• 생물정신의학
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• 제18권4호
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• pp.169-175
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• 2011

Stress, a risk factor of major depression induces cytokine mediated inflammation and decreased neurogenesis. In patients with major depression, significant increases of pro-inflammatory cytokines have been consistently reported. The pro-inflammatory cytokines can stimulate the hypothalamic-pituitary-adrenal (HPA) axis to release glucocorticoids. In the brain, microglia and play a role of immune activation in response to stress. Increased pro-inflammatory cytokine play a role in restricting neurogenesis in the brain. Although neurogenesis may not be essential for the development of depression, it may be required for clinically effective antidepressant treatment. Hence, stimulation of neurogenesis is regarded as a promising strategy for new antidepressant targets. This review introduces changes in neurotransmitter, cytokine and neurogenesis in major depression and explores the possible relationship between pro-inflammatory cytokines and neurogenesis related to stress in major depression.

• 여성건강간호학회지
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• 제21권2호
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• pp.106-114
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• 2015

Purpose: The purpose of this review was to describe a psychoneuroimmunology (PNI) framework for postpartum depression (PPD) and discuss its implications for nursing research and practice for postpartum women. Methods: This study explored the role of hypothalamic-pituitary-adrenal (HPA) axis and inflammation as possible mediators of risk factors for PPD through literature review. Results: From this PNI view, human bodies are designed to respond with the reciprocal interactions among the neuro-endocrine and immune system when they are faced with physical or psychological stressors. Chronic stress induces alterations in the function of HPA axis, and a chronic low-grade inflammatory response is associated with depression. The dysfunctions of cytokines and HPA axis have been observed during the postpartum period. Stress promotes glucocorticoid receptor resistance, which can promote inflammatory responses. This, in turn, can contribute to the pathophysiology of depression. This can especially affect populations at vulnerable time-points, such as women in the postpartum. Conclusion: From a PNI perspective, well-designed prospective research evaluating the role of stress and inflammation as an etiology of PPD and the effect of stress reduction is warranted to prevent PPD.

• Perspectives in Nursing Science
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• 제2권1호
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• pp.37-47
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• 2005

Biobehavioral nursing research is focused on generating knowledge that examines relations among biological, behavioral, and social dimensions of health to improve outcomes. In this paper we review the findings of a biobehavioral nursing study of individuals with fibromyalgia (FM) that was framed from the perspective of an individual human response model, the FM literature, and our previous studies in midlife women. We were particularly interested in the studying the role of 'arousal' secondary to pain or to dysregulated hypothalamic-pituitary-adrenal (HPA) axis hormones during sleep and the impact on symptom expression. Unexpectedly, we did not find evidence of, arousal' or abnormal amounts of HPA axis hormones but we did find reduced amounts of growth hormone (GH) and prolactin (PRL) and of sleep spindle activity, a biomarker of sleep maintenance. We discuss these new findings and how our thinking was re-shaped to better understand the role that disturbed sleep plays in symptom expression in FM. It is argued that disturbed sleep maintenance mechanisms coupled with dysregulated somatotrophic-growth hormone axis and sleep-related PRL render individuals vulnerable to the development of or exacerbations of FM symptoms.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제13권1호
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• pp.3-14
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• 2002

아동에 가해지는 정신적 외상의 충격은 아동의 심리발달에 지울 수 없는 상처를 남김으로써 향후 심각한 정신장애를 일으키는 결정적 원인이 된다. 아동기 외상의 현상학적 특징과 외상에 관여하는 신경생물학적 기전을 살펴보았고, 아동기에 경험하는 외상이 인격의 발달에 미치는 영향과 그와 관련한 정신병리를 알아보았다. 외상에 노출된 아동은 공통적으로 자신이 경험한 공포사건을 시각적으로 재경험하거나 그 기억을 반복하며, 놀이나 행동을 통해서도 외상사건을 반복하려는 경향을 보인다. 일회의 충격적 사건에 노출된 아동은 사건에 대한 지나친 기억과 집착을 보이고 지각왜곡이 심한 반면 장기간 반복되는 외상을 경험하는 아동은 정신적 무감각과 자기최면, 해리, 분노의 경향이 두드러진다. 소아·청소년에서는 외상 후 퇴행이 보다 현저하고 시간감각의 왜곡이 더 심하게 나타나며 아동의 연령이 어릴수록 자율신경계의 반응성이 증가하는 경향을 보인다. 외상적 충격에 노출되면 뇌내에서 즉각적이고 방대한 신경전달물질의 방출이 있게되는데, 자율신경계, 면역계, 시상하부-뇌하수체-부신피질 축(hypothalamic-pituitary-adrenal axis)이 활성화된다. 외상시 internal opiate가 활발한 작용을 하면서 아동으로 하여금 외상에 반응하지 않도록 하고 외상에 대한 감정반응 자체를 봉쇄할 수 있도록 해준다. 아동기 외상의 경우 central noradrenergic system에 변화가 초래되어 카테콜아민에 대해 과민감한 비정상적 소견을 보이게 된다. 체내 순환되는 cortisol 수치는 감소하고, glucocorticoid 수용체 농도와 반응성이 증가한다. 외상 후 발견되는 기억력 장애는 해마의 구조적 변화와 관련이 있는 것으로 보고되고 있다. 아동기 외상은 자기(self)와 대상(object)에 대한 내적 표상(internal representation)이 지속적으로 분화 발전하는 발달과정에서 일어난다는 점에서 인격의 발달에 심각한 영향을 미치게 된다. 해리, 신체화, 자학성, 자기애 장애의 정신병리로 발전하면서 경계성 인격장애, 자기애성 인격장애, 다중인격장애 등을 초래하게 된다.

