비전형적 항정신병약물에 의한 체중증가의 기전 및 약리유전학

이준노,양병환,Lee, Joon-Noh,Yang, Byung-Hwan 대한생물정신의학회 2003 생물정신의학 Vol.10 No.1

The use of atypical antipsychotics is limited by occurrence of adverse reactions such as weight gain, despite of their benefits. This article provides a comprehensive review and discussion of the most significant findings regarding obesity-related pathways and integrates these with the known mechanism of atypical antipsychotic action. The focus of this article is primarily on the genetics of obesity related pathways that may be disrupted by atypical antipsychotics. This review also discussed weight gain, hyperglycemia or occurrence of diabetes while being treated with atypical antipsychotics from the point of view of pharmacogenetics. Pharmacogenetic research seeks to uncover genetic factors that will help clinicians identify the best treatment strategies for their patients. It will aid clinically in the prediction of response and side effects, such as antipsychotic-induced weight gain, and minimize the current "trial and error" approach to prescribing in the near future. This article also presents the genetics of both central and peripheral pathways putatively involved in antipsychotic-induced weight gain while providing a comprehensive review of the obesity literature. This article also review obesity related candidate molecules which may be disrupted during atypical antipsychotic drug treatment.

Ginsenoside Rg1 및 Rb1을 처리한 신경세포주(SH-SY5Y세포)의 유전자 발현양상

이준노,양병환,최승학,김석현,채영규,정경화,이준석,최강주,김영숙,Lee, Joon-Noh,Yang, Byung-Hwan,Choi, Seung-Hak,Kim, Seok-Hyun,Chai, Young-Gyu,Jung, Kyoung-Hwa,Lee, Jun-Seok,Choi, Kang-Ju,Kim, Young-Suk 대한생물정신의학회 2005 생물정신의학 Vol.12 No.1

Objectives:The ginsenoside Rg1 and Rb1, the major components of ginseng saponin, have neurotrophic and neuroprotective effects including promotion of neuronal survival and proliferation, facilitation of learning and memory, and protection from ischemic injury and apoptosis. In this study, to investigate the molecular basis of the effects of ginsenoside on neuron, we analyzed gene expression profiling of SH-SY5Y human neuroblastoma cells treated with ginsenoside Rg1 or Rb1. Methods:SH-SY5Y cells were cultured and treated in triplicate with ginsenoside Rg1 or Rb1($80{\mu}M$, $40{\mu}M$, $20{\mu}M$). The proliferation rates of SH-SY5Y cells were determined by MTT assay and microscopic examination. We used a high density cDNA microarray chip that contained 8K human genes to analyze the gene expression profiles in SH-SY5Y cells. We analyzed using the Significance Analysis of Microarray(SAM) method for identifying genes on a microarray with statistically significant changes in expression. Results:Treatment of SH-SY5Y cells with $80{\mu}M$ ginsenoside Rg1 or Rb1 for 36h showed maximal proliferation compared with other concentrations or control. The results of the microarray experiment yielded 96 genes were upregulated(${\geq}$3 fold) in Rg1 treated cells and 40 genes were up-regulated(${\geq}$2 fold) in Rb1 treated cells. Treatment with ginsenoside Rg1 for 36h induced the expression of some genes associated with protein biosynthesis, regulation of transcription or translation, cell proliferation and growth, neurogenesis and differentiation, regulation of cell cycle, energy transport and others. Genes associated with neurogenesis and neuronal differentiation such as SCG10 and MLP increased in ginsenoside Rg1 treated cells, but such changes did not occur in Rb1-group. Conclusion:Our data provide novel insights into the gene mechanisms involved in possible role for ginsenoside Rg1 or Rb1 in mediating neuronal proliferation or cell viability, which can elicit distinct patterns of gene expression in neuronal cell line. Ginsenoside Rg1 have more broad and strong effects than ginsenoside Rb1 in gene expression and related cellular physiology. In addition, we suggest that SCG10 gene, which is known to be expressed in neuronal differentiation during development and neuronal regeneration during adulthood, may have a role in enhancement of activity dependent synaptic plasticity or cytoskeletal regulation following treatment of ginsenoside Rg1. Further, ginsenoside Rg1 may have a possible role in regeneration of injured neuron, promotion of memory, and prevention from aging or neuronal degeneration.

