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Neuropsychological change after 6weeks of clozapine treatment was examined in 18 treatment-refractory patients to test anticipated domain-specific cognitive improvements. The first aim of this study was to test the assumption that increased homogeneity of sample and treatment would yield an experimental design with sufficient sensitivity to detect general intellectual changes with clozapine that were not apparent in one previous investigation. The second aim was to test predictions derived from a domain-specific review of all other investigations with clozapine suggesting salient gains on tests sensitive to motor and mental speed, visual spatial manipulation, and new learning of verbal material. The results showed that the comprehensive neuropsychological test battery was sensitive to general cognitive changes with clozapine, and supported the hypothesized domain-specific gains on tests of motor and mental speed, visual spatial manipulation and new verbal learning. Novel gains were also apparent on tests of new learning with nonverbal material. The results are discussed in relation to aspects of experimental design necessary for the evaluation of prospective medication-induced changes in cognitive skill, particularly in future investigations designed to differentiate between second-generation antipsychotic medications.

Uni-rhinal olfactory acuity in schizophrenia was investigated in two experiments. The first assessed the presence of a predicted atypical asymmetry of nostril laterality and the second assessed the effect of antipsychotic treatment on the asymmetry. Although olfactory identification impairment has been well documented in schizophrenia, olfactory acuity has been neglected. This may be an oversight as cerebral structures of the mesial temporal lobe important to olfactory perception have often been implicated in the pathophysiology of schizophrenia and it is thus reasonable to postulate a primary impairment of olfactory acuity in schizophrenia. In addition, unmedicated patients with schizophrenia have exhibited asymmetrical laterality favouring the right over the left hemisphere in studies of visual, haptic, and auditory perception, and the few published prospective treatment studies have suggested a reversal of this asymmetry with first generation neuroleptic treatments. In experiment 1 a generalization of the perceptual asymmetry to olfactory acuity was examined by measurement of n-butanol olfactory thresholds with the Connecticut Chemosensory Perception Exam (CCPE) in an unmedicated sample of 17 patients with schizophrenia and 17 age, gender, and handedness matched normal controls. The patient sample showed an asymmetrical impairment of the left nostril that was not apparent in the normal control sample. In experiment 2, the CCPE was administered to a new sample of 10 patients with schizophrenia before and after neuroleptic treatment. The asymmetry observed in experiment 1 was replicated, and the relative advantage of the right nostril shifted to a relative advantage of the left nostril over the course of 8weeks of treatment. Results are discussed in relation to cerebral aspects of schizophrenia and potential implications to cognitive change from treatment.

The syndrome of schizophrenia often includes negative symptoms and severe cognitive deficits that are resistant to change with conventional pharmacotherapy. The efficacy of clozapine in the reduction of the negative syndrome has prompted a series of studies implicating circumscribed cognitive improvements. Restrictions on the use of clozapine have encouraged the development and introduction of novel compounds with a clinical efficacy profile similar to clozapine that are hoped also to have beneficial cognitive effects. The present review summarizes studies of the cognitive efficacy of novel antipsychotic medications, particularly in regard to issues in experiment design and study implementation that might facilitate additional research. Although preliminary support exists for relatively circumscribed improvement of cognitive status with the use of clozapine and risperidone--and more general improvement with the use of olanzapine--specific inferences relating cognitive change to particular treatments will remain speculative until more sophisticated investigations are completed. The present review emphasises the most relevant design limitations in past studies to provide practical suggestions for the implementation of subsequent investigations Previous results have established the possibility of a medication-based change in cognitive status in schizophrenia Future research will determine the validity of these changes, the cerebral mechanism involved, and their significance to improved prognosis.