• Clinical and Experimental Pediatrics
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• 제46권4호
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• pp.400-403
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• 2003

진단이 지연되었거나 적절하게 치료되지 않은 선천성 부신 과형성증을 가진 남아에서 장기간 고농도의 남성호르몬에 노출될 경우 처음에는 가성 성조숙증이었다가 이후 진성 성조숙증으로 전환될 수 있으므로 선천성 부신 과형성증의 조기진단과 치료가 필요하다. 저자들은 가성 성조숙증에서 진성 성조숙증으로 전환된 선천성 부신 과형성증을 가진 남아에서 hydrocortisone과 GnRH 유도체를 사용하여 큰 부작용 없이 2차 성징의 퇴축을 가져온 1례를 경험하고 문헌고찰과 함께 보고하는 바이다.

• 대한수의학회지
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• 제44권2호
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• pp.207-215
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• 2004

It is well known that the hypothalamic-pituitary-adrenocortical (HPA) axis is under the negative feedback control of adrenal corticosteroids. Previous studies have suggested that glucocorticoids can regulate neuroendocrine cells in the paraventricular nucleus (PVN) by modulating catecholaminergic transmission, a major excitatory modulator of the HPA axis at the hypothalamic level. But, the effects of corticosteroids on the expression of adrenoceptor subtypes are not fully understood. In this work, we examined mRNA levels of six adrenoceptor subtypes (${\alpha}_{1A}$, ${\alpha}_{1B}$, ${\alpha}_{2A}$, ${\alpha}_{2B}$, ${\beta}_1$ and ${\beta}_2$) in the PVN of normal and adrenalectomized (ADX) rats. Total RNA ($2.5{\mu}g$) was extracted from PVN micropunches of brain slices ($500{\mu}m$) and analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The levels of corticotropin-releasing hormone (CRH) mRNA were increased in the ADX rats relative to normal rats, indicating that the PVN had been liberated from the negative feedback of corticosteroids. Among the six adrenoceptor subtypes examined, mRNA levels for ${\alpha}_{1B}$- and ${\beta}_1$-adrenoceptors were increased, but the level for ${\beta}_2$-adrenoceptors was decreased in the ADX rats. The mRNA levels for the other three subtypes and for the general and neuronal specific housekeeping genes, glyceroaldehyde-3-phosphate dehydrogenase (GAPDH) and N-enolase, respectively, were not changed in the ADX rats. In conclusion, the results indicate that adrenal steroids selectively regulate the gene expression of adrenoceptor subtypes in the PVN.

• 한국발생생물학회지:발생과생식
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• 제15권3호
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• pp.265-272
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• 2011

It is well known that adipose tissue or body fat has been proved as a crucial component of brain-peripheral axis which can modulate the activities of reproductive hormonal axis in female mammals including rodents and human. Concerning the male reproduction, however, the role of adipose tissue has not been thoroughly studied. The present study was carried out to elucidate the effect of a high-fat (HF) diet on the reproductive system of postpubertal male rats. The HF diet (45% energy from fat, HF group) was applied to male rats from week 8 after birth for 4 weeks. The blood glucose levels, body and tissue weights were measured. Histological studies were performed to assess the structural alterations in the reproductive tissues. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus and pituitary, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Body weights (p<0.01) and blood glucose levels (p<0.01) of HF group were significantly higher than those of control animals. Similarly, the weights of epididymis (p<0.05), prostate (p<0.01), seminal vesicle (p<0.01) in HF group were higher than control levels. The weights of testis were not changed. The weights of kidney (p<0.001) and spleen (p<0.01) were significantly higher than control levels while the adrenal and pancreas weights were not changed. There were only slight alterations in the microstructures of accessory sex organs; the shape of luminal epithelial cells in epididymis from HF group were relatively thicker and bigger than those from control animals. In the semi-quantitative RT-PCR studies, the mRNA levels of hypothalamic GnRH (p<0.05) in HF group were significantly higher than those from the control animals. The mRNA levels of kisspeptin in HF group tend to be higher than control levels, the difference was not significant. Unlike the hypothalamic GnRH expression, the mRNA levels of pituitary $LH{\beta}$ and $FSH{\beta}$ were significantly decreased in HF group (p<0.05). The present study indicated that the 4-weeks feeding HF diet during the postpubertal period can alter the hypothalamus-pituitary (H-P) neuroendocrine reproductive system These results suggest that the increased body fat and the altered leptin input might disturb the H-P reproductive hormonal activities in male rats, and the changed activities seem to be responsible for the changes of tissue weights in accessory sex organs.