만성 정신분열병 환자에서 Risperidone과 Clozapine이 체중과 혈당에 미치는 영향 - Haloperidol과의 비교 연구 -

남천우,양병환,이준노,Nam, Cheon-Woo,Yang, Byung-Hwan,Lee, Joon-Noh 대한생물정신의학회 2004 생물정신의학 Vol.11 No.2

Object:The goal of this study was to examine the changes in body weight and glucose levels of the patients treated with risperidone, clozapine or haloperidol in order to compare the effect of risperidone or clozapine with that of haloperidol. Methods:For nine months(January to September, 2003), a prospective study was performed in 60 patients with chronic schizophrenia who were in Seoul National Hospital. Two-week period was required for a drug wash-out. The patients were randomly assigned to risperidone, clozapine and haloperidol groups. They were given risperidone(n=20), clozapine(n=20) and haloperidol(n=20), respectively, everyday for 12 weeks. To examine the effects of these drugs on body weight and fasting glucose levels, we measured body weight and glucose levels of all the patients first without the drug treatment and at each end of 4, 8, and 12-week periods with the treatment. And we examined the differences among three groups in the changes of body weight and fasting glucose levels. Results:There were no significant differences in the changes of the body weight and fasting glucose levels between the atypical antipsychotics(risperidone or clozapine) and the typical antipsychotics(haloperidol). Conclusion:The study in the patients with chronic schizophrenia suggests that risperidone or clozapine do not cause any additional effects on body weight or glucose levels compared to haloperidol. 본 연구는 비전형적 항정신병약물이 체중과 혈당에 미치는 영향을 알아보고 그에 관계되는 여러 변인들의 관련성을 알아보고자 하였으며 이를 위해 비전형적 항정신병약물인 risperidone과 clozapine을 쓰는 환자 각각 20명, 대조군으로 전형적 항정신병약물인 haloperidol을 쓰는 환자 20명을 대상으로 입원 후 4주, 8주, 12주째 체중과 공복 시 혈당을 입원 초기 체중 및 혈당과 비교하였으며 각 약물군 간의 차이를 조사하여 다음과 같은 결과를 얻었다. 첫째, 연구 대상 환자의 초기 특성 상 clozapine군이 haloperidol과 risperidone군에 비하여 입원 시 체중이 높은 상태였는데 이는 clozapine을 복용하는 환자들이 이전에 haloperidol과 risperidone을 포함한 여러 가지 항정신병약물을 복용했던 경험이 있고 이로 인해 이미 어느 정도의 체중 증가가 있었던 것으로 생각해볼 수 있다. 둘째, 체중 변화는 risperidone과 clozapine군 모두 haloperidol을 쓴 군과 유의한 차이가 없었다. 셋째, 혈당 변화도 비전형적 항정신병약물인 risperidone과 clozapine군이 haloperidol군에 비해 의미 있는 차이가 없었다. 넷째, 몇 가지 변수들이 체중과 혈당의 변화에 연관성을 가지고 있었으나 그 정도는 크지 않았고 그 인과관계를 증명할 수는 없었다. 위의 결과들에서 볼 때 유병 기간이 길고 이전에 여러가지 항정신병약물을 복용한 경험이 있는 환자, 약물 복용에 따른 증상의 호전 정도가 두드러지지 않는 만성적인 정신분열병 환자들에서는 비전형적 항정신병약물이 전형적 항정신병약물에 비해 체중 변화와 혈당의 수치를 변화시키는 경향이 크지 않다는 점을 알 수 있었다.

벤라팍신이 PC12 세포의 신경돌기 성장에 미치는 영향

오홍석,최준호,이준석,이준노,최미란,채영규,김석현,양병환,Oh, Hong-Seok,Choi, Joon-Ho,Lee, Jun-Seok,Lee, Joon-Noh,Choi, Mi-Ran,Chai, Young-Gyu,Kim, Seok-Hyeon,Yang, Byung-Hwan 대한생물정신의학회 2003 생물정신의학 Vol.10 No.2

