Relationship between First-Episode Schizophrenic Psychopathology and 99m-Tc-ECD SPECT Regional Cerebral Blood Flow and Plasma Homovanillic Acid / 대한정신약물학회지

OBJECTIVE: The purpose of this study was to examine the relative blood flow differences of brain regions between first-episode schizophrenic patients and normal controls and the relationships between these regions and the changes of psychopathology scores, the treatment response, after serotonin dopamine antagonist (SDA) risperidone treatment. Another purpose of this study was to investigate SPECT relative blood flow index as the treatment response predictor of SDA treatment under control of the influences of homovanillic acid (HVA). We hypothesize that there is differences in the brain blood flows examined by SPECT between first-episode schizophrenic patients and normal controls. Relative blood flow index examined by SPECT will be the response predictors of SDA treatment of schizophrenia under control of influences of metabolites. METHODS: The relative blood flows of seventeen first-episode schizophrenic patients and ten normal controls were examined by 99m-Tc ECD SPECT before drug treatment. The patients group was treated for 6 weeks with SDA. The psychopathology was assessed at baseline just before SDA trial and then at 2 weeks and 6 weeks after SDA treatment. At the same time plasma HVA was evaluated by HPLC (high performance liquid chromatography). RESULTS: The cerebral blood flow of first-episode schizophrenic patients was decreased in thalamus and left basal ganglia and the relative blood flow index of schizophrenic patient's left thalamus was significant therapeutic predictor of SDA treatment of positive symptoms under control of the HVA influnences. CONCLUSION: These results suggest that the relative blood flow examined by SPECT will be a therapeutic index of SDA treatment in schizophrenia.

Relationship between Risperidone-Induced Therapeutic Response and Plasma Homovanillic Acid and 5-Hydroxyindoleacetic Acid Levels in Patients with Schizophrenia / 대한정신약물학회지

OBJECTIVES: This study was purposed to examine the changes of plasma homovanillic acid(HVA), 5-hydroxyindoleacetic acid(5-HIAA), and HVA/5-HIAA ratio during an 8-week risperidone trial and to investigate the relationship between the plasma monoamine metabolites and risperidone-induced treatment resposes. METHOD: Eighteen schizophrenic patients were treated for 8 weeks with risperidone. The psychopathology was assessed at baseline just before risperidone trial and then at 1st week, 2nd week, 4th week, and 8th week using the Positive and Negative Syndrome Scale(PANSS) and the Clinical Global Impression scale(CGI). The plasma HVA and 5-HIAA levels were measured using high performance liquid chromatography with electrochemical detection method. RESULTS: 39% of the patients treated with risperidone was categorized as responders, who showed at least a 20% decrease in PANSS total score at the end point of the study. At the end point of the 1st week, there was significant difference in the percent change of plasma HVA between responders(39% increment) and nonresponders(9% increment). But no significant differences in the percent change of plasma 5-HIAA and the percent change of plasma HVA/5-HIAA ratio between responders and nonresponders were observed. CONCLUSION: These results suggest that the magnitude of the early increase of plasma HVA may be associated with risperidone-induced treatment response in schizophrenia.

Comparison of the Treatment Effect Between Higher and Lower Plasma Homovanillic Acid Groups in Schizophrenic Patients / 대한정신약물학회지

This study explored the differences of clinical response, plasma homovanllic acid concentration, haloperidol and reduced haloperidol concentration after 4 weeks haloperidol treatment between higher and lower baseline homovanllic acid concentration groups of schizophrenic patients. After a 2-weeks washout period, they entered the 4 week haloperidol treatment period. The psychopathology was assessed at baseline just before haloperidol trial and then at 1, 2, 4 week using Positive and Negative Syndrome Scale(PANSS). Also the measurement of plasma homovanillic acid(HVA), haloperidol(HP) and reduced haloperidol(RHP) levels were assessed with high performance liquid chromatography at the same time of PANSS assessments. There were no significant differences on the positive, negative, general symptom score of PANSS, haloperidol and reduced haloperidol levels at the end of 4-week between higher plasma HVA group(bsaeline pHVA> or =12.69ng/ml, 10 subjects) and lower plasma HVA group(bsaeline pHVA<12.69ng/ml, 9 subjects). In higher group, the treatment response mainly occured in 2 weeks after treatment, but in lower group, that occured therough 4 weeks. And in higher group, pHVA decresed constantly, but in lower group, pHVA did not changed in 4 weeks. There was significant correlation between plasma haloperidol levels and the clinical improvement(persentile improvement of PANSS positive, general symptom, total score) at the end of 4 week. But no significant correlation were found between plasma reduced haloperidol and RHP/HP ratio and clinical improvement. These results suggest that baseline HVA level is not a valuable therapeutic predictor but it is able to suggest that higher baseline pHVA group and lower group may have different pathophysiology.

