• 생물정신의학
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• 제8권2호
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• pp.226-232
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• 2001

The pharmacotherapy of depression has reduced morbidity and improved outcome for many depressive patients. A wide range of classical and new antidepressants are available for their treatment. However, 30-40% of all patients do not respond sufficiently to the initial treatment and present adverse effects. Pharmacogenetics studies the genetic basis of an individual's ability to respond to pharmacotherapy. Recently, some reports on serotonin transporter gene polymorphisms and their influence on the response to antidepressive therapy provide an interesting diagnostic tool in assessing the chances of response to antidepressants. We also investigated the relationship between serotonin transprter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. 128 depressive patients were enrolled into 2nd year study. The therapeutic response of each subset was not different at 8th, 16th week, but the subset with homozygote(l/l) of long variant showed a better therapeutic response to antidepressant than the heterozygote(l/s) of long and short variant, which showed a better therapeutic response than the subset with homozygote (s/s) of short variant at 1st year and 2nd year after the antidepressant treatment. This result shows that the serotonin transporter polymorphisms may be related to the long-term effect of antidepressant treatment. The potential for pharmacogenomics, the use of genetic information to guide pharmacotherapy and improve outcome by providing individualized treatment decisions, has gained increasing attention. pharmacogenomics will contribute to individualize drug choice by using genotype to predict positive clinical outcomes, adverse reactions, and levels of drug metabolism. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual molecular profile, will impact the antidepressant therapy and this approach will replace the traditional trial-and-error practice of medicine.

• BMB Reports
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• 제39권4호
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• pp.383-393
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• 2006

Little is known concerning the mechanisms responsible for the transplacental transfer of thiamine. So, the aim of this work was to characterize the placental uptake of thiamine from the maternal circulation, by determining the characteristics of $^3H$-thiamine uptake by a human trophoblast cell line (BeWo). Uptake of $^3H$-thiamine (50-100 nM) by BeWo cells was: 1) temperature-dependent and energy-independent; 2) pH-dependent (uptake increased as the extracellular medium pH decreased); 3) $Na^+$-dependent and $Cl^-$-independent; 4) not inhibited by the thiamine structural analogs amprolium, oxythiamine and thiamine pyrophosphate; 5) inhibited by the unrelated organic cations guanidine, N-methylnicotinamide, tetraethylammonium, clonidine and cimetidine; 6) inhibited by the organic cation serotonin, and by two selective inhibitors of the serotonin plasmalemmal transporter (hSERT), fluoxetine and desipramine. We conclude that $^3H$-thiamine uptake by BeWo cells seems to occur through a process distinct from thiamine transporter-1 (hThTr-1) and thiamine transporter-2 (hThTr-2). Rather, it seems to involve hSERT. Moreover, chronic (48 h) exposure of cells to caffeine ($1\;{\mu}M$) stimulated and chronic exposure to xanthohumol and iso-xanthohumol (1 and $0.1\;{\mu}M$, respectively) inhibited $^3H$-thiamine uptake, these effects being not mediated through modulation of the expression levels of either hThTr-1 or hSERT mRNA.

• Biomolecules & Therapeutics
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• 제30권2호
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• pp.191-202
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• 2022

Tetrazoles were designed and synthesized as potential inhibitors of triple monoamine neurotransmitters (dopamine, norepinephrine, serotonin) reuptake based on the functional and docking simulation of compound 6 which were performed in a previous study. The compound structure consisted of a tetrazole-linker (n)-piperidine/piperazine-spacer (m)-phenyl ring, with tetrazole attached to two phenyl rings (R1 and R2). Altering the carbon number in the linker (n) from 3 to 4 and in the spacer (m) from 0 to 1 increased the potency of serotonin reuptake inhibition. Depending on the nature of piperidine/piperazine, the substituents at R1 and R2 exerted various effects in determining their inhibitory effects on monoamine reuptake. Docking study showed that the selectivity of tetrazole for different transporters was determined based on multiple interactions with various residues on transporters, including hydrophobic residues on transmembrane domains 1, 3, 6, and 8. Co-expression of dopamine transporter, which lowers dopamine concentration in the biophase by uptaking dopamine into the cells, inhibited the dopamine-induced endoctytosis of dopamine D₂ receptor. When tested for compound 40 and 56, compound 40 which has more potent inhibitory activity on dopamine reuptake more strongly disinhibited the inhibitory activity of dopamine transporter on the endocytosis of dopamine D₂ receptor. Overall, we identified candidate inhibitors of triple monoamine neurotransmitter reuptake and provided a theoretical background for identifying such neurotransmitter modifiers for developing novel therapeutic agents of various neuropsychiatric disorders.

