• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.37-46
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• 2001

Whenever a clinician manages the patients with depression, he may meet various problems that make it difficult to treat them. Even though he has good skills and knowledge about depression, some barriers will be appear during his practice. In general, the difficulties in treating depression are treatment-resistance, adverse effects of antidepressants, pregnancy in female patients, comorbid medical conditions, poor compliance, drug-drug interactions, and so on, which are related with pharmacological treatments. Here, only the two of them, the treatment-resistant depression and difficult problems concerned with pregnancy, were discussed. Some level of treatment resistance is the norm rather than the exception. As the treatment failure stems from inadequate treatment, it is important that the clinician should prescribe medications with sufficient doseage and adequate duration. And to overcome the treatment resistant depression the polypharmacy is necessary, in that case, the side effects and toxicities should be explored and managed immediately. So the clinician have to learn more about the pharmacokinetic and pharmacodynamic mechanisms of each drugs used in treatment of depression. When the risk of the fetus by the exposure is higher than the risk of untreated maternal psychiatric disorder, psychotropic medications should be used during pregnancy. Women who are maintained on psychotropics and become pregnant, as well as women with the new onset of psychiatric symptoms during pregnancy, should be carefully reassessed. However, data concerning the potential risk of long-term behavioral changes following prenatal exposure to psychotropics is rare, so further longitudinal follow-up studies are needed.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.9-15
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• 2007

Purpose: Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Materials and Methods: Twelve patients with drug-resistant depression (7 male, 5 female; age range: $19{\sim}52$ years; mean age: $29.3{\pm}9.3$ years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected p<0.01, voxel=100). Results: Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in: the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Conclusion: Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant depressed patients.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.161-167
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• 2023

Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.

• Mood & Emotion
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• v.16 no.3
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• pp.140-151
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• 2018

Objectives : The purpose of this study was to examine effects of adjunctive aripiprazole versus bupropion, on depressive symptoms of female depression. Methods : Sixty six female patients with major depressive disorders were enrolled from a six-week, randomized prospective open-label multi-center study. Participants were randomized to receive aripiprazole (2.5-10 mg/day) or bupropion (150-300 mg/day). Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale (HAM-D17), Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores, and Clinical Global Impression-Severity (CGI-S) were obtained at baseline and after one, two, four, and six weeks. Changes on individual items of HAM-D17 were assessed as well as on composite scales (anxiety, insomnia and drive), and on four core subscales that capture core depression symptoms. Results : Overall, both treatments improved depressive symptoms, without causing serious adverse events. There were significant differences in the HAM-D17 total score (p=0.046) and CGI-S (p=0.004), between aripiprazole and bupropion augmentation, favoring aripiprazole over bupropion. Aripiprazole revealed significantly greater effect size in depressed mood (p=0.006), retardation (p=0.005), anxiety psychic (p=0.032), and general somatic symptom (p=0.01). Conclusion : While both treatments were effective, results of this study suggested that aripiprazole may be preferable, in treating general and core symptoms of female depression.

• Journal of Korean Neurosurgical Society
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• v.62 no.3
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• pp.344-352
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• 2019

Epilepsy is one of the major chronic neurological diseases affecting many patients. Resection surgery is the most effective therapy for medically intractable epilepsy, but it is not feasible in all patients. Vagus nerve stimulation (VNS) is an adjunctive neuromodulation therapy that was approved in 1997 for the alleviation of seizures; however, efforts to control epilepsy by stimulating the vagus nerve have been studied for over 100 years. Although its exact mechanism is still under investigation, VNS is thought to affect various brain areas. Hence, VNS has a wide indication for various intractable epileptic syndromes and epilepsy-related comorbidities. Moreover, recent studies have shown anti-inflammatory effects of VNS, and the indication is expanding beyond epilepsy to rheumatoid arthritis, chronic headaches, and depression. VNS yields a more than 50% reduction in seizures in approximately 60% of recipients, with an increase in reduction rates as the follow-up duration increases. The complication rate of VNS is 3-6%, and infection is the most important complication to consider. However, revision surgery was reported to be feasible and safe with appropriate measures. Recently, noninvasive VNS (nVNS) has been introduced, which can be performed transcutaneously without implantation surgery. Although more clinical trials are being conducted, nVNS can reduce the risk of infection and subsequent device failure. In conclusion, VNS has been demonstrated to be beneficial and effective in the treatment of epilepsy and various diseases, and more development is expected in the future.

