• 생물정신의학
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• 제8권2호
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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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• 제45권1호
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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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• 제25권4호
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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.

• 생물정신의학
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• 제21권1호
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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.

• 생물정신의학
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• 제11권2호
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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.

• 생물정신의학
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• 제10권2호
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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.

• 생물정신의학
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• 제3권2호
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• pp.240-244
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• 1996

흰쥐에 항정신병약물인 haloperidol을 장기간 투여한 뒤 줄무늬체와 후결절 조직에서의 DA $D_2$양 수용체의 변동에 대해 조사하였다. 약물투여군 4군에게 haloperidol을 각기 0.05, 0.15, 0.5, 1.5mg/kg/day이 되게끔 4주간 투여하였다. DA수용체의 변동은 [$^3H$]spiperone을 이용한 결합반응법을 통해 알아 보았다. 정상대조군에 비해 4주 동안 haloperidol을 투여받은 군 모두에서 줄무늬체에서의 DA 수용체의 최대 결합치가 증가한 것으로 나타났다. 기존의 연구에서 사용한 용량보다 대단히 낮은 0.05mg/kg/day을 투여받은 군 역시 유의한 증가를 보여 낮은 용량의 haloperidol이 DA계에 영향을 미치는 것을 알 수 있었다. 후결절조직의 최대결합치는 haloperidol투여군 모두에서 증가한 경향을 볼 수 있었으나 정상대조군에 비해 1.5mg/kg/day투여군에서 유의한 증가를 볼 수 있었다. 본 실혐의 결과로 미루어 낮은 용량의 haloperidol을 장기간 투여했을 때 뇌내 DA계에 수용체증식이 나타나며 항정신병 효과의 발현과도 관련성이 시사된다. 이러한 결과는 최근 거론되고 있는 항정신병약물의 저용량투여를 간접적으로 지지하는 것으로 생각되며 DA계의 연동을 알리는 다른 생물학적 지표와의 관련성을 살피면 흥미로운 결과를 얻을 것으로 기대된다.

• 생물정신의학
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• 제4권2호
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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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• 제16권2호
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• pp.239-250
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• 2005

목적 : 소아 청소년 정신과 환자에서 비전형 항정신병약물인 risperidone에 대한 효과 및 안전성에 대한 자료를 얻고자 하였다. 방법 : 2001년 1월에서 2002년 6월까지 서울대병원 소아 청소년 정신과 병동에 입원한 환자 중 risperidone이 사용되었던 5.4세에서 17.3세 사이의 환자 31명(남 18, 여 : 13)을 대상으로 후향적인 진료기록지 검토를 시행하였다. 결과 : Risperidone이 사용된 주된 정신과 진단은 정신분열병 및 기타 정신증, 정신병적 증상이 동반된 I형 양극성 장애, 뚜렛장애, 자폐스펙트럼 질환, 혼합형 표현성 및 수용성 언어장애, 주의력결핍 과잉행동장애 및 품행장애, 강박장애 등이었으며 이 중 12명에서 정신지체가 동반되었다. Risperidone사용의 주된 목표 증상은 정신병적 증상(n=13, $41.9\%$), 공격성, 충동성, 과잉행동, 상동증 등과 같은 행동 증상(n=10, $32.3\%$), 만성적이고 심한 틱 증상 (n=8, $25.8\%$)이었다. Risperidone의 효과는 risperidone의 목표 증상에 대한 CGI(Clinical Global Improvement)로 평가되었는데 $67.7\%$에서 중등도 이상의 호전을 보였고 평균 7.5개월 동안 치료효과가 유지되었다. Risperidone의 평균 하루 사용량은 $0.05{\pm}0.1mg/kg$이었으며, 정신병적증상군이 0.07mg/kg로 다른 두 증상군(0.04mg/kg)에 비해 의미 있게 높았다. 부작용으로는 체중증가(n=23)가 가장 흔하였으며 그 외 추체외로계 증상(n=15), 자율신경계증상(n=6), 진정작용(n=5), 고프로락틴혈증(n=2) 등 다양한 부작용이 보고되었다. 그러나 부작용으로 인해 약물을 변경한 경우는 없었으며 외래 마지막 방문 시 $90\%$에서 risperidone을 유지하고 있어 약물내약성은 비교적 우수한 것으로 평가되었다. 결론 : 비전형 항정신병 약물인 risperidone은 정신병적 증상, 공격성, 충동성, 과잉행동, 상동행동을 포함하는 행동증상, 만성적이고 심각한 틱증상 등 다양한 소아 청소년 정신병리의 치료에 비교적 안전하고 효과적인 약물이 될 수 있을 것으로 평가된다. 향후 risepridone의 효과 및 안전성에 대한 보다 장기적이고 체계적인 연구가 필요할 것이다.

• 생물정신의학
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• 제3권1호
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• pp.88-95
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• 1996

본 연구는 난치성 만성 정신분열병 남자환자 20명을 대상으로 항정신병약물인 haloperidol 올 2주간 일정량으로 유지한후 중추신경계에 비교적 선택적으로 작용하는 칼슘차단제인 nimodipine을 5주간 병합투여하였고 BPRS, Simpson-Angus Scale Averse events-Somatic Symptoms 등을 이용하여 nimodipine투여전, 투여후 1주, 3주, 5주에 임상반응을 평가하고 혈장 HVA, 5-HIAA농도를 투여전과 투여후 1주, 3주, 5주에 측정하여 다음과 같은 결과를 얻었다. 1) Nimodipine과 haloperidol의 병합투여시 전체 BPRS점수 및 사고소검사점수, 편집성소검사점수는 용량에 관계없이 기간에 따라 감소하는 추세를 보였으나, 특히 nimodipine 90mg을 병용투여하는 군의 경우 nimodipine투여전과 비교하여 3, 5주째에서 통계적으로 의미있게 감소하는 결과를 나타냈다(p<0.05). 2) Nimodipine과 haloperidol의 병합투여에 따른 부작용등은 통계적으로 의미는 없었으나 기간에 따라 감소하는 추세를 보였고, 임상적으로 관찰된 소견상 추체외로증상, 안구동통, 정서적 불안정, 심혈관계 부작용 등의 심각한 부작용은 없었다. 3) Nimodipine의 투여량 및 기간에 따른 혈장 HVA와 5-HIAA의 농도변화는 없었다. 4) BPRS점수가 20% 이상 감소하는 경우를 호전된 것으로 간주했을때 호전군과 비호전군간의 혈장 HVA 및 5-HIAA는 차이를 나타내지 않았고, 각 군에서 측정시기에 따른 차이도 보이지 않았다. 상기 결과로 보아 nimodipine이 혈장 HVA와 5-HIAA의 농도변화에 영향을 미치지 않으나 임상적인 호전은 나타내는 바 난치성 정신분열병환자, 노인환자나 항정신병 약물에 대해 부작용이 심한 정신분열병환자에서 nimodipine 병합사용이 유용할 것으로 사료된다.