Objectives:The purpose of this study is to examine the effects of venlafaxine, one of novel antidepressant drugs, on neurite growth in PC12 cells. Methods:PC12 cells were cultured with NGF for eight days. Then different concentrations($0{\mu}M$, $1{\mu}M$, $5{\mu}M$) of venlafaxine were mixed with cultured PC12 cells. After 24 hours and 48 hours of culture, we compared the effects of venlafaxine on the total length of neurites of cultured PC12 cells between no venlafaxine treated group($0{\mu}M$) and venlafaxine treated groups($1{\mu}M$ and $5{\mu}M$). Additionally, we studied the concentration-dependent effect of venlafaxine on differentiation in PC12 cells. Results:Experimental results showed that 1) the mean length of neurites in $1{\mu}M$ and $5{\mu}M$ venlafaxine treated group was more increased than no venlafaxine treated group(p=0.002). 2) the length of neurite in $5{\mu}M$ venlafaxine treated group was more elongated than $1{\mu}M$ venlafaxine treated group(p=0.046). 3) the length of neurite in $6{\mu}M$ venlafaxine treated group was more elongated than all the other concentrations in our experiment. Above $6{\mu}M$, the length of neurite was shortened in inverse proportion to the concentration of venlafaxine. Conclusions:This results suggest that venlafaxine, one of novel antidepressant drugs, promotes the differentiation of neuron. This study is believed to be a first step toward understanding the molecular and cellular mechanisms of antidepressant treatment.

증상 안정기의 노년기 우울증에서 심혈관 위험과 인지기능 장애 간의 관련성 : 예비연구

황인선(Insun Hwang),임선진(Seon-Jin Yim),이준노(Joon-Noh Lee),송윤영(Yun Young Song),홍경기(Kyungki Hong),홍문화(Moon-Hwa Hong),윤해주(Hai Joo Yoon),엄주란(Jooran Eom) 대한노인정신의학회 2015 노인정신의학 Vol.19 No.2

Objective:The purpose of this study was to test the hypothesis that cardiovascular risk is associated with cognitive impairments in clinically stable late-life depression. Methods:A total of 59 clinically stable late-life depression patients over age 60 were enrolled in a cross-sectional study. Evalu-ation tools used in this study include Hamilton Rating Scale for Depression, Geriatric Depression Scale, State-Trait Anxiety Inven-tory, the Framingham general cardiovascular disease risk profile and the cognitive function battery designed for this study. Corre-lation analysis, analysis of variance and analysis of covariance were performed. Results:Patients with higher cardiovascular risk performed significantly poorer in the domains of executive function and short-term or long-term memory. In models adjusted for age, sex, education, 10% higher cardiovascular risk was associated with poorer executive function. Conclusion:Our findings suggested that cardiovascular risk could be a significant factor associated with poor executive func-tion in clinically stable late-life depression and the management which is necessary as a component of treatment planning. This pi-lot study provided good prospects for future studies to document this relationship on larger samples.

주관적 인지장애를 호소하는 지역사회 노인에 대한 다요인 인지능력 향상프로그램(‘씽씽두뇌 발전소’)의 효과성 검증을 위한 비교 연구

김효진 ( Hyojin Kim ),임선진 ( Seon-jin Yim ),이준노 ( Joon-noh Lee ),이원혜 ( Won Hye Lee ),한주현 ( Joo Hyun Han ),김경미 ( Kyungmi Kim ),김가영 ( Kayoung Kim ) 한국정신병리진단분류학회 2020 精神病理學 Vol.24 No.2

Objectives: This study explored the effects of nonpharmacological multifactorial memory improvement program (‘Ssing-Ssing Doonoi baljeonso (SSD)’) developed by the National Center of Mental Health in 2015 in community-dwelling elderly complaining of subjective memory impairment (SMI). Methods: A randomized, controlled, 8-weeks trial of SSD with double-blind assessments at baseline and end-point of treatment. A total of 117 elderlies with SMI were recruited from 10 community-based welfare centers in Seoul, Korea. Participants were randomly assigned to two groups: SSD and art therapy group. 8 sessions of treatment were administrated to the groups. Results: SSD significantly improved immediate recall, delayed recall of word memory test, all items of the logical memory test, and immediate recall, delayed recall, and recognition of the visuospatial function test (all p<0.05). Korean short version of Geriatric Depression Scale(S-GDS-K) was also significantly improved, and Memory Efficacy Questionnaire(MEQ), Prospective-Retrospective Memory Questionnaire(PRMQ), and Korean Dementia Screening Questionnaire(K-DSQ) were all significantly improved. In particular, compared to the art therapy group, the K-DSQ showed better results(time * group, F(1, 114)=6.585, p=0.012, η²=0.055), and S-GDS-K was a tendency to improve in SSD group (time * group, F(1, 114)=3.596, p=0.060, η²=0.031). Conclusion: Our multifactorial memory training program significantly enhanced memory, visuospatial function, mood and subjective memory efficacy. Compared with art therapy, SSD had more advantages in memory function of daily life and showed a tendency to improve depression. It is likely to be applied as a nonpharmacological treatment for the prevention of cognitive decline in the elderly with SMI/MCI.

