• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.220-225
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• 2001

As numbers of serotonin's function are so many, studies of serotonin are numerous nowadays. In the beginning, concentration of metabolites such as 5-HIAA was a key issue, but recent studies have been challenged for serotonin receptor genes and their relation to mood disoder. Serotonin transporter(5-HTT) gene is a strong candidate gene of mood disoder for following reason. Serotonin transporter is a key protein in the serotonin pathway as it regulate the concentration of serotonin in the synaptic clept and essential pathophysiology of depression is dysregulation of 5-HTT so that all antidepressants have effect of 5-HTT antagonist. The decrease of 5-HTT in the platelet and in brain of the depressive patients is much consistent results in the studies of the pathophysiology of mood disorder till now. By this, we will be able to develop simple and easy marker for diagnosis, type, and treatment monitoring of depression. Many psychiatrists have sought the independent genes in relation to depression or schizophrenia. Obviously, the hereditary vulnerability contributes to etiology of mood disorders, but it is difficult to discriminate the independent genes because of many environmental factors. Moreover, in the hereditarily complex diseases such as mood disorder, the only vulnerability of gene can not sufficiently explain the etiology. In the future, to exclude the role of the gene-environmental interaction, the methods such as gene transfer can be considered. In the opposite direction, by using the gene destruction method, the role of target genes can be examined. As yet the concept of the gene expression, neural plasticity, neurogenesis and etc, is the elementary stage. The development of this field will help to establish the treatment strategy of chronic and refractory mood disorders.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.41-47
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• 2021

A wide range of studies have steadily pointed out the relation of oxidative stress to the primary and secondary causes of human disease and aging. As such, there have been multiple misconceptions about oxidative stress. Most of reactive oxygen species (ROS) generated from chronic diseases cause oxidative damage to cell membrane lipids and proteins. ROS production is increased by abnormal stimulation inside and outside in the body, and even though ROS are generated in cells in response to abnormal metabolic processes such as disease, it does not mean that they directly contribute to the pathogenesis of a disease. Therefore, the focus of treatment should not be on ROS production itself but on the prevention and treatment of diseases linked to ROS production, including types 1 and 2 diabetes, cancer, heart disease, schizophrenia, Parkinson's disease, and Alzheimer's disease. In this regard, Korean Red Ginseng (KRG) has been traditionally utilized to help prevent and treat diseases such as diabetes, cancer, inflammation, nervous system diseases, cardiovascular disease, and hyperlipidemia. Therefore, this review was intended to summarize in vivo animal and human clinical studies on the antioxidant activities of KRG and its components, ginsenosides.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.307-319
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• 2021

Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson's disease, Alzheimer's disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

• Korean Journal of Biological Psychiatry
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• v.21 no.1
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• pp.21-27
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• 2014

Objectives The aim of the present study was to investigate gender difference in empathic ability and recognition of facial emotion expression in schizophrenic patients. Methods Twenty-two schizophrenic outpatients (11 men and 11 women) and controls (10 men and 12 women) performed both the scale of Empathic Quotient (EQ) and facial emotion recognition test. We compared the scores of EQ and the facial emotion recognition test among each group according to diagnosis and gender. Results We found a significant sex difference in the scores of EQ and the facial emotion recognition test in the schizophrenic patients. And there were significantly negative correlation between the score of the facial emotion recognition test and the scores of Positive and Negative Symptom Scale (PANSS) in female schizophrenic patients. However, in male schizophrenic patients, there were no significant correlations between the score of each test and the scores of PANSS. Conclusions This study suggests that the sex difference in empathic ability and facial emotion recognition would be very important in chronic schizophrenic patients. Investigation of sex effects in empathic ability and facial emotion recognition in chronic schizophrenic patients would present an important solution for constructing optimal rehabilitation program.

• Korean Journal of Biological Psychiatry
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• v.11 no.2
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• pp.117-126
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• 2004