Relationship between Therapeutic Response and Plasma HVA/5-HIAA Ratio in Newly Admitted Schizophrenia / 대한정신약물학회지

Twenty newly admitted acute schizophrenic patients were treated with haloperidol for 6 weeks. HVA and 5-HIAA were sampled at baseline, 3days after initial neuroleptic dose, and after 1, 2, 3, 4, 6 weeks of treatment. Nine patients were classified as responders in this prospective haloperidol treatment trial. They had a score of change in the BPRS total scores of 25% or greater. Eleven patients were classified as nonresponders, based on a score of changes in the BPRS total scores of less than 25%. 1) There was no significant difference in plasma HVA/5-HIAA ratio between responder and non-responder before and after haloperidol treatment. 2) There was no significant correlations between plasma HVA/5-HIAA ratio and BPRS total scores. This study could not support the hypothesis that neuroleptic treatment would be effective by changing dopamine and serotonin function and/or by altering their interaction.

Relationship between Clozapine-Induced Therapeutic Responses and Plasma Homovanillic Acid and 5-Hydroxyindoleacetic Acid Levels in Patients with Chronic Schizophrenia

This study was done to examine changes of plasma homovanillic, acid(HVA), 5-hydroxyindoleacetic acid(5-HIAA), and HVA/5-HIAA ratio during an 8-week clozapine trial and to investigate the relationship between the plasma monoamine metabolites and treatment responses. Twenty-seven chronic schizophrenic patients were treated for 8 weeks with clozapine. The psychopathology was assessed at baseline just clozapine trial and then every 2 weeks until the end of 8-week clozapine treatment using the positive and Negative Syndrome Scale(PANSS) and the Clinical Global Impression scale(CGI). The plasma HVA and 5-HIAA levels were measured also biweekly using high preformance liquid chromatography with electrochemical detection method. Plasma HVA and 5-HIAA levels were significantly decreased during a 8-week chozapine treatment, although plasma HVA/5-HIAA ratio showed no significant change. The changes of plasma HVA levels were in significant correlations with the changes of PANSS positive scores, of general psychophathology scores, and changes of total scores. The changes of plasma 5-HIAA levels were in significant correlations with the changes of PANSS negative scores. But the changes of plasma HVA/5-HIAA ratio had no significant correlation with any PANSS subscale score changes. 48% of the patients treated with clozapine was categorized as responders, who showed at least a 20% decrease in PANSS total score and a CGI severity score of mildly ill or less(< or =3) of the end pint of the study. The baseline plasma HVA levels and HVA/5-HiAA) ratio were significantly higher in responders(N=13) than in nonresponders(N=14). But no significant difference in the change of plasma HVA between responders(40.3% decrement) and nonresponders(3.1% increment). But no significant difference in the change of plasma 5-HIAA and the change of plasma HVA/5-HIAA ratio between responders and nonresponders were observed. These results suggest that the antipsychotic effect of clozapine on positive symptoms may be associated with dopaminergic blocking activity, and that on negative symptoms may be associated with serotonergic blocking activity. The baseline plasma HVA levels and the change of HVA levels from baseline may be useful predictors of treatment response with clozapine.

A Comparative Study of Clinical Effects and Changes of Plasma HVA and 5-HIAA on Risperidone vs Haloperidol in Chronic Schizophrenic Patients / 대한정신약물학회지

OBJECTIVES: This study was designed to compare risperidone(as an atypical antipsychotic) with haloperidol(as a typical antipsychotic), so we examined the clinical effects and changes of plasma HVA, 5-HIAA & HVA/5-HIAA ratio after 8 week of risperidone or haloperidol trial. METHOD: Twenty-six male chronic schizophrenic patients were treated for 8 weeks with risperidone(N=14) and haloperidol(N=12). The duration of wash-out period was 14 days. The psychopathologic assessment was chechked by Positive and Negative Syndrome Scale(PANSS) and plasma HVA & 5-HIAA was measured by High Performance Liquid Chromatography(HPLC) with electrochemical detector. The checking points were just before drug trial and 1st, 2nd, 4th, and 8th week(total 5 times). RESULTS: 1) Risperidone trial group were more improved than haloperidol tiral group in PANSS scores(total, positive, negative and general psychopathy). 2) Changes of plasma HVA and 5-HIAA in the risperidone and haloperidol trial group were not statistically different. But because baseline 5-HIAA of risperidone trial group was higher than that of haloperidol trial group, the increase of haloperidol trial group would be more. 3) There was significant difference in changes of HVA/5-HIAA ratio between risperidone and haloperidol trial group. But the change of HVA compared with 5-HIAA in risperidone trial group was higher than that of haloperidol trial group. CONCLUSION: These results revealed that risperidone was more effective in clinical symptoms, and suggest that cause of these results may be due to blocking both of dopamine D2 receptors and serotonin 5-HT2 receptors of risperidone.