스트레스의 신경생물학적 이해

유범희,우종민,Yu, Bum-Hee,Woo, Jong-Min 한국정신신체의학회 2001 정신신체의학 Vol.9 No.1

스트레스는 여러 가지 정신질환의 병태생리와 관련되는 것으로 알려졌다. 최근 여러 가지 동물 모델이 제시되고 뇌에 대한 연구가 활발해지면서 스트레스의 선경생물학적 기전에 대해 많은 사실이 밝혀지고 있다. 저자들은 동물과 사람을 대상으로 스트레스가 지각되고 대뇌에서 처리되고 신경내분비적 반응으로 전환되는 경로를 밝히고자 했던 최근의 연구들을 고찰하였다. 과거 변연계-시상하부-뇌하수체-부신 축(LHPA axis)과 자율신경계가 스트레스반응의 신경생물학적 담당자로 가장 많이 연구되어 왔으나, 최근에는 노르에피네프린(NE), 세로토닌, GABA/Glutamate, 도파민, 아세틸콜린 등의 신경전달물질과 부신피질자극호르몬방출인자(CRF), arginine vasopressin. glucocorticoid 등의 신경호르몬이 상호작용을 하면서 스트레스반응에 관계되는 것으로 알려지고 있다. 이러한 대뇌의 신경전달체계는 LHPA축과 유기적으로 연관되면서 스트레스반응을 매개하며, 구조적으로도 LHPA축은 해마, 편도 등 다양한 대뇌 부위와 연결된다. LHPA축은 이렇게 중층적으로 조절되는데, 여기에 생기는 이상은 만성 스트레스나 우울증 등 병적 상태와 관련된다. CRF는 LHPA축의 호르몬 역할 이외에 대뇌의 광범위한 부위에 분포하면서 신경전달물질로서 기능하며 다양한 스트레스반응을 매개한다. 스트레스를 주변 자율신경계가 활성화되는데, 청색반점에서 기시하는 NE계가 직접 자극되어 카테콜아민을 분비하기도 하지만, CRF나 다른 신경전달계가 먼저 자극되면서 간접적으로 활성화되기도 한다. 특히 CRF와 NE계는 서로 자극시키는 feed-forward 상호작용을 하며, 이것이 생체가 외부환경의 도전에 맞서 내분비계 뿐만 아니라 중추신경계를 동원하는 데 중요한 역할을 할것으로 보인다. 또한 CRF-NE 상호작용은 불안이나 우울 등 비정상적 스트레스반응의 병태생리를 이해하는 데 중요한 역할을 할 것으로 시사된다. 스트레스반응은 구조적, 신경화학적, 유전적 수준의 다양한 신경생물학적 작용을 통해 일어나며, 이에 대한 연구는 스트레스반응의 병태생리를 밝히고 불안장애, 기분장애 등 정신질환의 원인 규명과 치료에도 크게 기여할 것으로 보인다. Stress has been linked to the pathophysiology and pathogenesis of various psychiatric illnesses. Over the past few years, our understanding of the brain and neuroendocrine systems that are linked to stress responses has increased enormously. This article reviews a series of animal and human studies to understand what are the central pathways by which stress is perceived, processed, and transduced into a neuroendocrine response. We focus on the limbic-hypothalamic-pituitary-adrenal(LHPA) axis and several neurotransmitter systems such as norepinephrine, CRF, serotonin, acetylcholine, and dopamine. LHPA stress circuit is a complex system with multiple control mechanisms which are altered in pathological states. CRF and related peptides in the central nervous system appear to enhance behavioral responses to stressors. Norepinephrine systems are also activated by stressors and cause the release of catecholamines from the autonomic nervous system. CRF-norepinephrine interaction makes a feed-forward system which may be important for an organism to mobilize not only the pituitary system but also the central nervous system, in response to environmental challenges. The interactions among several neurotransmitters and endocrine systems appear to play key roles in mediating various behavioral and psychological stress responses involving abnormal responses to stressors such as anxiety and affective disorders.

현재 불안 장애의 분류 : 타당한가?

유범희,이인수,Yu Bum-Hee,Lee In-Soo 대한불안의학회 2005 대한불안의학회지 Vol.1 No.1

The Diagnostic and Statistical Manual 4th edition (DSM-IV) has been widely accepted and used for international classification of mental disorder. The DSM has been changed to improve diagnostic reliability and validity through descriptive and categorical approaches which was undertaken atheoretically. The authors reviewed current studies about the DSM-IV classification system and the diagnostic issues of representative categories of anxiety disorder. The authors concluded that the anxiety disorder classification system in DSM-IV has limitations such as a lack of empirical consideration for overlapping features of anxiety disorders and a lack of discriminant validity. To improve diagnostic validity and revise the current DSM-IV classification system, the authors suggested 1) more longitudinal studies for collecting empirical evidence, 2) decreasing the dependence upon operational criteria, 3) deceasing diagnostic boundary blurring, 4) developing disease specific biological diagnostic techniques and 5) continued collaboration between the DSM and International Classification of Diseases (ICD) systems.