Objects:It has been reported that the incidence of tardive dyskinesia(TD), the remarkable abnormal involuntary movement, was higher in the schizophrenics with high blood sugar levels and that TD had been improved by small amount of insulin-injection for 90 days. And also it was generally known that the blood lipids were higher in the schizophrenics with tardive dyskinesia. Thus, we tried to replicate the correlations of abnormal involuntary movements with blood sugar levels and blood lipids in chronic schizophrenics treated with antipsychotics. Methods:Thirty-eight male schizophrenic inpatients who were stable in clinical state with medications, were included. The patients who had been already diagnosed as diabetes mellitus(DM), organic brain disorder, substance- related disorder, physical illness were excluded and also we excluded female patients to remove the hormonal effect on TD. Eleven patients who ranked higher(above five) in the Abnormal Involuntary Movement Scale(AIMS) were assigned into 2 groups, a dibenese group and a placebo group. Diabinese or placebos were administrated for 3 weeks with antipsychotics and AIMS was rechecked. Results:There were no correlations between the total AIMS scores and blood sugar and lipids levels in all subjects. The means of total and subscale scores(objective, face, and extremity) of AIMS did not reveal statistical significances between diabinese and placebo groups. However(total, jaw, face, upper arm, and objective feeling), were statistically higher in the diabinese group than those in the placebo group. And correlations of total cholesterol(TC) with fast blood sugar(FBS), weight with body mass index(BMI) and waist, total glycerol (TG) with BMI were statistically significant. Conclusion:In this study, there were statistical significances in the changes in ratings of AIMS scores between the diabinese group and the placebo group. Application of oral hypoglycemic agent might be a way of improving abnormal involuntary movements in schizophrenics with abnormal involuntary movements or TD. Althogugh it was not certain that there were correlations of abnormal involuntary movement with blood sugar and lipids, correlations of TC/TG with AIMS, of FBS with AIMS cautiously suggest that the regular check of $HbA_1C$, waist, and weight are recommended for schizophrenics.

• Korean Journal of Biological Psychiatry
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• v.10 no.2
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• pp.133-140
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• 2003

Objective:Some candidate gene polymorphisms were reported to be associated with tardive dyskinesia (TD). The aim of this study was to investigate the association of the 5-$HT_{2A}$ receptor gene polymorphisms with TD in Korean schizophrenic subjects. Method:Subjects were of 59 schizophrenic patients with TD and 60 schizophrenic patients without TD for studying of 5-$HT_{2A}$ receptor gene polymorphisms. TD was evaluated using the Abnormal Involuntary Movement Scale(AIMS). Genomic DNA was amplified by PCR and digestion with MspI and BsmI. Result:There were no statistically significant differences in the demographic variables, such as age, male to female percentage, duration of illnesses and duration of antipsychotic drug exposure between the TD group and control group. 1) T102C polymorphisms and TD Comparing the TD group and control group, the 102T/C allele was associated with a significantly increased risk for TD (${\chi}^2$=5.560, df=1, p=0.018). 2) Three AIMS categories of TD and T102C genotype. There were statistically significant differences in the three AIMS categories(${\chi}^2$=6.835, df=2, p=0.033). Conclusion:These result suggest 102T/C genotypes of the 5-$HT_{2A}$ receptor gene are related to the development of TD. The 102T/C genotypes were associated with significantly higher AIMS orofacial dyskinesia scores. These findings suggest that the 5-$HT_{2A}$ receptor gene is significantly associated with susceptibility to TD in patients with chronic schizophrenia.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.240-244
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• 1996

The effects of chronic treatment with haloperidol on the binding capacities of dopamine(DA) $D_2$-like receptor were investigated in rat striatum and olfactory tubercle. The authors tried to confirm the dose-response effects with usual dose and low dose haloperidol. Rats were treated with haloperidol(0.05, 0.15, 0.5, 1.5mg/kg/day in drinking water) for four weeks. Saturation analysis of the binding of [$^3H$]spiperone to striatal membranes showed that the haloperidol treatment(0.05, 0.5, 1.5mg/kg) induced significant proliferation. The changes of dissociation constant(Kd) were not significant in striatum. The maximal binding density(Bmax) and Kd increased remarkably following the treatment with usual dose haloperidol (1.5mg/kg) in olfactory tubercle. Although there was increasing trend other the treatment with low dose haloperidol, the change of Bmax was not significant statistically. The present findings indicate that low dose haloperidol induces the proliferation of DA $D_2$-like receptor in striatum and interact with the dopaminergic transmission which might underlie the antipsychotic effect. This finding may support the recent clinical suggestion on the low dose strategy in the treatment of schizophrenia.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.198-210
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• 1997

