• Korean Journal of Biological Psychiatry
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• v.4 no.1
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• pp.95-101
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• 1997

The recent hypothesis about the pathophysiology of schizophrenia has been centered mainly on two theories, i.e. dopamine hypothesis and serotonin hypothesis. We investigate the correlations between plasma monoamine metabolite concentrations and clinical symptoms in schizophrenic patients. The first purpose of our study was to examine whether the plasma levels of HVA(homovanillic acid) and 5-HIAA(hydroxyindoleacetic acid) are significantly different in schizophrenics, compared to normal controls. And, with the intention of clarifying the interaction between dopaminergic system and serotoninergic system, the ratio of HVA/5-HIAA also was measured. The second purpose was whether the basal(pre-treatment) levels of these metabolites show the correlation with clinical symptoms. Finally, third purpose was whether basal HVA and 5-HIAA levels can be held as a predictor of treatment response. We used Scale for the Assessment of Positive Symptoms(SAPS) and Scale for the Assessment of Negative Symptoms(SANS) as the clinical symptom rating scales. Our results were as followed, 1) only the level of basal plasma HVA was significantly differ in schizophrenics. 5-HIAA and HVA/5-HIAA were not. 2) basal HVA showed significant correlation with SAPS score, especially delusion subscale. 3) the higher was the basal HVA level, the more improvement in clinical symptoms was observed. The basal 5-HIAA level and the HVA/5-HIAA ratio did not show any significant findings. These results support the dopamine hypothesis of schizophrenia, but fail to examine on the possible involvement of serotonin in schizophrenia.

• Korean Journal of Biological Psychiatry
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• v.5 no.2
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• pp.243-247
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• 1998

The authors tried to confirm the significant changes of plasma homovanillic acid(HVA) concentration after insulin administration in comparison with those of usual diurnal variation in the same subjects. Male patients with schizophrenia taking neuroleptics were participated in a study of diurnal variation and insulin induced dopaminergic perturbation, with multiple samplings at baseline, 30minutes, 60minutes and 90minutes after insulin administration(n=18). Ten patients were sampled at baseline and 60minutes after insulin administration. There was a diurnal variation of plasma HVA concentrations, which decreased gradually from 8 am to 9:30 am. We confirmed that regular insulin(0.1 unit/kg) blocked the normal diurnal variations and increased plasma HVA concentrations. This pattern was not correlated with clinical variables, such as age, onset age, duration of illness and presence of family history. Schizophrenic patients were grouped by the positive and negative syndrome scale. In contrast to our previous study, the concentrations of positive and negative groups were similar at baseline. The HVA concentrations of negative group after insulin administration were higher than those of positive group without statistical significance. We have a plan to modify the current insulin-HVA method. In the near future, we will try to confirm whether the modified insulin-HVA method can be used as a biological indicator for the elucidation of complex clinical manifestations of schizophrenia.

• Korean Journal of Biological Psychiatry
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• v.4 no.1
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• pp.84-94
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• 1997

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 patiens 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 clozapine 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 socres. The changes of plasma 5-HIAA levels were in signfificant 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 socre and a CGI severity score of mildly ill or less(${\leq}3$) at 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 baseline levels of plasma 5-HIAA was found between responders and nonresponders. At the end point of the study, there was significant difference in the change of plasma HVA between responders(40.3% decrement) and nonresponders(3.1% increment). But no signficant differences 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.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.116-122
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• 2001

Objectives : Schizophrenia manifests a variety of interindividual differences in therapeutic response to antipsychotics. This might be attributable to dopamine and serotonin receptors that a important target for various antipsychotics, and the $D_3$ receptor(DRD3) alleles they carry. The purpose of our study was to investigate whether the plasma levels of homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(HIAA), and the polymorphism of DRD3 can be held as a predictor of treatment response in chronic schizophrenic patients. Methods : Therapeutic response for 116 korean schizophrenia patient treated during 48 weeks were assessed by PANSS used as the clinical symptom rating scales. The levels of concentration of HVA and 5-HIAA were examined by HPLC at baseline and at 48 weeks. We classified the polymorphism of DRD3 receptor using amplifying by polymerase chain reaction(PCR). Results : Neither concentrations of HVA and 5-HIAA nor genotype of dopamine 3 receptor were not significantly associated with the therapeutic response. But, the patients who has A1 alleles of DRD3 gene showed poor therapeutic responses. Conclusion : A1 allele of DRD3 gene is associated with poor prognosis of chronic schizophrenia.

