• Korean Journal of Biological Psychiatry
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• v.9 no.1
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• pp.34-41
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• 2002

Background:Since serotonin neurotrasnmission plays an important role in the pathophysiology of depression, the drug that acts on serotonin transporter can be an effective antidepressant. The aim of this study was to investigate the relationship between serotonin transporter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. Method:The 175 depressive patients, who met DSM-IV criteria for major depressive disorder or dysthymic disorder were enrolled into three year study. The genotypes of the patients were investigated by polymerase chain reaction of genomic DNA with promoter regions of the serotonin transporter gene. The patients were assessed by the Clinical Global Impression Scale, at the 1st visit, 8th week, 16th week, 1st year, 2nd and 3rd year after the antidepressant treatment. Result:The genotypes of 138 patients were investigated and 128 of them finished this 1st year study and 107 remained in the study after 2-year treatment, and, 97 completed this 3-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 antidepressant therapeutic response than heterozygote(l/s). The heterozygote(l/s) showed a better response than the subset with homozygote(s/s) of short variant at 1st, 2nd and 3rd year after the antidepressant treatment in CGI-global improvement score. Conclusion:This result shows that the serotonin transporter polymorphism may be related to the long-term effect of antidepressant treatment and there may be also ethnic difference.

• Korean Journal of Biological Psychiatry
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• v.15 no.3
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• pp.175-185
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• 2008

Accumulating evidence has suggested the existence of reciprocal communication between immune, endocrine, and neurotransmitter system. Cytokine hypothesis of depression implies that increased pro-inflammatory cytokine such as -1, IL-6, IL-12, TNF-${\alpha}$, and IFN-${\gamma}$ in major depression, acting neuromodulators, play a key role in the mediation of behavioral, neuroendocrine, and neurochemical disturbances in depression. Concerning the relation between cytokines and serotonin metabolism, pro-inflammatory cytokines have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase(IDO) that metabolizes tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The neurodegeneration process is reinforced by the neurotoxic effect of the hypercortisolemia during depression. From this perspective, it is possible that efficacy of antidepressants in the treatment of depression may, at least in part, rely on downregulation of pro-inflammatory cytokine synthesis. So, the use of cytokine synthesis inhibitors or cytokine antagonists may be a new treatment approach in depression. However, at present the question whether cytokines play a causal role in the onset of depression or are mere epiphenomena sustaining depressive symptoms remains to be elucidated. Nevertheless, cytokine hypothesis has created new perspectives in the study of psychological and pathophysiological mechanism that are associated with major depression, as well as the prospect for developing a new generation antidepressants.

• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.22-29
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• 1996

The introduction of chlorpromazine in the 1950's revolutionized the treatment of schizophrenia and ultimately led to the development of selective $D_2$ antagonists such as haloperidol, a goal in keeping with the prevalent theories at that time. However, limitations in the efficacy of these agents, a growing awareness of their side effects, and theoretical shifts in our understanding of schizophrenia have encouraged ongoing efforts to develop better 'atypical' antipsychotics. Clozapine, and subsequently risperidone, represent examples of these novel compounds, both of which incorporate shared serotonin-dopamine antagonism(SDA). The next years will be dominated by further development of SDA compounds, although a number of other lines of investigation are also being pursued.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.113-117
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• 2005

Background: Serotonin 3 receptor is involved in the modulation of nociceptive transmission in the spinal cord. The serotonin 3 receptor antagonist has been used for the management of opioid-induced nausea and vomiting. The aim of this study was to examine whether the analgesic effect of morphine is antagonized by serotonin 3 receptor antagonists at the spinal level. Methods: Rats were implanted with lumbar intrathecal catheters. For nociception, a formalin solution (5%, $50{\mu}l$) was injected into the hind paw of male Sprague-Dawley rats. To determine whether the effect of intrathecal morphine was mediated via serotonin 3 receptors, serotonin 3 receptor antagonists were intrathecally administered 10 min prior to the morphine delivery. Following the formalin injection, formalin-induced nociceptive behavior (flinching response) was observed for 60 min. Results: Intrathecal morphine produced a dose-dependent suppression of the flinches in both phases during the formalin test. The analgesic action of morphine was not reversed by serotonin 3 receptor antagonists (LY-278,584, ondansetron), which had little per se effect on the formalin-induced nociception. Conclusions: Spinal serotonin 3 receptors may not be involved in the analgesia of morphine on a nociceptive state evoked by a formalin stimulus.