• 동의생리병리학회지
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• 제27권4호
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• pp.422-430
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• 2013

This experiment was designed to investigate the effects of So-Oochim-tang-Gagam-bang (SOCT-G) on oxidative stress and serotonin metabolism in P815 Mast Cells The effects of SOCT-G on activity of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging and Super Oxide Dismutase (SOD) in P815 mast cells were investigated. The effect of SOCT-G on content of serotonin in P815 mast cells was investigated. The effects of SOCT-G on expression of 5-hydroxytryptamine transporter (5-HTT), Tryptophan hydroxylase 1 (TPH-1) mRNA in P815 mast cells were investigated. The SOCT-G increased DPPH radical-scavenging activity in P815 mast cells. The SOCT-G increased SOD activity in P815 mast cells. The SOCT-G decreased the intracellular content of serotonin in P815 mast cells. The SOCT-G decreased 5-HTT and TPH-1 mRNA expression in P815 mast cells. This experiment shows that So-Ochm-Tang-Gagam-bang has a significant effect of oxidative stress that help prevent free radical damage. And So-Ochim-Tang-Gagam-bang decreased the intracellular content of serotonin and mRNA expression of 5-HTT and TPH-1. Therefore, further researches are suggested to reveal the anti-depressive effectiveness of So-Ochim-Tang-Gagam-bang.

• 감성과학
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• 제10권2호
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• pp.243-252
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• 2007

효모 (Saccharomyces cerevisiae)는 인체에 무해한 Generally Recognized As Safe(GRAS)급으로 인정되며, 최근 효모 추출물이 정신적 긴장, 과민, 두통 같은 월경 전 증후군을 완화시키는 효과가 있음이 보고되어 있어, 효모추출물(Saccharomyces cerevisiae extract: SCE)과 그 분획(SCE-40)이 우울증과 불안증에서도 효과가 있는지 확인하고자 다음 실험을 실시하였다. 행동학적 검정으로 SCE의 항우울 효과를 확인하기 위해 SCE를 0, 1, 10, 100mg/kg의 농도로 웅성 ICR 생쥐에게 2주간 경구 투여한 후 강제수영검사(forced swimming test; FST)에서의 부동시간과, 또 다른 항우울 효과 검정 실험인 미현수검사(Tail Suspension Test: TST)에서의 부동시간을 측정하였다. 또한, SCE의 항불안 효과 검정을 위해서 SCE를 0, 1, 10, 100mg/kg의 농도로 웅성 ICR 생쥐에게 1회(1시간 전), 혹은 2주간 경구 투여한 후 고위십자미로검사(Elevated-plus-maze test : EPM)에서의 open arms에 머문 시간을 측정하였다 시험관내 실험으로는 웅성 백서의 대뇌피질에서의 SCE 및 SCE-40의 serotonin transporter (SERT), norepinephrine transporter(NET), 그리고 GABA의 ligand의 결합 억제능 측정과, serotonin (5-hydroxytryptamine: 5-HT), norepinephrine uptake 측정이 수행되었다. 행동적 실험 결과, FST에서 1회나 2주간 SCE 10mg/kg과 100mg/kg을 투여 받은 생쥐에서 생리 식염수만 투여 받은 생쥐보다 부동시간이 유의하게 감소됨을 보여 SCE에 의해 항우울 효과가 유발됨을 보였고, TST 실험에서도 유사한 결과가 나타났다. 또한, 항불안을 측정하는 EPM 실험에서도 1회나 2주간 SCE 10mg/kg과 100mg/kg을 투여 받은 생쥐에서 생리 식염수만 투여 받은 생쥐보다 open arms에서 머무는 시간이 유의하게 증가되어 SCE가 단기 또는 장기간의 항불안에 효과가 있음을 나타냈다. 시험관내 실험 결과에서는, SCE와 SCE-40이 SERT, NET, 그리고 GABA ligand의 결합 억제능이 있음이 확인되었고, SCE와 SCE-40은 serotonin(5-hydroxytryptamine: 5-HT)과, norepinephrine의 uptake를 억제하는 것으로 나타났다. 그러므로 본 연구는 효모 추출물(SCE)과 그 분획(SCE-40)이 행동적, 신경학적으로 항우울, 항불안에 효과가 있음을 확인하였으며, 효모 추출물(SCE)과 그 분획(SCE-40)이 안전한 천연식품으로서 우울증, 불안증 등의 관련 질환의 예방, 치료용 의약품 개발과 기능성 식품에 효과적으로 이용될 수 있음을 시사한다.

