Samuel B. Hutton

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.

Discrimination Learning, Reversal, and Set-Shifting in First-Episode Schizophrenia: Stability Over Six Years and Specific Associations with Medication Type and Disorganization Syndrome

Background The intradimensional/extradimensional (IDED) task assesses different forms of learning from feedback. Limited evidence suggests that attentional set-shifting deteriorates over time in schizophrenia. We tested this hypothesis and examined the specificity of learning impairments identified by this task. Method Two hundred sixty-two first-episode patients and 76 healthy control subjects, matched for age and premorbid IQ, were tested; 104 patients and 25 control subjects were reassessed 1 and 3 years later, and 31 patients were reassessed additionally 6 years later. Results Patients showed impaired set-shifting that correlated with current IQ and working memory, but there were no impairments when subgroups were matched on current IQ. In contrast, patients showed marked impairments in rule reversal learning that survived correction for IQ, were present in the context of intact rule abstraction, and correlated with disorganization symptoms. Patients prescribed second-generation antipsychotics were worse on set-shifting compared with first-generation, a finding not explained by demographic data, illness characteristics, or IQ. Patients and control subjects showed stable IDED performance over the first 6 years of illness, although set-shifting was inconsistent over the first year. Those with residual negative symptoms were more likely to fail the set-shifting stage at follow-up. Conclusions First-episode schizophrenia patients can learn and generalize rules but are inflexible when rules change, reflecting reduced responsiveness to negative feedback and difficulty in switching attention. Rule-reversal is a promising target for translational studies, because it is specific, clinically relevant, and might reflect orbitofrontal dysfunction. Set-shifting is related to poor function more generally but might be sensitive to medication effects and valuable for clinical trials.

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

Objective:  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.

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.

Duration of untreated psychosis and social function: 1-year follow-up study of first-episode schizophrenia

Background In first-episode schizophrenia, longer duration of untreated psychosis (DUP) predicts poorer outcomes. Aims To address whether the relationship between DUP and outcome is a direct causal one or the result of association between symptoms and/or cognitive functioning and social functioning at the same time point. Method Symptoms, social function and cognitive function were assessed in 98 patients with first-episode schizphrenia at presentation and 1 year later. Results There was no significant clinical difference between participants with short and long DUP at presentation. Linear regression analyses revealed that longer DUP significantly predicted more severe positive and negative symptoms and poorer social function at 1 year, independent of scores at presentation. Path analyses revealed independent direct relationships between DUP and social function, core negative symptoms and positive symptoms. There was no significant association between DUP and cognition. Conclusions Longer DUP predicts poor social function independently of symptoms. The findings underline the importance of taking account of the phenomenological overlap between measures of negative symptoms and social function when investigating the effects of DUP.

IQ as a predictor of functional outcome in schizophrenia: a longitudinal, four-year study of first-episode psychosis.

Studies of established schizophrenia have consistently found that cognitive function predicts social and clinical outcomes. The findings from first-episode studies have been more variable, with only some studies reporting predictive relationships. We tested the possibility that an index of general cognitive ability, IQ, may be a more sensitive and reliable predictor of outcome in first-episode schizophrenia than specific measures of memory and executive function. Fifty-four patients with first-episode schizophrenia or schizoaffective disorder were assessed for cognitive and social function as well as symptoms at three time points over the four years following first presentation of their psychotic illness. Regression analyses were performed to determine whether IQ and specific neuropsychological measures at first episode and one-year follow-up predicted four-year social function and residual symptoms. The effects of premorbid and concurrent IQ on outcome were also assessed. Premorbid IQ and IQ at each assessment significantly predicted social function at four-year follow-up. This relationship remained significant after the social function or symptom scores at first presentation were accounted for in the regression. Specific measures predicted certain domains of social function, but these were weaker and less consistent than IQ. The predictive values of cognition on residual symptoms were less strong; the most consistent finding was a relationship between IQ and the negative syndrome. This study suggests that early in the course of schizophrenia, general cognitive ability, as measured by IQ, is a more sensitive and reliable predictor of functional outcome than measures of specific ability.

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

BACKGROUND Both 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. METHODS We 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. RESULTS Antisaccade 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. CONCLUSIONS These 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.

Sex differences in scanning faces: Does attention to the eyes explain female superiority in facial expression recognition?

Previous meta-analyses support a female advantage in decoding non-verbal emotion (Hall, 1978, 1984), yet the mechanisms underlying this advantage are not understood. The present study examined whether the female advantage is related to greater female attention to the eyes. Eye-tracking techniques were used to measure attention to the eyes in 19 males and 20 females during a facial expression recognition task. Women were faster and more accurate in their expression recognition compared with men, and women looked more at the eyes than men. Positive relationships were observed between dwell time and number of fixations to the eyes and both accuracy of facial expression recognition and speed of facial expression recognition. These results support the hypothesis that the female advantage in facial expression recognition is related to greater female attention to the eyes.

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.