• Anxiety and mood
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• v.3 no.1
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• pp.20-25
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• 2007

The definite causes of obsessive-compulsive disorder (OCD) are still unknown. OCD has been suggested to be related to many neurotransmitters in brain, such as serotonin, dopamine and glutamate. It has been shown that serotonergic neurons play a crucial role in the pathophysiology of OCD. Recently, it is known that neurotransmitters other than serotonin also play a role in the pathophysiology of OCD, and a series of studies have provided a few evidence that glutamate may be involved in some OCD patients. The purpose of this article was to review the literatures on glutamatergic dysfunction in OCD. We suggest that glutamatergic dysfunction may be implicated in the pathophysiology of OCD.

• Korean Journal of Biological Psychiatry
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• v.5 no.2
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• pp.278-282
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• 1998

Various neurotransmitters have been proposed as possible mediators of penile erection. Especially, norepinephrine and serotonin might have a important role in sexual arousal and penile erection. And it could be hypothesized that the psychogenic impotence is associated with the depletion or imbalance of norepinephrine and serotonin from evidences, such as the symptomatic manifestation of depression and the antidepressantinduced sexual dysfunction. The authors investigates the association of norepienphrine and serotonin with psychogenic impotence. The psychogenic impotent group(PIG) consisted of twenty-three patients with psychogenic impotence and the controlled group(CG) consisted of twenty-seven patients without psychogenic impotence. PIG had no organic cause accounting for their erectile dysfunction. The Beck Depression Inventory(BDI) and the State-Trait Anxiety Inventory(STAI) were applied to each subject to assess mood, state anxiety(SA) and trait anxiety(TA). Plasma norepinephrine level from systemic blood and 5-hydroxyindoleacetic acid(HIAA) levels from 24-hours urine were measured in each subject. The mean score of BDI of PIG was significantly higher than that of CG(p=0.015). PIG had a tendency of higher TA compared with CG(p=0.054). And also SA was higher in PIG, but did not show significant difference(p=0.193). The level of norepinephrine was significantly lower in patient with psychogenic impotence(p=0.000). And the level of 24-hours urine 5-HIAA was lower in PIG but did not show significant difference(p=0.494). Although the authors did not exclude depressive disorders in PIG, the present findings suggest that psychogenic impotence might have higher depressive mood and trait anxiety, and be associated with the depletion of norepinephrine in systemic blood.

• Food Science and Biotechnology
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• v.16 no.1
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• pp.71-77
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• 2007

The antioxidant properties of twelve phenolic compounds, including matairesinol 4'-O-$\beta$-D-glucoside, 8'-hydroxyarctigenin 4'-O-$\beta$-D-glucoside, matairesinol, 8'-hydroxyarctigenin, N-feruloylserotonin 5-O-$\beta$-D-glucoside, N-(p-coumaroyl)-serotonin-5-O-$\beta$-D-glucoside, N-feruloylserotonin, N-(p-coumaroyl)serotonin, luteolin 7-O-$\beta$-D-glucoside, luteolin, acacetin 7-O-$\beta$-glucuronide, and acacetin, isolated from defatted safflower (Carthamus tinctorius L.) seeds were evaluated with regard to the DPPH, superoxide and hydroxyl radicals. Additionally, levels of phenolic compounds were determined by HPLC in two cultivars of safflower seeds. Among them, four serotonin derivatives showed potent DPPH ($IC_{50}=10.83-21.75\;{\mu}M$) and hydroxyl ($IC_{50}=75.93-374.63\;{\mu}M$) radical scavenging activities, and their activities were significantly stronger than that of ${\alpha}-tocopherol$. Four flavonoids ($IC_{50}=170.65-275.83\;{\mu}M$) and four lignans ($IC_{50}=114.22-406.10\;{\mu}M$) exhibited significant superoxide and hydroxyl radical scavenging activities, respectively, whereas these compounds contained less activity toward the DPPH and hydroxyl radicals than serotonin derivatives. The levels of serotonin derivatives, lignans and flavonoids in safflower seeds of two cultivars ranged from 49.30 to 260.40, 3.72 to 158.90, and 11.72 to 214.97 mg% (dry base), respectively. Of the two cultivars, 'Cheongsu' had somewthat higher concentrations of phenolic compounds than 'Uisan'. These results suggest that phenolic compounds in safflower seeds may playa role as protective phytochemical antioxidants against reactive oxygen-mediated pathological diseases.