• 생물정신의학
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• 제16권1호
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• pp.25-36
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• 2009

Objectives : The aim of this study was to investigate the association between Korean ADHD patients and the l/s polymorphism of serotonin transporter(5-HTTLPR). Methods : The study sample consisted of 189 Korean ADHD children diagnosed by Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version(K-SADS-PL), both parents of ADHD children, and 150 normal children. DNA were extracted from the blood of all samples, and genotyping was done. Based on the allele and genotype information, not only the case-control analysis between ADHD and normal children but also the family-based association test among ADHD children and their parents. Transmission disequilibrium test(TDT) were performed for family-based associated test(number of trio=113). The results of the clinical rating and neuropsychological tests were compared according to the l/s genotype of ADHD children. Results : In case-control analysis, there were no statistically significant difference of l/s gene polymorphism between ADHD and normal children in various kinds of analysis condition. In family-based association study, TDT failed to detect linkage disequilibrium between l/s gene polymorphism and ADHD in whole ADHD families. However, in the families of ADHD inattentive type only(number of trio=23), I allele was transmitted more preferentially in the proband with ADHD even if the number of families was small(${\chi}^2$=4.57, p=.032). In the analysis of the results from the clinical scales and neuropsychological tests in ADHD children, the score of the Novelty- Seeking of ADHD children with l/l genotype was significantly lower than with the other genotypes(F=3.15, p=.047), and that of Self Transcendence was significantly higher(F=4.25, p=.017). Conclusion : The results of this study suggest there were no significant genetic association between the 5- HTTLPR gene polymorphism and Korean ADHD.

• 한국산업보건학회지
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• 제21권2호
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• pp.116-122
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• 2011

Human occupational exposure to n-hexane has been associated with neurobehavioral symptoms such as depression, irritablity, acute irritation symptom, concentration disturbance and fatigue. Effects of monoamine oxidase (MAO) B and serotonin transporter receptor (5-HTTR) polymorphisms on the neurobehavioral symptoms were investigated in 70 male workers from TV and computer monitor manufacturing plants exposed to n-hexane. Neurobehavioral symptoms were assessed through a self-reported questionnaire and ambient level of n-hexane was measured by NIOSH method. Blood and urine were collected from each workers to determine the MAO(B), 5-HTTR and urinary 2,5-hexanedione(2,5-HD). The mean concentration of volatile n-hexane was $18.8{\pm}28.8ppm$ and that of urinary 2,5-HD was $1.07{\pm}1.47mg/g$ creatinine. Statistically significant associations with sexual disturbance were age and smoking. The frequencies of MAO(B) AA, AG and GG were 18.6%, 45.7% and 35.7%, respectively, and the frequencies of 5-HTTR ll, ls and ss genotype were 82.9%, 15.7% and 1.4%, respectively. MAO (B) gene polymorphisms had susceptibility to the neurobehavioral symptoms such as fatigue, concentration disturbance, irritability and acute irritation symptom and 5-HTTR gene polymorphism had susceptibility to the sleep disturbance and acute irritation symptom. On multiple logistic regression analysis for the neurobehavioral symptoms, memory disturbance was significantly associated with smoking(OR=6.752, 95% CI=37.46) and drinking(OR=4.033, 95% CI=1.252-12.98), emotional lability was MAO(B) genotype(OR=0.412, 95% CI=0.170-0.996), fatigue (OR=1.011, 95% CI=1.000-1.021) and acute irritation(OR=0.990, 95% CI=0.981-1.000) were working duration and sexual disturbance were significantly associated with age(OR=1.208, 95% CI=1.042-1.399), ambient n-hexane(OR=1.077, 95% CI=1.005-1.154) and 2,5-HD(OR=0.186, 95% CI=0.041-0.841). This finding implies that the MAO (B) and 5-HTTR polymorphisms may affect susceptibility for specific neurobehavioral symptoms associated with n-hexane exposure in workers.