To examine the double-faced thymoleptic(antidepressant and antimanic) effects of risperidone in mood disorders, this article reviews the psychotropic-induced mania, thymoleptic effects of antipsychotics, therapeutic effects of risperidone and risperidone(RIS)-induced mania(RIM) in mood disorders, risk factors of RIM, possible neurochemical mechanism of these thymoleptic effects, pathophysiological and clinical significance of thymoleptic effects, and suggestive clinical guideline of RIS in mood disorders. RIS appeared effective for bipolar disorder at a lower dose than that recommended for schizophrenia, especially in the cases of maintenance of mood stabilizers, and gradual titration from low doses. Manic induction/exacerbation can occur by chance during RIS treatment in mood disorders, schizoaffective disorders, and schizophrenias. The possible risk factors for RIM are refractory mood disorder, especially in bipolar I disorder with poor initial response ; refractory schizoaffective disorders, especially in bipolar type with poor initial response ; refractory chronic schizophrenias, especially with initial responses ; psychotic features ; higher initial doses ; rapid titration ; combined therapy with antidepressants in refractory depression ; and RIS monotherapy in mania/hypomania. RIS is a drug that preferentially block 5-HT2 receptors. The effects of low dose are due mainly to the blockade of 5-HT2 receptors. There are more gradual increase in D2 blockade with increasing dose and this D2 blocking properties become apparent at higher doses. This may be related to a modulation of dopaminergic transmission by 5-HT2 antagonism at lower doses with the direct action of RIS on DA receptors coming into play at higher dose. The serotonergic antagonistic effect may be important for its effects on depressive symptoms. This, together with adequate blo-ckade of D2 receptors, may not necessarily lead to destabilization of mood disorder, but rather to more therapeutic effects. Therefore, this dose-receptor affinity relationship with both antidepressant and antimanic effects according to treatment duration can explain a continuum of antidepressant effect, antimanic effect, behavioral stimulation, and manic/hypomanic induction/exacerbation. It was the recognition of a useful psychiatric side effects by a thoughtful observer with fertile minds that led to their ultimate utilization as psychotropic drugs, i.e., phenothiazine, MAOI, TCA, and lithium. And, in vivo pharmacological challenge by novel psychotropics, as a neurochemical probe, with more specific actions is a useful tool to select pharmacologically homogeneous subgroup of the same phenotypical(clinical) condition, to further study the unknown underlying pathogenesis of various mental illnesses. Finally, RIS may be a useful alternative or adjunctive drug for patients with mood disorders without psychotic features or refractory to treatment with standard antipsychotic drugs. The more conservative doses(tirated slowly from 1-3 mg/d) of RIS, and maintenance of mood stabilizer in the cases with risk factors of RIM are recommended in mood disorder.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.16 no.2
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• pp.239-250
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• 2005

Objective : The purpose of this study was obtaining data on the efficacy and safety of risperidone in child and adolescent psychiatric patients. Method : Thirty one children and adolescents (males n=18, females n=13, age ranged from 5.4 to 17.3 years) treated with risperidone were selected among child and adolescent psychiatric inpatients of Seoul National University Hospital from January, 2001 to June, 2002, and charts for them were reviewed retrospectively. Results : The primary psychiatric disorders treated with risperidone were schizophrenia and other psychosis, bipolar I disorder with psychotic features, Tourette's disorder, autism spectrum disorders, mixed receptive and expressive language disorder, attention deficit-hyperactivity disorder, conduct disorder and obsessive-compulsive disorder. twelve of these had comorbid mental retardation. Primary target symptoms of risperidone were psychotic symptoms (n=13 or $41.9\%$), behavioral symptoms (n=10 or $32.3\%$) including aggression, impulsivity, hyperactivity, stereotypy nonresponsive to other psychiatric treatments, and chronic and severe tics (n=8, $25.8\%$). The efficacy of risperidone was measured by clinical global improvement (CGI) for target symptoms, $67.7\%$ of subjects showed moderate or marked improvements and its therapeutic effect appeared to be maintained during at least 7.5 months. Mean daily dosage of risperidone was $0.05{\pm}0.01mg/kg$, the group with psychotic symptoms had significantly higher mean daily dosage (0.07mg/kg) compared with other two groups (0.04mg/kg) with behavioral symptoms or tics. A variety of adverse events were reported in this study : weight gain (n=23) most commonly reported, extrapyramidal symptoms (n=15), autonomic symptoms (n=6), sedation (n=5) and symptoms related to hyperprolactinemia (n=2) etc. Although there was no drug change related to the adverse events of risperidone, and $90\%$ of subjects at their last visits were maintained on it, thus its tolerability appeared good. Conclusions Results suggest that risperidone may be relatively safe and effective drug in managing a wide variety of child and adolescent psychopathologies such as psychotic symptoms, behavioral symptoms including aggression, impulsivity, hyperactivity and stereotypy nonresponsive to other psychiatric treatments, and chronic and severe tics. Controlled and long-term studies of efficacy and safety of risperidone treatment for children and adolescents are recommended in the future.

• 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.