Prediction of changes in memory performance by plasma homovanillic acid levels in clozapine-treated patients with schizophrenia.

RATIONALE: Cognitive dysfunction in schizophrenia has been demonstrated to be dependent, in part, on dopaminergic activity. Clozapine has been found to improve some domains of cognition, including verbal memory, in patients with schizophrenia. OBJECTIVES: This study tested the hypothesis that plasma homovanillic acid (pHVA) levels, a peripheral measure of central dopaminergic activity, would predict the change in memory performance in patients with schizophrenia treated with clozapine. METHODS: Twenty-seven male patients with schizophrenia received clozapine treatment for 6 weeks. Verbal list learning (VLL)-Delayed Recall (VLL-DR), a test of secondary verbal memory, was administered before and after clozapine treatment. Blood samples to measure pHVA levels were collected at baseline. RESULTS: Baseline pHVA levels were negatively correlated with change in performance on VLL-DR; the lower baseline pHVA level was associated with greater improvement in performance on VLL-DR during treatment with clozapine. Baseline pHVA levels in subjects who showed improvement in verbal memory during clozapine treatment ( n=13) were significantly lower than those in subjects whose memory performance did not improve ( n=14). CONCLUSIONS: The results of this study indicate that baseline pHVA levels predict the ability of clozapine to improve memory performance in patients with schizophrenia.

Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment.

OBJECTIVE: The goal of this study was to evaluate the effects of the addition of tandospirone, a serotonin-1A (5-HT(1A)) agonist, to ongoing treatment with typical antipsychotic drugs, on two cognitive domains that are relevant to functional outcome in patients with schizophrenia. METHOD: Twenty-six patients with schizophrenia who were receiving stable doses of typical antipsychotics were randomly assigned to adjunctive treatment with 30 mg/day of tandospirone or placebo for 6 weeks. Executive function and verbal memory as well as psychopathology were assessed at baseline and after 6 weeks. RESULTS: Both cognitive measures improved significantly in the patients who received tandospirone; subjects who did not receive tandospirone showed no change. There was no significant change in psychopathology ratings in either group. CONCLUSIONS: The results suggest the usefulness of 5-HT(1A) agonists for enhancing some types of cognitive performance and possibly social and work function in patients with schizophrenia.

The effect of tandospirone, a serotonin(1A) agonist, on memory function in schizophrenia.

BACKGROUND: The purpose of this study was to test the hypothesis that the addition of tandospirone, a 5-HT(1A) partial agonist, to ongoing treatment with typical antipsychotic drugs, would improve memory function in patients with schizophrenia. METHODS: Eleven outpatients (male/female = 7/4) with schizophrenia who had been on stable doses of haloperidol and biperiden were given tandospirone, 30 mg/day, for 4 weeks. The Wechsler Memory Scale-Revised (WMS-R) was administered at baseline and 4 weeks after the addition of tandospirone. The Brief Psychiatric Rating Scale (BPRS; Total, Positive, and Negative subscale scores) and the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) were also completed on the two occasions. To exclude the possibility of a practice effect on the WMS-R test, 11 age-matched patients with schizophrenia (M/F = 7/4) were tested at baseline and after a 4-week interval. RESULTS: Repeated measures analysis of variance revealed a significant time by group (patients with or without tandospirone) effect for the Verbal-, but not the Visual Memory composite scores of the WMS-R test; no significant change was observed in patients without tandospirone, whereas improvement in the Verbal Memory score was noted in patients receiving tandospirone. Moreover, there was improvement in the Inclusion score, an index of memory organization as measured by the Logical Memory subtest of WMS-R, only in patients with tandospirone. Scores on the BPRS and SAS were improved during treatment with tandospirone, but the effects did not reach statistical significance. CONCLUSIONS: The results suggest that adjunctive treatment with 5-HT(1A) agonists may improve some types of memory function in schizophrenia.

Semantic structure in schizophrenia as assessed by the category fluency test: effect of verbal intelligence and age of onset.