• Bulletin of the Korean Chemical Society
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• 제25권6호
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• pp.895-899
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• 2004

We have designed a new family of radioligands, 3-(amino- and hydroxymethyl)-4-(5-iodopyridin-2-ylthio)indoles, combining characteristically distinct moieties proven to impart successful binding ability in a variety of structurally diverse selective serotonin reuptake inhibitors recently published. Described in this article are the syntheses of 3-substituted 4-(5-iodopyridin-2-ylthio)-indoles, featuring successful adaptation of the modified Leimgruber-Batcho indole synthesis onto the key intermediate 1-(5-iodopyridin-2-ylthio)-2-methyl-3-nitrobenzene (6) prepared from the nucleophilic aromatic substitution of chloropyridine 7 with thiophenol 8.

• 생물정신의학
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• 제6권1호
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• pp.3-11
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• 1999

At the beginning, researches on the biology of depression or affective illness have focused mainly on the receptor functions and neuroendocrine activities. And the studies of the past years did not break new theoretical background, but the recent advances in the research on the molecular mechanisms underlying neural communication and signal transduction do add some insights to many established ideas. This article will overview some of the more recent advances in the clinical researches of depression. Our major concerns to be presented here include the followings : (1) alterations in the post-synaptic neural transduction ; (2) changes in the neurons of hypothalamic neuropeptides ; (3) decreased peptidase enzyme activities ; (4) associations of hypothalamic-pituitary-adrenal axis abnormalities with serotonin neurotransmission ; (5) role of serotonin transporter ; (6) changes in the responsiveness of intracellular calcium ion levels ; (7) the inositol deficiency theory of lithium and depression ; (8) the transcription factors including immediate early genes ; (9) recent genetic studies in some families. This brief overview will suggest that changes in DNA occur during antidepressant therapy. These changes at the DNA level initiating a cascade of events underlying antidepressant modality will give us the insights on the molecular biological basis of the pathogenesis of depression and cues for a new class of antidepressants.

• 생물정신의학
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• 제12권1호
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• pp.3-12
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• 2005

Most suicides(about 90%) occur in the context of psychiatric disorders. Prediction of suicide risk in patients with mental illness is very important in preventing suicide attempts. However, current approaches to predict suicidality are based on clinical history and have low specificity and biological markers are not yet included. Many studies have explored the association between different biological parameters and suicidality. Studies of cerebro-spinal fluid(CSF) demonstrated that 5-HIAA and HVA levels were lower in patients with a history of suicide. Platelet serotonin transporter and the 5-HT2 serotonin receptor have also been studied in relation to violence and suicide. Depressive patients with greater suicidal tendency had significantly lower cholesterol concentrations but some researchers failed to find the correlation. DST non-supression is reported to predict suicidality in major depression. Several studies demonstrated a relationship between intron 7 polymorphism of tryptophan hydroxylase and suicidal behavior. Since suicide is not occurred in a single disease, the systematic and comprehensive study in large samples with various diagnoses is necessary to find the biological and genetic predictors of suicidal behavior.