• Korean Journal of Biological Psychiatry
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• v.2 no.1
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• pp.77-90
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• 1995

The Purposes of this study were to examine plasma homovanillic acid(pHVA) levels and 5-hydroxyindoleacetic acid(pHIAA) levels in schizophrenics during haloperidol treatment, and to assess the association of pHVA and pHIM levels with their psychopathology and treatment responses. Fourteen patients entered the study and pHVA, pHIAA levels were measured at baseline, first week, second week and fourth week during treatment. Also, plasma haloperidol levels were measured at first week, second week and fourth week. Psychopathology was evaluated with Brief Psychiatric Rating Scale(BPRS) at baseline, 1st week, 2nd week and 4th week. 1) There were significant differences on the duration of illness and total BPRS scores at baseline between higher pHVA group(baseline pHVA level >7.72ng/mL) and lower pHVA group(baseline pHVA level <7.72ng/mL). 2) There was no significant difference on the duration of illness between higher pHIM group(baseline pHIAA level >3.18ng/mL). and lower pHIAA group(baseline pHIAA level <3.18ng/mL). 3) The Means of pHVA levels at 1 st week and 2nd week after treatment decreased significantly in the higher pHVA group and did not change in the lower pHVA group. 4) In the higher pHIAA group, the mean of pHIAA levels at 4th week after treatment decreased significantly, but did not change in the lower pHIAA group. 5) Between the higher pHIVA group and lower pHVA group, the response rates(percentile improvement) after treatment were not different from each other, but there was significant difference on the response rate between the lower pHIAA group and higher pHIM group at 2nd week. 6) There was significant correlation between total BPRS scores and pHVA levels in the higher pHVA group during treatment. The results suggest that repeated measurement of pHVA levels and pHIAA levels following antipsychotic treatment have prognostic significance for response. Also, shcizophrenics whose have relatively nigh levels of pHVA, or relatively low levels of pHIAA before treatment will show a favorable early responses to antipsychotics.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.262-268
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• 1996

It has been known that clozapine is more selective mesolimbic dopamin $D_2$ receptor antagonist and related to 5-HT receptor. In this study, we wxamined the plasma homovanillic acid(HVA), serotonin(5-HT), and 5-hydroxyindoleacetic acid(5-HIM) levels in refractory schizophrenics during clozapine treatment. And we assessed the effects of clozapine on these plasma monoamine metabolites and their association with psychopathology and treatment response. Eight refractory schizophrenic patients(DSM-IV) have entered the study for 3 months during clozapine treatment. Patients were admitted to the inpatient sevice and withdrawn from all neuroleptics for 7-14 days but exceptionally occasional doses of lorazepam was given if needed for behavioral control. The dose of clozapine was titrated as tolerated to 800mg/day. The plasma HVA. 5-HIM and 5-HT levels were measured before treatment and following 2nd week, 4th week, 8th week, and 12th during treatment. Psychopathology was assessed with Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Synrome Scale(PANSS) before and during clozapine treatment. During clozapine treatment, no statistically significant changes were found in plasma HVA, 5-HIM, 5-HT levels, and HVA/5-HIM ratio between baseline and following 2nd week, 4th week, 8th week, 12th week. However, the change in plasma 5-HIAA/5-HT ratio from baseline to 4th week was statistically significant. Generally, changes of plasma HVA, 5-HIAA, 5-HT levels and HVA/5-HIAA ratio were not associated with psychopathology but 5-HIAA was associated with in positive symptoms and general psychopathology of PANSS. These results suggest that clozapine has been found to have relatively weak dopaminergic blokade and stronger serotonergic antagonism.

• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.88-95
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• 1996

In an open labeled study, two fixed doses of nimodipine(45mg and 90mg daily) were added to the usual antipsychotic drug treatment (Haloperidol : mean dose=25mg/day) in 20 male chronic schizophrenics for 5 weeks. The purposes of this study were to evaluate the therapeutic effects and the effect an the changes of plasma homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(5-HIAA) levels. The results were as follows : 1) Total BPRS score and thought cluster, paranoid cluster subscores showed linear decreasing trend over the course of the study(P<0.05). Especially the thought cluster and paranoid cluster subscores were significant difference between 45mg and 90mg dose of nimodipine(P<0.05). The improvement rates were 45,45% of 90mg and 11.11% of 45mg, but there was no significant difference between the 45mg and 90mg dose of nimodipine. 2) The scores of extrapyramidal symptoms and adverse events-somatic symptoms showed a linear decreasing trends over the course of study. 3) The changes in the mean plasma HVA and 5-H1AA concentrations by the dosages and durations of combining of nimodipine were not statistically significant. 4) There was no statistical significance in plasma HVA and 5-HIAA of the improved, non-improved goroup. Nimodipine has a possibility os on adjunctive agent for treatment resistant schizophrenics, elderly patients and liable patients for the Side effects to usual antipsychotic drugs. So we suggest that the dosage of nimodipine must be above 90mg/day in the treatment of schizophrenia.