It has been reported that long-term memory function, including the semantic structure of category, is impaired in patients with schizophrenia. The present study was performed to determine: (1) whether the deficit in semantic structure in schizophrenia is independent of cultural backgrounds, and (2) the effect of age of onset and verbal intelligence on the degradation of semantic structure in these patients. Fifty-seven Japanese patients with schizophrenia and 33 normal control subjects entered the study. The semantic structure was derived by Multidimensional Scaling (MDS) analysis based on data from the ANIMAL category fluency test. The semantic structure was compared between: (1) schizophrenic patients as a whole vs. normal control subjects; (2) earlier onset (age of onset <20 years) vs. later-onset groups of patients; and (3) high Vocabulary score (score of the Vocabulary subtest from the WAIS-R>7) vs. low Vocabulary score patient groups. Normal control subjects demonstrated the domestic/size dimension in semantic structure, while no such dimension was obtained in patients with schizophrenia. The subgroup comparisons revealed that the later onset or the high Vocabulary score group maintained a relatively intact semantic structure compared with the earlier onset or the low Vocabulary score group, respectively. These findings suggest that the deficit in semantic structure in patients with schizophrenia is commonly observed irrespective of cultural backgrounds, and that age of onset and the level of verbal intelligence are closely related to severity of degradation of the semantic structure in schizophrenia.

[The development of category based induction: five- and six-year-old children's plausibility judgement for general arguments].

The purpose of this study was to investigate preschoolers' ability in judging the plausibility of arguments in Category Based Induction. Experiment 1 was conducted to clarify whether five- and six-year-old children could judge plausibility of general arguments by analyzing the inclusive category of conclusion. The effect of premise typicality, premise diversity, and premise monotonicity of general arguments were examined for this purpose. All the three premise effects were found in six-year-old children, while only the effect of premise monotonicity was found in five-year-old children. In Experiment 2, the effect of premise non-monotonicity was tested to clarify whether children could judge plausibility of arguments by recognizing an inclusion relationship between premise and conclusion categories. The effect of premise non-monotonicity was found in five-year-old children, though it was not perfect. The results of the two experiments suggest that development of Category Based Induction can be divided into two stages. At first, "category based" induction, which means that children can judge plausibility of arguments by recognizing inclusion relationship between premise and conclusion categories, is established from five to six. Later, "category structure based" induction, which means that children can judge plausibility of arguments based on analysis of inclusive category of conclusion, is achieved six and above.

[A choice of domain of judgment in acquisition of universal quantifier expressions].

The present paper examined whether 3-5 year old children can answer correctly to universal quantifier expressions which refer to elements in front of them. In Experiment 1, likely and unlikely situations, manipulated by entity color relation (e.g., likely: red flower, unlikely: black moon), were presented. The result showed that a large number of 4-5 year old children could not affirm the true but unlikely situations. In Experiment 2, the elements which did not have any typical color were used in the likely situations. Children made incorrect judgment equally to both likely and unlikely situations. However, in Experiment 3, those children were able to affirm or negate situations in front of them correctly, if the elements were novel to them. These results indicate that in true-false judgment for universal quantifier expressions, 4-5 year old children tend to base their judgment on their knowledge rather than situations just in front of them. This phenomenon is discussed from the point of view of intellectual realism.

[Velocity perception for curved motion].

This study examined the effect of direction change of tangential velocity on speed perception using a dot in curved motion. The PSE values were measured for four standard stimuli of different motion curvature. In Experiment 1, semicircular motion was a comparison stimulus. The result showed that the PSE values increased with increasing motion curvature. This implies that direction change of tangential velocity can affect its speed perception. However, in Experiment 2, the effect of direction change of tangential velocity was not clear when a comparison stimulus was replaced with linear motion. In Experiment 3, the motion curvature as a comparison stimulus was set near the threshold level of curvature detection. As the result, the similar trend to Experiment 1 was observed. However, the effect of direction change of tangential velocity remained the same as Experiment 2. These results suggests that direction change of tangential velocity can affect its speed perception, while the effect depends on how much direction change of tangential velocity could be detected for a comparison stimulus.