에탄올 처리에 의한 흰쥐 신경아교종(Glioma) 세포에서의 유전자 발현 - DNA 칩을 이용한 분석 -

이소희,오동열,한진희,최인근,전양환,이준노,이태경,정종현,정경화,채영규,Lee, So Hee,Oh, Dong-Yul,Han, Jin-Hee,Choi, Ihn-Geun,Jeon, Yang-Whan,Lee, Joon-Noh,Lee, Tae Kyung,Jeong, Jong-Hyun,Jung, Kyung Hwa,Chai, Young-Gyu 대한생물정신의학회 2007 생물정신의학 Vol.14 No.2

연구목적: 알코올의존에 내재된 분자생물학적 기전을 이해하고 알코올리즘 치료 약물의 새로운 표적을 알아내기 위해서는, 알코올에 반응하는 유전자 혹은 반응 경로를 알아내는 것이 필요하다. DNA microarray 기법의 발달로 고전적 연구 방법과 달리 동시에 수천 수만개의 유전자의 표현을 검사하는 것이 가능하게 되었다. 본 연구에서는 알코올을 흰쥐의 신경아교종 세포에 처리했을 때 어떤 유전자의 발현을 조절하는지 DNA microarray를 이용하여 알아보고자 하였다. 방 법: 흰쥐 신경아교종 C6 세포주를 배양하여 에탄올 처리하고 총 RNA를 분리한 후 유전자 발현 양상을 조사하기 위해 cDNA microarray를 수행하였다. 결 과: 에탄올 처리군과 대조군간의 유전자 발현의 차이를 비교 분석한 결과 에탄올이 처리된 군에서 대조군에 비해 15개의 유전자가 발현이 증가하였고 12개의 유전자가 발현이 감소하였다. 발현이 증가한 유전자는 Orthodenticle(Drosophila) homolog 1, procollagen type II, adenosine A2a receptor, GATA-bindning protein2를 포함하고 있었고, 발현이 감소한 유전자는 diacylglycerol kinase beta, PRKC, Protein phosphatase 1, clathrin-associated protein 17, nucleoporin p58, proteasome를 포함하였다. 결 론: 흰쥐의 신경아교종 세포주에 알코올을 처치하였을 때 급성기에 알코올에 반응하여 발현이 증가하거나 감소한 유전자는 전반적으로 전사의 조절, 신호전달체계, 허혈성 뇌손상의 중재, 신경세포의 퇴행에 관여하는 것들이었다. 본 연구는 유전자 발현 시스템을 이용하여 에탄올에 반응하는 새로운 후보 유전자들을 관찰하였다는데 의의가 있다. Objetives : Identification of target genes for ethanol in neurons is important for understanding its molecular and cellular mechanism of action and the neuropathological changes seen in alcoholics. The purpose of this study is to identify of altered gene expression after acute treatmet of ethanol in rat gliom cells. Methods : We used high density cDNA microarray chip to measure the expression patterns of multiple genes in cultured rat glioma cells. DNA microarrays allow for the simultaneous measurement of the expression of several hundreds of genes. Results : After comparing hybridized signals between control and ethanol treated groups, we found that treatment with ethanol increased the expression of 15 genes and decreased the expression of 12 genes. Upregulated genes included Orthodenticle(Drosophila) homolog 1, procollagen type II, adenosine A2a receptor, GATA bindning protein 2. Downregulated genes included diacylglycerol kinase beta, PRKC, Protein phosphatase 1, clathrin-associated protein 17, nucleoporin p58, proteasome. Conclusion : The gene changes noted were those related to the regulation of transcription, signal transduction, second messenger systems. modulation of ischemic brain injury, and neurodengeneration. Although some of the genes were previously known to be ethanol responsive, we have for the most part identified novel genes involved in the brain response to ethanol.