• The Korean Journal of Pharmacology
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• v.19 no.2
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• pp.45-55
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• 1983

A role for brain serotonin(5-HT) in regulation of the HPA axis has been suggested but remains contoversial and poorly defined. The present experiments were designed to check kinetic parameters of 5-HT turnover in rat hypothalamus and remainder brain areas before and after stress and to test whether using various different pharmacologic approaches to stimulate or eliminate the control serotonergic system have any consistent effect on the stress-induced activation of HPA system. Steady state brain serotonin and 5-HIAA concentrations during 1 min ether stress were significantly elevated without significant rise in the levels of plasma corticosterone, which highly increased 2 minutes after stress. This suggests that the increase in serotonergic neuron activity precede that in HPA activity. Furthermore, during 1 ruin-ether stress or 30 min immobilization stress there is a marked increase in hypothalamic and remainder brain serotonin (5-HT) turnover or synthesis rates assessed by both the pargline/5-HT method and pargyline/5-HIAA method. The stress-induced corticosterone levels were increased by serotonin precursors and serotonin agonist in a dose-related fashion. The stress- induced corticosterone levels were highly elevated by L-tryptophan (100 mg/kg) and Potentiated by monoamine oxidase inhibitor, pargyline or serotonin agonist, 5-MeoDMT. The stress-induced elevation of corticosterone and 5-HT levels in rat brain were not significantly decreased by the administration of 5-HT synthesis inhibitor, PCPA and 5-HT neurotoxin, 5,7-DHT. However, the stress-induced elevation of corticosterone and 5-HT levels were decreased by the destruction of midline raphe nuclei. There was a strong positive correlation between plasma corticosterone and 5-HT concentrations changed by drugs which mainly manipulating 5-HT system in the hyhothalamus and in the remainder of the brain. In conclusion, our present data stongly suggest that 5-HT is an important key neurotransmitter involved in the stress-induced activation of the HPA system.

• Korean Journal of Biological Psychiatry
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• v.6 no.1
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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.

• Korean Journal of Pharmacognosy
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• v.30 no.2
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• pp.145-150
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• 1999

To explain the theory of KIMI which is the theory of therapeutics in oriental medicine, monoamine oxidase(MAO) activities were measured in the brain and liver of mice which were orally administered oriental medicinal herbs which were classified into cold and hot drugs. Rheum palmatum, Anemarrhena asphodeloides, Gardenia jasminoides, Scutellaria baicalensis and Coptis japonica were considered as the cold drugs and Zingiber officinale, Aconitum carmichaeli, Asiasarum sieboldi, Evodia officinalis and Cinnamomum cassia were included in the hot drugs. The effects of cold and hot drugs on in vitro enzyme activities were measured and compared with the in vivo effects. Serotonin is important neurotransmetter involved in the control of body temperature. The MAO plays a central role in the metabolism of many neurotransmetter monoamines including serotonin. MAO is a flavoprotein found exclusively in the mitochondrial outer membrane, occuring in the MAO-A and MAO-B subtypes. MAO-A deaminates serotonin and noradrenaline, whereas MAO-B prefers phenylethylamine and benzylamine as substrates. Coptis japonica and Aconitum carmichaeli elevated the in vivo MAO activities and especialy, in vivo MAO-B activities were significantly increased. In vitro MAO-A activities were increased by hot drugs, whereas the in vitro MAO-B activities were inhibited. Cold drugs inhibited both enzyme activities in vitro.