• 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.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.

• Journal of Microbiology and Biotechnology
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• v.33 no.12
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• pp.1657-1670
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• 2023

This study aimed to evaluate the effects of Limosilactobacillus fermentum and Lactiplantibacillus plantarum isolated from human feces coordinating with inulin on the composition of gut microbiota and metabolic profiles in db/db mice. These supplements were administered to db/db mice for 12 weeks. The results showed that the Lactobacillaceae coordinating with inulin group (LI) exhibited lower fasting blood glucose levels than the model control group (MC). Additionally, LI was found to enhance colon tissue and increase the levels of short-chain fatty acids. 16S rRNA sequencing revealed that the abundance of Corynebacterium and Proteus, which were significantly increased in the MC group compared with NC group, were significantly decreased by the treatment of LI that also restored the key genera of the Lachnospiraceae_NK4A136_group, Lachnoclostridium, Ruminococcus_gnavus_group, Desulfovibrio, and Lachnospiraceae_UCG-006. Untargeted metabolomics analysis showed that lotaustralin, 5-hydroxyindoleacetic acid, and 13(S)-HpODE were increased while L-phenylalanine and L-tryptophan were decreased in the MC group compared with the NC group. However, the intervention of LI reversed the levels of these metabolites in the intestine. Correlation analysis revealed that Lachnoclostridium and Ruminococcus_gnavus_group were negatively correlated with 5-hydroxyindoleacetic acid and 13(S)-HpODE, but positively correlated with L-tryptophan. 13(S)-HpODE was involved in the "linoleic acid metabolism". L-tryptophan and 5-hydroxyindoleacetic acid were involved in "tryptophan metabolism" and "serotonergic synapse". These findings suggest that LI may alleviate type 2 diabetes symptoms by modulating the abundance of Ruminococcus_gnavus_group and Lachnoclostridium to regulate the pathways of "linoleic acid metabolism", "serotonergic synapse", and" tryptophan metabolism". Our results provide new insights into prevention and treatment of type 2 diabetes.

• 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.

• YAKHAK HOEJI
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• v.35 no.4
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• pp.326-331
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• 1991

Brain serotonin and its utilization was investigated on stressed rats after feeding high tryptophan diet for a month. High tryptophan fed rats displayed significantly higher level of serum tryptophan, brain tryptophan, serotonin (5-hydroxytryptamine; 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) than the control diet fed rats. When rats were treated with 3 hour immobilization (IMMB) stress, serotonin turnover was slightly increased, but not statistically significant, in control diet group rats. However in high tryptophan diet rats, 3 hr IMMB stress resulted in statistically significantly (p<0.05) decreased the serum tryptophan, brain tryptophan and 5-HT level. The concentration of 5-HIAA was significantly increased indicating accelerated utilization of the brain 5-HT of the high trp. fed rat. The utilization pattern of the serotonin was found to be similar among young and adult rats. Rats on a tryptophan enriched diet displayed higher coping ability to the stress as they exhibited smaller increment of corticosterone level. A possble involvement of opioid system was suggested in serotonin utilization by measuring total $^{3}$[H]-naloxone binding in brain.

• 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.

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.101-119
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• 2004

Ginseng Radix Alba and Cyperi Rhizoma were investigated for their anti-depressant effects. For this purpose, forced-swimming test, tail suspension test, hot plate test, reserpine-induced hypothermia, aggressive behavior test were performed. In addition, the brain content of 5-hydroxyindoleacetic acid(a metabolite of serotonin), the monoamine oxidase activity, anticonvulsant effect, sleep enhancement effect were determined. The results are as follows: In the forced swimming test, Ginseng Radix diminished the duration of immobility by 45.5% compared to the control group, while Cyperi Rhizoma showed weaker effect (12.4% reduction) at 2g/kg. In the tail suspension test, the effect of Ginseng Radix(43.7% reduction) are also better than that of Cyperi Rhizoma(15.6% reduction) at 2g/kg. In the hot plate test, Ginseng Radix showed no difference as compared to control, while Cyperi Rhizoma increased the jump latency time by about 25% after administration for 10 days. In the reserpine-induced hypothermia test, both drugs slowly dropped the body temperature compared to the control group, especially the rate of hypothermia of Ginseng Radix was 24.0% at 1g/kg. In the aggressive behavior test, both drugs delayed the onset time, decreased the duration and frequency, of which effects were better in Cyperi Rhizoma. The content of 5-hydroxyindoleacetic acid in mice brain was slightly increased in Ginseng Radix, while Cyperi Rhizoma increased its level almost to the control group. Both drugs inhibited the monoamine oxidase activity in a dose-dependent manner, but the effect(51.2%) of Cyperi Rhizoma was more potent than the effect(11.8%) of Ginseng Radix. In the pentobarbital-induced sleep test, Cyperi Rhizoma exhibited no significant difference against the control group, while Ginseng Radix showed about two-fold enhancement at 2g/kg. The anticonvulsant effect of both drugs delayed the onset time, shortened the duration of convulsion and diminished the lethality, but Ginseng Radix were better than Cyperi Rhizoma.

• 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.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.1-9
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• 1992

Catecholamines, serotonin and their metabolites were measured in the posterior hypothalamus of urethane-anesthetized normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) using brain microdialysis which is a recently developed experimental method to measure the release of neurotransmitters and their metabolites at the localized brain area in vivo. Microdialysis probe was implanted stereotaxically to the rat posterior hypothalamus and perfused by Ringer's solution. Monoamines and their metabolites were quantified by reverse phase high performance liquid chromatography with electrochemical detection. In vitro recovery test of microdialysis showed that there exist inverse relationship between the perfusion flow rate and the relative recovery of neurochemical compounds. The estimated extracellular concentration of dopamine was about 32 nM, of norepinephrine 50 nM, of epinephrine 50 nM, of serotonin 73 nM, of 3, 4-dihydroxyphenylacetic acid (DOPAC) 281 nM, of homovanillic acid (HVA) 181 nM, and of 5-hydroxyindoleacetic acid (5HIAA) 3767 nM in the hypothalamic perfusate of the normotensive rat. There was no difference in the basal level of monoamines between the SHR and the WKY. In contrast, the level of DOPAC, HVA and 5HIAA in SHR was higher than that in the WKY, This study demonstrated that the microdialysis technique should be an applicable tool for in vivo measurement of central neurochemical substances.