식도운동질환과 위식도역류의 연관성

김지향 ( Ji Hyang Kim ),이풍렬 ( Poong Lyul Rhee ),홍성노 ( Sung Noh Hong ),이준행 ( Joon Haeng Lee ),김영호 ( Young Ho Kim ),손희정 ( Hee Jung Son ),김재준 ( Jae Jun Kim ),백승운 ( Seung Woon Paik ),이종철 ( Jong Chul Rhee ) 대한소화기기능성질환·운동학회 2005 Journal of Neurogastroenterology and Motility (JNM Vol.11 No.1

목적: 식도운동질환과 위식도역류질환과의 연관성을 시사하는 여러 연구가 보고되고 있다. 이 중 새로이 분류된 비효과적 식도운동은 위식도역류질환의 주요 식도내압검사 소견으로 일부 연구에서는 위식도역류질환의 표지라고 주장되기도 하지만 논란이 되고 있으며, 이를 제외한 다른 식도운동질환에서 위식도역류질환의 빈도와 연관성을 살펴본 연구는 부족한 상황이다. 이에 저자 등은 새로운 진단 기준을 적용하여 식도운동질환과 위식도역류질환과의 연관성을 분석하였다. 대상 및 Background/Aims: There have been controversies on whether IEM is the marker for pathologic acid exposure, and the relationship between the other motility disorders and pathologic acid exposure has been studied only rarely. This study was done to evaluate

정신분열병 환자에서 carbamazepine이 혈청 haloperidol 농도에 미치는 영향

이준노,양병환,김미경,신현아,고현철 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

The author examined the sequential changes of serum haloperidol(HP) levels after administration and subsequent withdrawal of carbamazepine(CBZ) in chronic schizophrenic patients for further understanding of the enzyme induction of cytochrome P450(CYP) in relation to these two drugs. The serum HP levels were measured by high performance liquid chromatography(HPLC) with UV detector. Twenty-five patients who were maintained with haloperidol for a month or more completed in this study of CBZ induced sequential changes of the serum HP levels. Subjects were performed with multiple samples at baseline, each 1 week and 4 weeks after CBZ administration and 1 week and 4 weeds after subsequent withdrawal of CBZ. CBZ caused a significant decrease of the serum HP levels at 1 week(t=7.747 p=0.000) and 4 weeks(t=5.899 p=0.000) compared with the baseline levels, but no significant changes of the HP levels at 4 weeks compared with 1 week(t=-0.639 t=0.529). After subsequent withdrawal of CBZ, the serum HP levels are increased at 1 week(t=-3.392 p=0.002) and 4 weeks(t=-3.839 p=0.001) more than those of the HP and CBZ combination therapy for 4 weeks. The changes of HP levels were not significant at 4 weeks compared with 1 week after the withdrawal of CBZ(t=-1.509 p=0.144). There is no difference of the HP levels between baseline and 4 weeks after the withdrawal of CBZ. These results suggest that CBZ decreased serum HP levels by induction of the CYP isozymes which metabolize HP, and CYP induction complete almost within the first week and thereafter it seems to be disappeared. After abrupt discontinuation of CBZ, the HP levels were elevated quite rapidly within a week by deinduction of CYP isozymes, and then the HP level was increased nonsignificantly, ultimately reached the baseline level. The reason that the duration of deinduction was long period more than those of induction seems to be due to the remained CBZ in the body that did not excreted.

장기간 혈액투석을 받는 말기 신부전환자의 정서상태 및 투석 순응도에 대한 연구

이준노,김창현,권택술 大韓神經精神醫學會 1995 신경정신의학 Vol.34 No.4

The purpose of this study is to evaluate the relationship between compliance of patients under hemodialysis and their affective states of depressed mood and anxiety. Subjects consist of 58 end-stage renal failure patients on the long-term hemodialysis of one year or longer. Depressed state was evaluated with Beck Depression Inventery(BDI) and anxiety state was assessed with Self-rating Antiety Scale(SAS). The compliance in terms of diet, medication and fluid was assessed with Potassium(K), Phosphorus(P) and Interdialytic Weight Gain(IWG), respectively. the primary findings are as noted below. 1) 58.6% of the subjects felt depressed, but anxiety level was quite within normal range. 2) There were no intercorrelations between the compliance parameters of diet, education and fluid intake. preliminary correlations are as follows. The level of depression correlated with that of anxiety. Educational level is correlated negatively with scores of depression and anxiety. Duration of marriage is correlated positively with scores of depression. 3) Only anxiety, not depression, correlated with IWG, when controlled for age, sex and other clinical variables. But, anxiety did not correlate with K and P. This result may suggest that IWG is a more sensitive indicator of compliance than K and P.