• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.7 no.1
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• pp.77-91
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• 1996

In order to elucidate the biological etiology and the effects of comorbidity on biological variables in tic disorders, plasma serotonin (5-hydroxlfryptamine, 5-HT) and 5-hydroxy- indoleacetic acid (5-HIAA) we.e measured in 87 tic disorders and 30 control subjects. The 87 tic disorder were composed of 45 Tourette's disorder(TS), 22 chronic motor tic disorders (CMT) and 20 transient tic disorders (TTD). Among these patients,43 patients were pure tic disorder (PT), 28 subject also had attention deficit hyperactivity disorder (T+ADHD) and 16 subjects had obsessive compulsive disorders (T+ OCD) as comorbid disorders. The results are summarized as follows : 1) Plasma 5-HT levels showed significant positive correlations with plasma 5-HIAA levels (Pennon r=0.77, p<0.05). 2) Plasma 5-HT and 5-HIAA levels showed no significant correlation with age in tic disorders. 3) Plasma 5-HIAA and 5-HT levels showed no significant correlations with age in control subjects. 4) There was significant difference in plasma 5-HT levels among TS, CMT, TTD and control groups (ANOVA F=34.48, df=3, 113, p<0.01), and post-hoc test using Scheffe method showed significant differences between control and TS, control and CMT, control and ITD groups. But, post-hoc test showed no significant differences between TS and CMT, TS and TTD, CMT and TTD groups. 5) There was significant difference in plasma 5-HIAA levels among TS, CMT, TTD and control groups (ANOVA F=26.48, df=3, 113, p<0.01), and post-hoc test using Scheffe method showed significant differences between control and TS, control and CMT, control and TTD groups. But, post-hoc test showed no significant differences between TS and CMT, TS and TTD, CMT and TID groups.f) There was significant difference in plasma 5-HT and 5-HIAA levels among PT, T+ADHD, T+OCD and contol groups (ANOVA 5-HT, F=37.59, df=3, 113, p<0.01, 5-HIAA, F=27.37, df=3, 113, p<0.01), and post-hoc test using Scheffe method showed signiscant differences between control and PT, control and T+ADHD and control and T+OCB. But, post-hoc test showed no significant differences between PT and T+ADHD, PT and T+ OCD and T+ADHD and T+ OCD. These results show that decreased 5-HT and 5-HIAA levels may play a role in the genesis of tic disorders, but these findings have no significant correlations with the severity of tic disorders. And the comorbid disorders of tics may have minimal effects on the biochemical abnormalities. Future studies must be focused on the effects of serotonin agonists and antagonists on tic disorders and molecular biological methodology may enhance to elucidate the mechanisms of these abnormal findings.

• 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.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.14 no.1
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• pp.112-122
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• 2003

Objectives：Considerable data indicate that diminished serotonergic activity is related to aggressive behavior. In order to understand the biological etiology in conduct disorder, we studied the relationships of plasma serotonin and 5-HIAA levels in conduct disorders to measures of aggression, violation of rules and oppositional defiant behavior. Methods：Subjects were selected from inpatients and outpatients department of the Division of Child and Adolescent Psychiatry of Seoul National University Hospital. 41 conduct disorders(18 childhoodonset type, 23 adolescent-onset type) and 23 normal controls were included in this study. For the assessment of aggression, rule violation and oppositional behavior, parents completed the rating scale for conduct disorder and oppositional behavior based on the DSM-IV diagnostic criteria. Plasma serotonin and 5-HIAA levels were determined by HPLC with electrochemical detection. Results：1) Plasma 5-HT and 5-HIAA levels were not significantly different among childhood-onset conduct disorder, adolescent-onset conduct disorder and normal control subjects. 2) No significant correlations were found between plasma 5-HT levels and aggression or rule violation. 3) Plasma 5-HT levels showed significant positive correlations with oppositional behavior both in childhood-onset conduct disorder and adolescent-onset conduct disorder. 4) Age-related changes were not found in plasma 5-HT and 5-HIAA levles. Conclusion：Our findings do not support the hypothesis that dysregulation of serotonergic function may be associated with aggresson. Instead, our data suggest that serotonergic function is more closely related with oppositional behavior than aggression.

• 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.

