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Pharmacogenomics and Schizophrenia (약물유전체학과 정신분열병)

  • Lee, Kyu Young;Chung, In Won
    • Korean Journal of Biological Psychiatry
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    • v.8 no.2
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    • pp.208-219
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    • 2001
  • The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

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Association Study between Serotonin 1A Receptor Gene rs6295 Polymorphism and Tardive Dyskinesia in Patients with Schizophrenia (조현병 환자에서의 지연성 운동이상 발생과 세로토닌 1A 수용체유전자 rs6295 다형성과의 연관성)

  • Lee, Youn-Jung;Namgoong, Yoon;Cho, Areum;Lee, Heon-Jeong
    • Korean Journal of Schizophrenia Research
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    • v.23 no.2
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    • pp.71-77
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    • 2020
  • Objectives: Tardive dyskinesia (TD) is a movement disorder that is characterized by hyperkinetic movements. Previous studies have suggested that the serotonergic systems are correlated with TD vulnerability. In this study, the association between a single-nucleotide polymorphism (SNP) of the serotonin 1A receptor gene (HTR1A) rs6295 and TD was investigated. Methods: We investigated whether HTR1A rs6295 SNP is associated with antipsychotic-induced TD in 280 Korean patients with schizophrenia. Patients with schizophrenia having TD (n=105) and those without TD (n=175) were matched for their antipsychotic exposures and other relevant variables. The HTR1A rs6295 SNP was analyzed using polymerase chain reaction (PCR)-based methods. Results: There was no significant difference in the distribution of genotypic (χ2=2.70, p=0.26) and allelic (χ2=1.87, p=0.17) frequencies between the patient groups with TD and without TD. There was no significant difference in total abnormal involuntary movement scale score (F=0.39, p=0.68) among the genotype group either. Conclusion: Although there were no differences in genotypic and allelic frequency between patient groups with and without TD, further studies on association of TD with other SNPs of HTRA1 are needed to understand the pathophysiological mechanism of TD.

The effects of Korean Red Ginseng on stress-related neurotransmitters and gene expression: A randomized, double-blind, placebo-controlled trial

  • Jihyun Yoon;Byoungjin Park;Kyung-Won Hong;Dong-Hyuk Jung
    • Journal of Ginseng Research
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    • v.47 no.6
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    • pp.766-772
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    • 2023
  • Background: Korean Red Ginseng (KRG) is an effective anti-stress treatment. In this study, we investigated the therapeutic potential effects of KRG on relieving stress in a general population using transcriptome analysis. Methods: We conducted an 8-week clinical pilot study on 90 healthy men who reported stress. The study was completed by 43 participants in the KRG group and 44 participants in the placebo group. Participants were randomized 1:1 to the KRG and placebo groups. We evaluated the stress by stress response inventory (SRI) at baseline and 8 weeks. The main outcomes were changes in the levels of neurotransmitters (NTs) and NT-related gene expression. NTs were analyzed using automated (GC) content, and levels of gene expression were measured by reads per kilobase of transcript per million mapped reads (RPKM). Results: The KRG group showed significantly preserved epinephrine decrease compared with placebo group at 8 weeks (changes in epinephrine, KRG vs. placebo; -1623.2 ± 46101.5 vs. -35116.3 ± 86288.2, p = 0012). Among subjects who higher SRI score, meaning stress increased compared to baseline, the KRG group showed a smaller decrease in serotonin than the placebo group (changes in serotonin, KRG vs. placebo; -2627.5 ± 5859.1 vs, -8087.4 ± 7162.4, p = 0.005) and a smaller increase in cortisol than the placebo group (changes in cortisol, KRG vs. placebo; 1912.7 ± 10097.75 vs. 8046.2 ± 8050.6 , p = 0.019) in subgroup analysis. Transcriptome findings indicated that KRG intake affects gene expression related with metabolism of choline, adrenalin, and monoamine. Conclusion: These findings suggest that KRG has beneficial effects on the amelioration of stress response in NTs, and this effect is more prominent in stressful situations. Further clinical studies are required to confirm the anti-stress effect of KRG.

