were able to learn the intradimensional reversal stage required more trials and made significantly more errors at that stage than the other two groups. In comparison with high IQ patients with schizophrenia, those with low IQ performed at a lower level but showed a qualitatively similar pattern of performance, providing further evidence that the set-shifting deficits were not simply explained by any global intellectual decline. Patients with schizophrenia who dropped out at the extradimensional shift stage had higher negative symptom scores compared with patients dropping out at previous learning stages, while patients failing at the intra-dimensional shift stage had lower scores for bradyphrenia (slowness of thought). The results suggest that patients with chronic schizophrenia fail to 'learn set' and are impaired at both set-shifting and concept formation. The relevance of these findings to understanding the nature of prefrontal cortical deficits in chronic schizophrenia is discussed. The implication of these findings to the rehabilitation of these patients is considered.

Adult↗

Four behavioural syndromes of schizophrenia: a replication in a second inner-London epidemiological sample.

In a previous large epidemiological survey of patients with strictly defined schizophrenia in the London borough of Camden, we extracted four behavioural syndromes (Social withdrawal, Thought disturbance, Anti-social behaviour and Depressed behaviour) by factor analysis of MRC Social Behaviour Schedule (SBS) data. These syndromes had significant differential relationships to symptoms assessed using the Manchester Scale (MS), symptom-derived syndromes, and social functioning variables. A second inner-London epidemiological survey of schizophrenia in South Westminster using identical methodology found the same four behavioural syndromes with identical core component items. The same four behavioural syndromes were extracted, whether applying strict Feighner diagnostic criteria (n=112) or broader DSM-III-R criteria (n=198). The four syndromes extracted from the Feighner positive sample showed relationships to symptoms and social functioning variables similar to those found in the original Camden study. However, the symptom-derived factors were not the same and did not conform to the three recognised symptom-based syndromes of schizophrenia. This successful replication suggests that assessment of the four behavioural syndromes of schizophrenia offers a different perspective on disability and a potentially relevant measure in clinical practice, clinical trials and studies of the neuropsychology and pathophysiology of schizophrenia.

Adult↗

Spontaneous dyskinesia in first episode schizophrenia.

In the west London prospective study of first episode schizophrenia, the prevalence and nature of abnormal involuntary movements were examined in 27 patients who had never received antipsychotic drugs and 36 who had been treated with such medication. Motor disturbance was assessed with rating scales designed to cover the full range of spontaneous and drug induced movement disorder. Only one person in the drug naive group showed evidence ofparkinsonism, a finding which contrasts with recent reports suggesting that spontaneous extrapyramidal signs may not be uncommon in such patients. However, according to ratings on the modified Rogers scale, 11% of the drug naive group exhibited orofacial dyskinesia, 4% trunk and limb dyskinesia, 7% postural abnormalities, and 4% increased muscle tone. The respective figures in the closely matched medicated group were not significantly different except for increased muscle tone, which was significantly more common (25%). The proportion of drug naive patients fulfilling criteria for tardive dyskinesia on the abnormal involuntary movements scale ranged from 4% to 11% depending on the criterion threshold score used. These findings are in accord with the notion that abnormal involuntary movements, particularly orofacial dyskinesia, represent a neuromotor component of schizophrenia.

Adolescent↗

Executive function in first-episode schizophrenia.

BACKGROUND: We tested the hypothesis that schizophrenia is primarily a frontostriatal disorder by examining executive function in first-episode patients. Previous studies have shown either equal decrements in many cognitive domains or specific deficits in memory. Such studies have grouped test results or have used few executive measures, thus, possibly losing information. We, therefore, measured a range of executive ability with tests known to be sensitive to frontal lobe function. METHODS: Thirty first-episode schizophrenic patients and 30 normal volunteers, matched for age and NART IQ, were tested on computerized test of planning, spatial working memory and attentional set shifting from the Cambridge Automated Neuropsychological Test Battery. Computerized and traditional tests of memory were also administered for comparison. RESULTS: Patients were worse on all tests but the profile was non-uniform. A componential analysis indicated that the patients were characterized by a poor ability to think ahead and organize responses but an intact ability to switch attention and inhibit prepotent responses. Patients also demonstrated poor memory, especially for free recall of a story and associate learning of unrelated word pairs. CONCLUSIONS: In contradistinction to previous studies, schizophrenic patients do have profound executive impairments at the beginning of the illness. However, these concern planning and strategy use rather than attentional set shifting, which is generally unimpaired. Previous findings in more chronic patients, of severe attentional set shifting impairment, suggest that executive cognitive deficits are progressive during the course of schizophrenia. The finding of severe mnemonic impairment at first episode suggests that cognitive deficits are not restricted to one cognitive domain.

Adolescent↗

Smooth pursuit and saccadic abnormalities in first-episode schizophrenia.

BACKGROUND: Previous studies of oculomotor dysfunction in schizophrenia have tended to concentrate on abnormalities of smooth pursuit eye tracking in chronic medicated patients. We report the results of a study of smooth pursuit, reflexive and antisaccade performance in drug naive and antipsychotic treated first-episode schizophrenic patients. METHODS: Smooth pursuit and saccadic eye movements were recorded in 36 first-episode schizophrenic patients and 36 controls matched for age and estimated IQ. The schizophrenic patients were divided into drug-naive (N = 17) and antipsychotic treated groups (N = 19). RESULTS: Smooth pursuit velocity gain was significantly lower than controls only in the drug-naive patients. The treated patients did not differ significantly from either the controls or the untreated group. In an antisaccade paradigm both treated and drug-naive schizophrenic patients demonstrated an increased number of errors, but only drug-naive patients also demonstrated an increased latency in initiating correct antisaccades. CONCLUSIONS: These impairments are unlikely to be due to a generalized deficit in oculomotor function in the schizophrenic groups, as there were no differences between the groups in saccadic metrics on a reflexive saccade task. The results show that both smooth pursuit and saccadic abnormalities are present at the onset of schizophrenia and are integral to the disorder.

Adolescent↗