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Biomedical subjects

S B Hutton

Publications and source records attributed to S B Hutton.

12 recordsLinked to original sources

Decision making deficits in patients with first-episode and chronic schizophrenia.

A considerable body of evidence suggests that the dorsolateral prefrontal cortex is dysfunctional in schizophrenia. However, relatively few studies have explored the involvement of other areas of the frontal cortex. Research suggests that the orbitofrontal cortex (OFC) plays an important role in decision making processes. We assessed the decision making cognition of first-episode and chronic schizophrenic patients with a novel task sensitive to orbitofrontal dysfunction. Both first-episode and chronic patients with schizophrenia took longer than matched controls to make decisions, and both groups were also impaired on a measure of risk adjustment. The impairment in these measures was more severe in the chronic patients than in the first-episode patients, and only the chronic patients made significantly fewer optimal decisions than controls. These results contribute to increasing evidence of orbitofrontal dysfunction in schizophrenia, and suggest that disease progression or the effects of long term antipsychotic medication may influence performance on this task.

Analysis of Variance↗

Saccadic distractibility in first-episode schizophrenia.

In the antisaccade paradigm, subjects are instructed to fixate a central point, and then move their eyes towards a position in space in the opposite direction but equidistant to a peripheral, sudden onset target. Antisaccade errors occur when subjects are "distracted" by the target and make a saccade towards it. These errors are more common in patients with schizophrenia but the underlying cause remains unclear. To determine whether antisaccade errors simply reflect a general inability to maintain fixation or are the consequence of a more specific deficit in the strategic control of internally generated actions, patients with first-episode schizophrenia and healthy controls performed three saccadic paradigms which shared the core feature of requiring a prepotent saccade to be suppressed, but varied in their concurrent cognitive demands. We found that both groups showed an increase in errors as the cognitive demands increased across task. However, this increase was significantly steeper in the schizophrenic patients than in the controls. We also found that schizophrenic patients were as able as controls to inhibit prepotent saccades towards a target in a paradigm with no other cognitive demands. Possible explanations of these results include reduced working memory resources and impaired motor preparation in schizophrenia.

Adult↗

Orbitofrontal cortex mediates inhibition of return.

Recent accounts have proposed that orbitofrontal cerebral cortex mediates the control of behavior based on emotional feedback and its somatic correlates. Here, we describe the performance of a patient with circumscribed damage to orbitofrontal cortex during a task that requires switching between sensory-motor mappings, contingent on the occurrence of positive and negative reward feedbacks. In this test, normal subjects and other patients with prefrontal damage show an increase in latencies for eye movements towards locations at which a negative feedback was presented on the preceding trial. In contrast, our patient does not show this reward-dependent inhibition of return effect on saccades. She was also found to make an increased rate of ocular refixations during visual search and used a disorganized search strategy in a token foraging task. These findings suggest that orbital regions of the prefrontal cortex mediate an inhibitory effect on actions directed towards locations that have been subject to negative reinforcement. Further, this mechanism seems to play a role in controlling natural search and foraging behavior.

Adult↗

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↗

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↗

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↗

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↗

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↗