• Korean Journal of Biological Psychiatry
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• v.24 no.4
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• pp.167-174
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• 2017

Based on advances in biotechnology and neuroscience, neuromodulation is poised to gain clinical importance as a treatment modality for psychiatric disorders. In addition to old-established electroconvulsive therapy (ECT), clinicians are expected to understand newer forms of neurostimulation, such as deep brain stimulation (DBS), vagus nerve stimulation (VNS), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). Given the growing interest in non-invasive neuromodulation technologies, clinicians may seek sufficient information about neuromodulation to inform their clinical practice. A growing literature suggests that applications of non-invasive neuromodulation have evidence particularly for indications where treatments are currently insufficient, such as drug-resistant depression. However, positive neuromodulation studies require replication, and the precise interactions among stimulation, antidepressant medication, and psychotherapy are unknown. Further studies of long-term safety and the impact on the developing brain are needed. Non-invasive neuromodulatory devices could enable more individualized treatment. However, do-it-yourself (DIY) stimulation kits require a better understanding of the effects of more frequent patterns of stimulation and raise concerns about clinical supervision, regulation, and reimbursement. Wide spread enthusiasm for therapeutic potential of neuromodulation in clinical practice settings should be mitigated by the fact that there are still research gaps and challenges associated with non-invasive neuromodulatory devices.

• Korean Journal of Veterinary Service
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• v.22 no.4
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• pp.325-347
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• 1999

This study was conducted to investigate the epidemiological, clinicopathological, microbiological, pathological observations and other tests from sudden death in feedlot cattle at the region of Sarari in Korea during the period from 1994 to 1999. Massive or sporadic occurrence of sudden death has been observed in 101 heads of 47 farmhouse. There were 20.8% in spring, 29.7% in summer, 16.8% in autumn, 32.7% in winter, and 62.3% in reproductive, 27.7% in growing, 5.0% in beef cattle, 5.0% in calf in prevalence of sudden death in cattle. Enterotoxemia(88.0%), pneumonia(3.5%), intestinal diarrhea(3.5%), liver abscess(1.5%) and indigestion(1.5%) were detected from 67 heads of sudden death cattle. In clinical observations, cattle were generally died of sudden recumbency with convulsions followed anorexia, depression, ataxia, muscular tremor, tachycardia and dyspnea without any premonitory symptoms. Epidemiological surveys showed no evidence that other factors such as pesticide, insecticide, fertilizer, chemical drug3 and those of others caused sudden death. Macroscopically, there were coagulation disorders of blood, congestion, edema and haemorrhage of lung, congestion and haemorrhages, watery and blood-tinged contents of small intestine. Histopathologically, we observed pulmonary congestion and haemorrhage, necrotic intestinal mucosa accompanied with haemorrhage and congestion, and also increased globule leukocytes between bronchial epithelia with mild pneumonia. Clinicopathologically, only elevation of blood glucose and aspartate aminotransferase(AST) was detected. Magnesium and calcium deficiency were not detected, but parasites were detected highly in normal and dead cattles. Microbiologically, Clostridium(Cl) pefringens were detected from small intestinal contents of 94% (63/67) of sudden death cattle and 51%(51/101) of slaughter cattle, and the population were $10^{6-8}$/cfu/$m\ell$ after 16~32 hours. Consequently, it was proved that the cause of death in cattle was enterotoxemia. Pathogenic test of mouse and goat inoculated with Cl perfringens type A toxin has been demonstrated as similar observation to natural cases. In antimicrobial susceptibility test, ampicillin, bacitracin, polymycin, cephalothin, penicillin, choramphenicol, erythromycin, tetracycline were highly susceptible, and amikacin, gentamicin, kanamycin, neomycin, streptomycin, sulfamethoxine, sulfamethazine were resistant. Cl perfringens were resisted for 4 hours in 3% formalin, 20 minutes in 4% phenol, 20 minutes in 0.5% mercuric chloride and 40 minutes in 0.1% sodium hydroxide, respectively. The useful method to prevent from occurrance of enterotoxemia in feedlot cattle was a dietary administration of antibiotics and miyari acid.