• Korean Journal of Biological Psychiatry
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• v.18 no.4
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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.

• Women's Health Nursing
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• v.21 no.2
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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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• v.2 no.1
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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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• v.13 no.1
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• pp.3-14
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• 2002

Childhood psychic trauma appears to be a crucial factor in the development of serious disorders both in childhood and in adulthood. Traumatized children show strong tendency to revisualize or re-feel a traumatic events. Play and behavioral reenactments are frequent manifestations of both the single blow and the long-standing traumas in childhood. Those children who suffer the results of single, intense terror appear to exhibit detailed memory, retrospective reworkings and misperceptions. In long-standing or repetitive trauma, children would show psychic numbing, self-hypnosis, dissociation and rage. Child's brain is undergoing critical and sensitive periods of differentiation. During this time, developing central nervous system is exquisitely sensitive to stress. Stressor-activated neurotransmitters and hormones can play major roles in neurogenesis, migration, synaptogenesis, and neurochemical differentiation. Internal opiate system operates in some trauma and causes the victim to fail to respond, to avoid, to shut off feelings. Evidence is also accumulating in traumatology that dysfuntion of locus coeruleus and ventral tegmental neucleus system leads to catecholamine receptors hypersensitivity. This change result in hypervigilance, increased startle, affective lability, and increased autonomic nervous system hyperreactivity. Another site of action of trauma on the brain is hypothalamic-pituitary-adrenal axis. Individuals with PTSD do not have enough cortisol to halt the alarm reaction. When children are exposed to long-standing extreme events, massive attempts to protect the psyche and to preserve the self are put into gear. These developmental traumas mobilize various kinds of defense mechanisms. Massive denial, dissociation, self anesthesia, identification with aggressor and aggression turned against the self often lead to profound character changes in the youngsters.

• Clinical and Experimental Pediatrics
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• v.46 no.4
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• pp.400-403
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• 2003

Congenital adrenal hyperplasia(CAH) is a recognized cause of precocious pseudopuberty. Some children with CAH also develop true precocious puberty with early maturation of the hypothalamic-pituitary-gonadal axis. We review a case of CAH who eventually developed central precocious puberty nine months after initial treatment with corticosteroid. A 3-year-old boy visited complaining of rapid growth, a large penis and frequent penile erections. This patient was diagnosed with CAH with elevated 17-OH progesterone and cortical hypertrophy of adrenal gland on CT scan. His gonadotropin levels were within the normal prepubertal range. Even on treatment with corticosteroid he grew rapidly and had testicular enlargement, pubic hair development and rapid bone maturation. At second admission, his gonadotropin levels were elevated both basally and in response to LHRH stimulation, suggesting that the CAH led to early activation of pubertal gonadotropin secretion(true precocious puberty). He was treated with monthly depot injections of a LHRH analog in addition to the hydrocortisone. His second sexual characteristics regressed gradually and rate of linear growth and bone maturation decreased.

• Korean Journal of Veterinary Research
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• v.44 no.2
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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.

• Development and Reproduction
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• v.15 no.3
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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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• v.17 no.5
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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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• v.52 no.5
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• pp.529-538
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• 2002

Background : Many clinicians are reluctant to prescribe systemic corticosteroids to manage an asthmatic attack because of many complications such as osteoporosis, cushing's syndrome, diabetes, hypertension and bleeding tendency. The use of nebulized budesonide may be of value in some infants, old men, and in particular adult asthmatic patients who complain of severe dyspnea. A clinical validation and steroid-sparing effect of nebulized budesonide in asthmatic adults and COPD were evaluated, and the short-term effects of budesonide use on the HPA axis were assessed. Materials and Methods : Study A was prospectively done with 41 patients diagnosed with pure asthma and 30 patients diagnosed with COPD (including asthmatic component) in Soonchunhyang Hospital, Chunan from June. 2000 to Sep. 2001. They were treated with nebulized budesonide including systemic steroids (Group 1), a budesonide tubuhaler including a systemic steroid (Group 2), or only the systemic steroid(Group 3). The peak flow rate, arterial blood gas in room air, pulmonary function test, symptom scoring, steroid amount and hospital stay were analyzed. Study B was conducted with 19 patients to evaluate the short-term effects on the HPA axis of treatment with nebulized budesonide 1mg twice daily and a budesonide turbuhaler 5 puffs twice daily. The adrenal function was assessed prior to budesonide inhalation and after 7 days of budesonide inhalation. Results : In the pure asthmatic patients, the mean value of the symptoms (dyspnea, wheezing, cough, night asthma) or the arterial BGAs, total amounts of steroid or hospital stay and the difference in the results of the pulmonary function tests or peak expiratory flow rate were similar in the three groups. In COPD with an asthmatic component, there were no significant differences among the three groups. Although nebulized budesonide suppressed HPA function,(p=0.006) the HPA responses from the nebulized budesonide and turbuhaler budesonide were similar (p=0.288) Conclusion : This result suggests that systemic steroid should only be made available for acute asthmatic patients irrespective of the inhaled budesonides. Nebulized budesonide at the therapeutic dose has similar effects on the HPA axis compared to that of turbuhaler budesonide.

• 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.