• 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.2 no.1
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• pp.91-99
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• 1995

A on-off study was designed to evaluate the effects of addition of transdermal esrtradiol to tricyclic antidepressants on depression level, vasomotor symptom(hot flush), sexual functions and hormonal status, plasma 5-hydroxyindoleascetic acid(5-HIAA) level in postmenopausal women with depression. Plasma level of estradiol, progesterone, LH, FSH, prolactin and 5-HIAA was measured by Time-resolved fluoroimmunoassay and HPLC(High Performance Liquid Chromatography). To asses their symptoms, the BDI(Beck Depression Inventory) and modified symptom scale, extracted from women's health questionnaire were used. Depression score, sexual function score were decreased by the last 4-weeks of addition of transdermal estradiol to antidepressant treatment, not Significant, but vasomotor symptom (hot flushes) score was decreased significantly(p<0.05) by the last 4-weeks of the given treatment. Thus, during addition of transdermal estradiol to antidepressants treatment, only vasomotor symptom(hot flushes) was improved significantly, but depression level was not changed in postmenopausal women with depression. Plasma FSH, estradiol and prolactin level was not changed in postmenopausal women with depression. Plasma FSH, estradiol and prolactin levels were increased by the last 4-weeks of the treatment. There were not significant correlations between clinical symptoms and plasma hormonal status and 5-HIAA level in baseline. After the last 4-weeks of transdermal estradiol treatment, the change of depression score was correlated significantly with change of serum prolactin and 5-HIAA level and the change of vasomotor symptom score was correlated significantly with the change of plasma prolactin level.

• 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.3 no.2
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• pp.269-276
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• 1996

Object : The aim of this study was to examine an association between plasma 5-Hydroxyindoleacetic Acid(HIAA) level and the change of depressive symptom after fluoxetine trial in haloperidol-stabilized schizoprenic in-patients. Method : According to plasma 5-HIM level, 32 patients were classified to either group with high 5-HIAA level(N=11) or that with low 5-HIM(N=11). For each patient, fluoxetine(20mg/day) added to stable haloperidol dose for 6 weeks. The authors measured Hamilton Rating Scale for Depression (HRSD) at baseline, the 2nd week, the 4th week, the 6th week of treatment. Result : 1) Age, duration of illness, number of admission, duration of present admission, dosage of haloperidol between high 5-HIAA group and low 5-HIM group were significantly different. 2) As time went on, the association between the change of depressive symptom and plasma 5-HIAA concentration was not significant. 3) Of depressed group, as lime went an, depressive symptoms were improved significantly in high 5-HIAA group, but not in law 5-HIM group. Conclusion : We suggest that the association between plasma 5-HIAA level and the change of depressive symptoms after fluoxetine trial in haloperidol stabilized schizophrenic in-patients was not significant.

• 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.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.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.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.811-816
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• 1999

Background : Nausea and vomiting associated with chemotherapy are common side effects which remain difficult to control. Acute phase nausea and vomiting (0-24 hours after induction of chemotherapy) parallels plasma serotonin release, which explains the effectiveness of $5-HT_3$ receptor antagonists. Serotonin released from gastrointestinal enterochromaffin cells may mediate chemotherapy-induced emesis. In this study, we analyzed urinary excretion of 5-HIAA, the main metabolite of serotonin. Methods : Eight men and four women were studied in their cisplatin chemotherapy cycle. Urinary 5-hydroxyindoleaoetic aicd (HIAA) levels were determined before and during a 24-hour period under ondansetron prophylaxis. Results : Urinary 5-HIAA excretion for a 24-hour period was increased in all patients after induction of cisplatin (P=0.002). Conclusion : Cisplatin chemotherapy is associated with serotonin release in the acute phase. Our finding may provide evidence for a relationship between emesis and serotonin following cisplatin chemotherapy.

• Journal of Nutrition and Health
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• v.27 no.2
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• pp.153-161
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• 1994

We fed high trypotophan diet(3.5% tryptophan/diet(w/w) to mice for 7 days and treated then with 3 hour immobilization(IMMB) stress to investigate tryptophan metabolism and immunomodulation. The levels of serum tryptophan, brain tryptophan, serotonin(5HT) and 5-hydroxyindoleacetic acid(5HIAA) in the tryptophan diet fed animals were higher than those of the normal diet fed animals. Feeding tryptophan supplemented diet to stressed animal significantly decreased the levels of serum and brain tryptophan and 5HT levels. However, the amount of 5HIAA which is the metabolite of serotonin was increased in brain. Plasma corticosterone level was increased by the stress in both groups but the degree of this increase was smaller in high tryptophan fed animals. The relative numbers of CD8+ T cells, CD4+ T cells and B cells in spleen were decreased in high tryptophan diet fed and stressed animals compared to control diet fed and no stressed animals. CD8+ T cells decreased more than CD4+ T cells. The decrease of CD8+ T cells in high tryptophan fed and stressed animals was similar to that in high tryptophan fed animals or normal diet fed and stressed animals. Stress and tryptophan supplement acted synergistically to decrease the number of B cells. This study suggests that stress and tryptophan supplement could modify the number of lymphocyte cells, and indicates that the interaction of stress and tryptophan supplement on immune fuction depends on the types of immune cells.

• Journal of Nutrition and Health
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• v.29 no.5
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• pp.472-479
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• 1996

To investigate the effect of dietary lipids and stress on brain catecholamine and serotonin concentration, sixty three weanling male Sprague-Dawley rats(mean body weight$\pm$SD : 171$\pm$3g) were fed a diet containing fish oil, soybean oil or beef tallow and than, each was exposed to three different types of stress, isolated, grouped or cold, respectively. Cold stress seemed to be most severe and living together in a large cage with some playing equipments is more stressful than living alone in a classical small cage evidenced by plasma corticosterone level. Average food intake and body weight gain were not significantly different among exprimental groups. In adrenal catecholamines, norepinephrine was significantly affected by diet and stress and dopamine was by stress. Norepinephrine concentration of the fish oil group was lowest among diet groups. Adrenal epinephrine, however, was not. It was also shown than the cold stress significantly increased the brain norepinephrine concentration. The cold stress significantly induced higher content of brain serotonin than the grouped stress. However, the concentratin of 5-hydroxyindoleacetic acid(5-HIAA), the metabolite of serotonin, was not significantly different among groups. Therefore, this results suggest that stress affects sympathetic neuronal activity, and fish oil might lighten the burden of stress.