Atypical antipsychotic drugs and organization of long-term semantic memory: multidimensional scaling and cluster analyses of category fluency performance in schizophrenia

Organization of semantic memory, one of the domains of cognitive function, is impaired in patients with schizophrenia, and is predictive of functional outcomes. The Category Fluency Task (CFT) has been used to evaluate organization of long-term semantic memory by means of visualizing semantic associations in the form of 'cognitive map' and cluster structures. While atypical antipsychotic drugs (AAPDs) have been shown to ameliorate overall cognitive deficits, little is known about the efficacy of AAPDs for improving higher cognitive functions, such as semantic memory organization. The purpose of the present study was to determine if treatment with olanzapine or ziprasidone has beneficial influence on organization of semantic memory, as revealed by analysis of data from the CFT, in patients with schizophrenia. A retrospective analysis of an open-label trial was conducted for 33 patients with schizophrenia who were treated with either olanzapine or ziprasidone. Nineteen subjects were unmedicated at baseline. The CFT and Letter Fluency Task, as well as the Brief Psychiatric Rating Scale (BPRS) and Quality of Life Scale (QLS), were administered at baseline and 6 wk of the treatment. Semantic structures were obtained by multidimensional scaling analysis and hierarchical cluster analysis of verbal outputs from the CFT. At baseline, no meaningful dimension or cluster was observed in the semantic structure; however, knowledge-based dimensions (wild vs. domestic) appeared after treatment with olanzapine or ziprasidone. Cluster structures also became organized, especially after treatment with olanzapine. Scores of QLS, but not those of BPRS, improved during treatment with the AAPDs. These results suggest a facilitative influence of AAPDs on higher cognitive functions, such as organization of semantic memory, in patients with schizophrenia.