• Journal of Ginseng Research
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• v.16 no.3
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• pp.183-189
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• 1992

Effect of the standardized ginseng extract(G115) on the central monoaminergic systems were investigated in comparison with that of halcperidol in rats. Immediately after sacrificed by decapitation, the strlata and frontal cortex were removerl. Concentations of the monoamines dopamine and serctorLin and their metabolites were deterinintd by HPLC-EC. G115 increased the concentration of 5-HIAA and DOPAC/UA ratio in striatum. However, dopaminrrgic neuronal activities were not affected by G115 that decreased the concentratio,Is of 5-HT and 5-HIAA in frontal cortex. G115 in combination with apomorphine significantly irlcreased the concentration of DA and S-HT but decreased the DO PAC/DA ratio and 5-HIAA/5-HT ratio only in frontal cortex. These results suggest that G115 like HPD inhibits the activity of nigrostriatal dopamine neuron in striatum. However, unlike HPD it activates central monoaminergic neuron activity in frontal cortex.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.1-6
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• 1990

We established an in vitro system of central serotonergic neurons by culturing dissociated rat embryonic (El4) brainstem cells to 14 days in vitro and monitored the serotonergic neuronal growth by measuring 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents in the cells with hish performance liquid chromatography with electrochemical detection (HPLC-EC). We studied also tile effects of various drugs on the contents of 5-HT and 5-HIAA, confirming in vivo reports. The 5-HT content (13 ng/mg protein) and 5-HT turnover rate (17 pmol/mg protein/h) at 14 days in vitro were in good agreement with those reported in the adult rat brain. The 5-HT content was more easily depleted with p-chlorophenylalanine, a tryptophan hydroxylase inhibitor than with NSD 1015 (3-hydroxybenzylhydrazine), an aromatic L-amino acid decarboxylase (AADC) inhibitor. Incubation of the cultures with tryptophan or 5-hydroxytryptophan increased the rate of serotonin formation implying that neither tryptophan hydroxylase nor AADC is saturated with its amino acid substrate in this in vitro system . The 5-HT content was depleted by reserpine. The 5-HT and 5-HIAA contents were increased and decreased, respectively, by monoamine oxidase inhibitors. All the above results indicate that the biochemical properties of the central serotonergic neurons in this culture system reflect reliably those of central serotonergic neurons in vivo. We suggest that measuring 5-HT and 5-HIAA contents in the primary cultured dissociated brainstem-cells with HPLC-EC is useful in the study of pharmacology as well as toxicolgy of the central serotonergic neurons.

• Biomolecules & Therapeutics
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• v.9 no.1
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• pp.20-25
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• 2001

In this study we fed control diet and tryptophan supplemented diets containing 0.35% tryptophan to ICR mice for 2 weeks. The concentrations of serotonin and 5-HIAA were changed by injection of the serotonin synthesis inhibitor, p-CPA and the serotonin precursor, serotoninP and the change of brain serotonin concentration negatively correlated with that of pain sensitivity, and p-CPA and serotoninP also changed the analgesic effect of morphine. The injection of naloxone, the opiate antagonist, resulted in an increase in the writhing frequency, but its antagonistic effect was not significant. The concentration of 5-HIAA elevated in mice brain at least 3hr after administration of morphine hydroxide indicates that the changes in brain serotonin metabolism may be associated with the acute effects of morphine analgesia. In short, these results not only suggest that tryptophan supplemented diet suppress pain sensitivity in mice, but also indicate that at least in part analgesic mechanism of serotonin may be associated with morphine analgesia.

• 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.

• Toxicological Research
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• v.14 no.4
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• pp.495-500
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• 1998

The effect of acute toluene exposure on behaviour and monoamine concentrations in the various brain regions were investigated in the rat. Toluene was adminstered via inhalation to rats at concentrations of 0, 1000, 10000, 40000 ppm for 20 min. During exposure to toluene, spontaneous locomotor activity was counted. After exposure, animals were sacrificed instantly and brains were separated. Regional concentratons of brain monoamines (norepinephrine, NE; dopamine, DA; 5- hydroxytryptamine, 5-HT) and its metabolites (3,4-dihydroxyphenylacetic acid, DOPAC; homovanillic acid, HVA; 5-hydroxyindole-3-acetic acid, 5-HIAA) were determined. The changes in locomotor activity during toluene exposure depended on the toluene concentration. At 1000 ppm concentration, spontaneous locomotor activity increased initially and thereafter decreased. At higher concentrations (10000 ppm and 40000 ppm), spontaneous locomotor activity decreased and eventually ceased. A regional analysis of VA, NE, 5-HT, VOPAC, HVA, and 5-HIAA indicated a significant decrease in VA concentrations in cerebellum and striatum while NE and 5-HT concentrations were significantly increased in the cerebellum and cortex. 5-HIAA concentrations were significantly increased in all brain regions. DOPAC concentrations were significantly increased in cerebellum and cortex while decreased in striatum. These results especially indicated that metabolic conversion of DA to HVA in striatum was highly increased by toluene inhalation. However, It remains to elucidate between behavioural responses and monoamine changes.