Chemical Compositions and DPPH Radical Scavenger Activity in Different Sections of Safflower (홍화의 부위별 화학성분과 DPPH Radical 소거 활성)

  • Kim, Jun-Han;Kim, Jong-Kuk;Kang, Woo-Won;Ha, Young-Sun;Choi, Sang-Won;Moon, Kwang-Deog
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.5
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    • pp.733-738
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    • 2003
  • Chemical compositions and DPPH radical scavenger activity in different sections of safflower (Carthamus tinctorious L.) were investigated. Protein contained 28.39% in sprout and fat contained 20.47% in seed, respectively. Linoleic acid as predominant unsaturated fatty acid of safflower contained 80.01% in sprout and 78.27% in seed. Glucose contained 1253.6mg% in sprout and fructose contained 970.7mg% in sprout. Sucrose contained 912.0mg% in flower bud. Succinic acid was included 2795.3 mg% in flower, malic acid was included 2054.8mg% in leaf. K as minerals contained 2826.8mg% in leaf and 2613,6 mg% in sprout, Ca contained 1999.8mg% in leaf and 1160.9mg% in sprout. Total phenolics contained 5.8%, 4.7%, 4.4% in flower, sprout and leaf, and total flavonoid contained 6.5%, 2.5%, 2.0% in flower, sprout and leaf, respectively Serotonin-I (Ν- [2- (5-hydroxy - l Η- indol -3- yl)ethyl] ferulamide) as serotonin compounds was determined 147.7mg% in seed, serotonin - II (Ν-[2-(5-hydroxy-lΗ-indo-1-3yl )ethyl]-p-coumaramide) was determined 155.4 mg% in seed. Acacetin as flavonoid compounds was contained 116.5mg% in seed. Luteolin as flavonoid compounds was identified 388.3mg% in sprout, luteolin 7-glucoside was determined 692.3mg% in leaf, respectively. DPPH radical scavenger activity was measured by DPPH method, it was shown higher 114.2% in ethanol extract of flower and 113.6% in ethanol extract of leaf than 88.05% of 100 ppm BHA as chemical antioxidant.

Preparation of Functional Healthy Drinks by Ethanol Extracts from Defatted Safflower Seed Cake (탈지 홍화씨박 에탄올추출물 함유 기능성 건강음료의 제조)

  • 김준한;김종국;강우원;김귀영;최명숙;문광덕
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.7
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    • pp.1039-1045
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    • 2003
  • Functional healthy drinks were processed with freeze dried powders of ethanol extract from of defatted safflower (Carthamus tinctorious L.) seed cake and some useful components of the drinks were investigated. Yield of freeze dried powder was the highest as 8.42% when it extracted with 60% ethanol (60% EFDP). Each drink contained 0.02% of freeze dried powder and ranged 10.6∼13.8% of soluble solid, 2.90∼3.68 of pH, 0.10∼0.83% of titratable acidity. ‘L’ value of drink-I (DSD-I) was the highest as 94.82$\pm$2.45, ‘b’ and ‘a’ value of drink-V (DSD-V) was highest as 27.15-2.65 and 28.67$\pm$2.69, respectively. Major free sugars of drink were 6015.3∼7918.2 mg% of glucose and 1511.4∼2091.0 mg% of sucrose. The content of citric acid was the highest as 179.2∼981.3 mg%. The content of total phenol in 60% EFDP was 99.17 mg% and that of drink-II(DSD-II) and DSD-V was 307.84 mg% and 224.06 mg%, respectively. Total flavonoid was contained as 50.29 mg% in 80% ethanol extract (80% EFDP) and 125.20 mg% in DSD-V. N-[2-(5-hydroxy-1H-indol-3-yl) ethyl] ferulamide (serotonin-I) was determined as high as 18.81 ppm in 80% EFDP and ranged 2.42∼2.89 ppm in drinks. N-[2-(5-hydroxy-lH-indol-3yl)ethyl]-p-coumaramide (serotonin-II) was determined as 30.17 ppm in 80% EFDP and ranged 3.79∼4.59 ppm in drinks. Acacetin, flavonoid compound were 9.83 ppm in amyloglucosidase hydrosis + 60% ethanol extract (A + 60% EFDP) and ranged 0.98∼1.26 ppm in drinks. Electron donating ability (EDA, %) was measured and compared with 100 ppm BHA as chemical antioxidant. EDA was 93.97$\pm$2.21% in A+60% EFDP, 94.79$\pm$2.26% in DSD-I, 94.69$\pm$1.37% in DSD-II, and 93.83$\pm$1.49% in BHA. DSD-II added with hot water extract solution from Korean ginseng and safflower yellow pigment recorded the highest sensory score.

