Physostigmine and cognition in schizotypal personality disorder.

There is evidence that reduced cholinergic activity may play a role in the pathophysiology of cognitive impairment in the schizophrenia spectrum. We tested the effects of physostigmine, an anticholinesterase inhibitor, on visuospatial working memory as evaluated by the Dot test, and on verbal learning and recall as measured by a serial learning task in patients with schizotypal personality disorder. Physostigmine tended to improve the Dot test, but not serial verbal learning performance in these patients.

New perspectives on schizotypal personality disorder.

Schizotypal personality disorder is the prototype of the schizophrenia-related personality disorders and has been demonstrated to have phenomenologic, biologic, treatment, and outcome characteristics similar to those of schizophrenic patients. These studies suggest that patients with schizotypal personality disorder, like schizophrenic patients, show cognitive impairment, but the impairment is more focal and involves primarily working memory, verbal learning, and sustained attention rather than generalized intellectual deficits. Schizotypal patients, like schizophrenic patients show reductions in temporal lobe volume, but seem to be spared the frontal volume reductions found in some studies of schizophrenic patients and in our laboratory. Better frontal "buffering" may prevent the more severe cognitive and social deterioration associated with schizophrenia. Furthermore, schizotypal patients appear to show less susceptibility to psychotic symptoms, in part perhaps because of better buffered subcortical dopaminergic activity as suggested by recent data from a SPECT/amphetamine paradigm, glucose metabolic study, and structural studies of basal ganglia. These findings are discussed in terms of a model of schizotypal personality disorder where schizotypal patients have better capacity for compensatory buffering in lateral and subcortical brain regions, protecting them from the more severe symptoms of chronic schizophrenia.

Effects of amphetamine on visuospatial working memory performance in schizophrenia spectrum personality disorder.

Our objective was to determine if amphetamine improves visuospatial working memory, which is impaired in the schizophrenia spectrum and may be modulated by dopamine in prefrontal cortex. To this end, oral amphetamine (30 mg) was administered to 12 patients with schizophrenia spectrum personality disorders and 13 patients with other, nonschizophrenia-related personality disorders. Visuospatial working memory was assessed using the Dot test; a test in which subjects are asked to memorize and reproduce the position of a dot on a sheet of paper. Patients with schizophrenia spectrum personality disorders performed significantly worse than the comparison group in the placebo condition and showed significantly greater improvement after amphetamine, as compared to a nonschizophrenia-related personality disorder comparison group. Patients with greatest impairment at baseline improved most. Amphetamine tended to improve negative symptoms; whereas, positive symptoms remained unchanged. Amphetamine may improve visuospatial working memory in schizophrenia spectrum patients.