Em Joyce

Executive function in first-episode schizophrenia

BACKGROUNDnWe 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.nnnMETHODSnThirty 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.nnnRESULTSnPatients 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.nnnCONCLUSIONSnIn 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.

Clinical correlates of early medication adherence: West London first episode schizophrenia study

Objective:u2002 Little is known about factors that mediate adherence with medication during the early stages of antipsychotic treatment in schizophrenia. This study sought to identify factors that may be associated with medication adherence in first‐episode schizophrenia.

Smooth pursuit and saccadic abnormalities in first-episode schizophrenia.

BACKGROUNDnPrevious 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.nnnMETHODSnSmooth 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).nnnRESULTSnSmooth 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.nnnCONCLUSIONSnThese 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.

The relationship between antisaccades, smooth pursuit, and executive dysfunction in first-episode schizophrenia

BACKGROUNDnBoth oculomotor and neuropsychologic deficits have been used to support the hypothesis that schizophrenia is associated with prefrontal cortex dysfunction, but studies that have specifically investigated the relationships between these deficits have produced inconsistent findings.nnnMETHODSnWe measured both smooth pursuit and antisaccade performance in a large group (n = 109) of patients with first-episode schizophrenia and a group of matched control subjects (n = 59) and investigated the relationship between performance on these tasks and performance on a range of executive tasks. We additionally explored the relationship between these variables and measures of psychopathology at presentation and duration of untreated psychosis.nnnRESULTSnAntisaccade errors were significantly correlated with spatial working memory performance. Smooth pursuit gain did not correlate with any neuropsychologic measure. There were no reliable correlations between either oculomotor variables and measures of psychopathology and duration of untreated psychosis.nnnCONCLUSIONSnThese findings suggest that in schizophrenia working memory and antisaccade performance reflect the same abnormal prefrontal substrates and that smooth pursuit is mediated by a separate neural abnormality.

Relationship between insight, cognitive function, social function and symptomatology in schizophrenia: the West London first episode study

ObjectiveTo examine the nature and clinical correlates of insight in first-episode schizophrenia, and how these differ from findings in established schizophrenia.MethodInsight (and insight dimensions), clinical symptoms, neurocognitive function and social function were assessed in 94 patients with first-episode schizophrenia or schizophreniform disorder according to DSM-IV criteria.ResultsGreater global insight was associated with more severe depression. Poor overall insight was associated significantly with more severe negative and disorganisation symptoms as well as poor working memory, and at a trend level with lower current IQ. Patients with poor insight perceived themselves to have a better level of independent performance at daily living activities.ConclusionIn first-episode psychosis, the clinical correlates of poor insight are similar to those reported for established schizophrenia. Those patients with greater insight may be at risk of depression. The complex relationships between insight, positive and negative symptoms, neurocognitive dysfunction and social function may reflect the multidimensional nature of insight.

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.

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.

The suitability of actigraphy, diary data, and urinary melatonin profiles for quantitative assessment of sleep disturbances in schizophrenia: A case report

Sleep disruption is a commonly encountered clinical feature in schizophrenic patients, and one important concern is to determine the extent of this disruption under “real” life situations. Simultaneous wrist actigraphy, diary records, and repeated urine collection for urinary 6‐sulphatoxymelatonin (aMT6s) profiles are appropriate tools to assess circadian rhythms and sleep patterns in field studies. Their suitability for long‐term recordings of schizophrenic patients living in the community has not been evaluated. In this case report, we document long‐term simultaneous wrist actigraphy, light detection, repeated urine collection, and diary records as a suitable combination of non‐invasive techniques to quantify and assess changes in sleep‐wake cycles, light exposure, and melatonin profiles in a schizophrenic patient. The actigraph was well‐tolerated by the patient, and compliance to diary records and 48 h urine collection was particularly good with assistance from family members. The data obtained by these techniques are illustrated, and the results reveal remarkable abnormal patterns of rest‐activity patterns, light exposure, and melatonin production. We observed various rest‐activity patterns, including phase‐shifts, highly delayed sleep on‐ and offsets, and irregular rest‐activity phases. The period of the rest‐activity rhythm, light‐dark cycle, and melatonin rhythm was longer than 24 h. These circadian abnormalities may reinforce the altered sleep patterns and the problems of cognitive function and social engagement associated with schizophrenic.

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.

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.