The Relationship between Taq I A Dopamine $D_2$ Receptor Polymorphism and Therapeutic Response to Antipsychotics in Schizophrenic Patients (정신분열병환자에서 Taq I A 도파민 $D_2$ 수용체 다형성과 항정신병약물의 치료반응과의 연관)

  • Kang, Cheol Joong
    • Korean Journal of Biological Psychiatry
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    • v.12 no.2
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    • pp.107-113
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    • 2005
  • Purpose:In an attempt to predict the interpersonal differences of therapeutic response to antipsychotic drugs on pharmaco-genetic bases, this study was designed to investigate the relationship between the therapeutic response to antipsychotic drugs and Taq I A dopamine $D_2$ receptor polymorphism in schizophrenic patients. Methods:The subjects were 158 patients diagnosed with schizophrenia(DSM-IV). The therapeutic response to antipsychotic drugs was evaluated using the Treatment Response Scale(TRS) retrospectively. Patients were divided into two groups, dopamine receptor antagonist responders, and serotonin-dopamine antagonist responders. The patients' Taq I A dopamine $D_2$ receptor polymorphism was determined by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP). Results:The dopamine receptor antagonist responders had the A1 allele in significantly higher incidences (${\chi}^2$(1)=4.875, p=0.027, two-tailed). No significant difference was found among the serotonin-dopamine antagonist responders between those with or without the A1 allele. Conclusions:The patients with the A1 allele responded better to dopamine receptor antagonists than those with no A1 allele. Based on these results, it is suggested that the pharmacological effect of dopamine receptor antagonists can be predicted depending on the presence of the A1 allele in schizophrenic patients.

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Immunohistochemical studies on the distribution of neuropeptides in the tongue of Korean native goat (한국재래산양 혀에 분포하는 신경전달물질에 관한 면역조직화학적 연구)

  • Lee, Heungshik S.;Lee, In-se;Kang, Tae-cheon
    • Korean Journal of Veterinary Research
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    • v.36 no.2
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    • pp.265-276
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    • 1996
  • This study was performed to identify the localization of several neuropeptides; calcitonin gene-related peptide(CGRP), substance P(SP), vasoactive intestinal polypeptide(VIP), neuropeptide Y(NPY), serotonin(5-HT) and neurotensin in the tongue of Korean native goat(Capra hircus) by immunohistochemical method. The results were summarized as follows: CGRP- and SP-immunoreactive fibers were observed as moderate immunoreactivity at the subepithelial plexus and subgemmal fibers in lamina propria of lingual papillae, but not seen in intragemmal, intergemmal, perigemmal fibers as well as in the supporting, basal and taste cells. Fibers around the acinus of the von Ebner's gland and blood vessels showed weak immunoreactivities against CGRP and SP. In the intrinsic ganglion cells, CGRP- and SP-immunoreactivities were not observed. The distribution patterns of VIP- and NPY-immunoreactive fibers were similar to CGRP-or SP-immunoreactive fibers, but their immunoreactivities were stronger than those of CGRP- or SP immunoreactive fibers. The immunoreactivities to VIP or NPY were seen in the intrinsic ganglion. Only a few serotonin immunoreactive fibers were seen in some filiform or fungiform papillae. Neurotensin immunoreactivity was not observed in the tongue of Korean native goat.