• The Korean Journal of Physiology and Pharmacology
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• 제17권5호
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• pp.393-403
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• 2013

Baicalein (BA), a plant-derived active flavonoid present in the root of Scutellaria baicalensis, has been widely used for the treatment of stress-related neuropsychiatric disorders including depression. Previous studies have demonstrated that repeated restraint stress disrupts the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. The behavioral and neurochemical basis of the BA effect on depression remain unclear. The present study used the forced swimming test (FST) and changes in brain neurotransmitter levels to confirm the impact of BA on repeated restraint stress-induced behavioral and neurochemical changes in rats. Male rats received 10, 20, or 40 mg/kg BA (i.p.) 30 min prior to daily exposure to repeated restraint stress (2 h/day) for 14 days. Activation of the HPA axis in response to repeated restraint stress was confirmed by measuring serum corticosterone levels and the expression of corticotrophin-releasing factor in the hypothalamus. Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression. Thus, BA may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression.

• Tuberculosis and Respiratory Diseases
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• 제52권5호
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• pp.529-538
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• 2002

배 경 : 급성 천식발작 치료의 근간을 이루는 전신성 스테이로드는 골다공증, 쿠싱증후군, 당뇨, 고혈압, 출혈성 경향 등의 합병증으로 초기에 흡입용 스테로이드 사용이 추천되고 있다. 흡입성 스테로이드에는 정량분무식 에어로졸(MDI)나 분말형 흡입제(DPI), 무화에어로솔(nebulized aerosol)를 사용해오고 있는데 소아나 노인, 호흡곤란이 아주 심한 성인 환자에서는 무화 에어로졸(nebulized aerosol)을 이용한 budesonide흡입이 효과적일 수 있다. 이에 급성 발작으로 내원한 성인 천식 환자에 nebulized budesonide를 적용했을 때의 임상적인 효과와 스테로이드 보존 효과, 스테로이드의 부작용 중 하나인 시상하부-뇌하수체-부신 축의 이상에 대한 영향을 알고자 하였다. 방 법 : 1. 2000년 6월부터 2001년 9월까지 입원한 기관지 천식, 천식을 동반한 만성 폐질환 환자를 선택하여 1군은 전신성 스테로이드와 nebulized budesonide 2mg을 사용한 군, 2군은 전신성 스테로이드와 budesonide turbuhaler를 사용한 군, 3군은 단지 전신성 스테로이드만을 사용한 군으로 나누고서 최대호기유속, 대기중 동맥혈가스검사, 폐기능검사, 증상지수(호흡곤란, 기침, 야간천식, 천명음), 스테로이드 총량, 입원기간를 기록하여 분석하였다. 2. 내원 10일전부터 어떤 종류의 스테로이드도 쓰지 않았던 환자를 선택하여 budesonide turbuhaler와 nebulized budesonide를 사용한 군으로 나누어 24시간 소변내 코타솔 수치를 측정하여 비교하였다. 결 과 : 1. 임상효과: 순수한 천식환자에서 증상 지수(호흡곤란, 천명음, 기침, 야간천식), 스테로이드 용량, 재원일수, 폐기능 소견, 최대호기유속, 동맥혈가스검사에서 세군간의 차이가 없었고, 천식을 동반한 만성 폐쇄성 폐질환환자를 대상으로 비교했을 때도 세균간의 차이는 없었다. 2. 시상하부-뇌하수체-부진 축의 효과 : nebulizer budesonide 사용군은 turbuhaler 사용군과 마찬가지로 부신축의 억제효과가 있으나 두 군간에 차이는 없었다.(p=0.288) 결 론 : 성인 천식환자에서 급성 발작시 budesonide 형태에 관련없이 전신성 스테로이드만이 치료에 도움을 줄 수 있다는 사실을 확인하였고, 치료 용량의 nebulizer 사용군에서 turbuhaler 사용군과 마찬가지로 시상하부-뇌하수체-부신 축에 대한 억제작용이 있었다.

• 생물정신의학
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• 제11권1호
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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.