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Recent Development on Future Antidepressants (미래의 항우울제:어떠한 것들이 개발되고 있는가?)

  • Kim, Yong-Ku
    • Korean Journal of Biological Psychiatry
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    • v.11 no.1
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    • pp.14-25
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    • 2004
  • The current understanding of the mechanisms of pharmacotherapy for depression is characterized by an emphasis on increasing synaptic availability of serotonin, noradrenaline, and possibly dopamine, while minimizing side effects. The acute effects of current available effective antidepressants include blocking selective serotonin or noradrenaline reuptake, alpha2 autoreceptors or monoamine oxidase. Although efficacious, current treatments often produce partial or limited symptomatic improvement rather than remission. While current pharmacotherapies target monoaminergic systems, distinct neurobiological underpinnings and other systems are likely involved in the pathogenesis of depression. Recently, several promising hypotheses of depression and antidepressant action have been formulated. These hypotheses are largely based on dsyregulation of neural plasticity, CREB, BDNF, corticotropin-releasing factor, glucocorticoid, hypothalamic-pituitary adrenal axis and cytokines. Based on these new theories and hypotheses of depression, a number of new and novel agents, including corticotropin-releasing factor antagonists, antiglucocorticoids, and substance P antagonists show a considerable promise for refining treatment options for depression. In this article, the current available pharmacotherapies, current understanding of neurobiology and pathogenesis of depression and new and promising directions in pharmacological research on depression will be discussed.

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Inhibitory Activity on Monoamine Oxidase of Chrysanthemum indicum L. (감국의 Monoamine Oxidase 저해활성)

  • Chang, Eun-Ju;Choi, Dong-Kug;Park, Tae-Kyu;Hwang, Keum-Hee
    • Korean Journal of Pharmacognosy
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    • v.38 no.1
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    • pp.27-30
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    • 2007
  • We examined the inhibitory activities against monoamine oxidase (MAO) of Chrysanthemum indicum L. in vitro and in vivo methods. Methanolic extract of C. indicum showed significant inhibitory activities on MAO-A that were prepared from rat brain in vitro. The inhibitory activities were measured by serotonin as a substrate. The $IC_{50}$ value of methanolic extract of C. indicum was 0.24 mg/ml for the inhibition of MAO-A. The ethylacetate fraction of methanolic extract of C. indicum exhibited the best activity toward MAO-A with $IC_{50}$ value of 0.05 mg/ml in vitro. It was observed that those activities in vivo tests have different tendency each other. Ethanolic extract of C. indicum was have no effect on rat MAO by the oral administration (p<0.05). However, MAO inhibitory activities of ethanolic extract of C. indicum by the oral administration have similar tendency to those of iproniazid. Consequently, we suggest that C. indicum may have the effects on the inhibitory activities against MAO both in vitro and in vivo. These results indicates that the C. indicum extract has properties indicative of potential neuroprotective ability.

Erratum

  • 대한한방신경정신과학회
    • Journal of Oriental Neuropsychiatry
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    • v.24 no.3
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    • pp.321-330
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    • 2013
  • Voice Handicap Index and Voice-Related Quality of Life in Idiopathic Parkinson's Disease 10.7231/jon.2013.24.2.155, The Differences of Learning Characteristics in Sasang Constitution 10.7231/jon.2013.24.2.163, A Preliminary Comparison of the Efficacy of Auricular Acupuncture, Transdermal Nicotine Patch and Combination Therapy for Smoking Cessation 10.7231/jon.2013.24.2.179, The Effects of OnDam-tang-Kami-bang (ODK) in Antioxidant and Serotonin Metabolism Testing on P815 Cell 10.7231/jon.2013.24.2.189