과민성 장증후군에서 베타-아드레날린 수용체 민감도와 기분상태, 결장감각과의 관계

유범희 ( Bum Hee Yu ),강은호 ( Eun Ho Kang ),김현서 ( Hyun Seo Kim ),이풍렬 ( Poong Lyul Rhee ) 대한소화기기능성질환·운동학회 2006 Journal of Neurogastroenterology and Motility (JNM Vol.12 No.1

목적: 과민성 장증후군의 원인으로 크게 감각기능 이상, 운동기능 이상, 스트레스를 비롯한 정신사회적 요인, 기분 혹은 정서적 문제와 자율신경계통의 이상 등이 거론된다. 본 연구에서는 우울증이나 불안장애를 앓고 있지 않은 과민성 장증후군 환자에서 베타-아드레날린 수용체 민감도와 기분 상태, 결장감각 간의 관계를 살펴보고자 하였다. 대상 및 방법: Rome-II 기준에 의해 진단 받은 과민성 장증후군 환자 18명과 정상 대조군 18명을 비교하였다. 베타-아드레날린 수용체 민감도 측정을 위해 아이소프로테레놀 (isoproterenol) 자극을 이용한 chronotropic 25 dose (CD(25))를 사용하였다. 결장감각기능 측정을 위해서는 풍선확장검사(balloon distention test)를 시행하였다. 기분 상태는 해밀톤 우울 척도와 해밀톤 불안 척도를 이용하여 측정하였다. 결과: 베타-아드레날린 수용체 민감도는 정상대조군에 비해 환자군에서 유의하게 높았고, 해밀톤 우울 척도와 해밀톤 불안 척도도 환자군에서 높게 나타났다. 환자군에서 베타- 아드레날린 수용체 민감도는 불안 정도에 비례하였고, 특히 변비-우세형 과민성 장증후군 환자들의 경우 결장의 불편감은 베타-아드레날린 수용체 민감도와 비례하는 것으로 나타났다. 결론: 우울증이나 불안장애가 동반되지 않은 과민성 장증후군에서 베타-아드레날린 수용체 민감도가 증가되어 있으며 변화된 베타-아드레날린 수용체 민감도와 불안감의 수준이 일부 과민성 장증후군 환자에서는 결장감각 이상과 관련될 수 있다는 것을 시사한다. Background/Aims: Autonomic abnormalities and mood state have been frequently reported in patients with irritable bowel syndrome (IBS). This study was designed to assess β-adrenergic receptor sensitivity and mood in IBS patients without depressive or anxiety disorders, and to examine the relationship among β-adrenergic receptor sensitivity, mood and colonic sensation in IBS patients. Methods: Eighteen IBS patients were compared with the same number of age- and sex- matched normal control subjects. To assess β-adrenergic receptor sensitivity, we measured the chronotropic 25 dose (CD25). The balloon distension test was performed to measure colonic sensation in the IBS patients. The Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A) were also used. Results: The β-adrenergic receptor sensitivity was significantly higher in the patient group than in the control group, and the IBS patients showed higher scores on the HAM-D and HAM-A. The β-adrenergic receptor sensitivity was positively correlated with HAM-A scores in all IBS patients and the perception of discomfort in the constipation-predominant IBS patients. Conclusions: These results suggest that β-adrenergic receptor sensitivity is increased in IBS patients who do not have depressive or anxiety disorders. Anxiety and altered β-adrenergic receptor sensitivity may be related to colonic sensation in some IBS patients. (Kor J Neurogastroenterol Motil 2006;12:63-68)

정신신체장애의 이해와 치료

유범희(Bum-Hee Yu) 대한스트레스학회 2004 스트레스硏究 Vol.12 No.1

정신신체장애의 이해와 치료

유범희(Bum-Hee Yu) 대한스트레스학회 2004 스트레스硏究 Vol.12 No.2

한국형 공황장애 약물치료 알고리듬 2008 : 공황장애의 진단, 치료 반응과 관해의 평가

김민숙,유범희,김찬형,윤세창,이상혁,서호석,양종철,한국형 공황장애 약물치료 알고리듬 2008 연구그룹,Kim, Min-Sook,Yu, Bum-Hee,Kim, Chan-Hyung,Yoon, Se-Chang,Lee, Sang-Hyuk,Suh, Ho-Suk,Yang, Jong-Chul 대한불안의학회 2008 대한불안의학회지 Vol.4 No.1

Objective : This article is a part of the Korean Medication Algorithm Project for Panic Disorder, which aims to build consensus regarding the diagnosis, treatment response and achievement of clinical remission for patients with panic disorder in Korea. Methods : The questionnaire used in this article had parts : 1) diagnosis, 2) treatment response, and 3) remission for patients with panic disorder. The questionnaire was completed by each of 54 Korean psychiatrists who had much experience in treating patients with panic disorder. We classified the experts' opinions into 3 categories (first-line, second-line, and third-line) using the ${\chi}^2$-test. Results : Five factors were considered in this research : panic attack, anticipatory anxiety, phobic avoidance, severity of illness, and psychosocial disability. Most reviewers agreed that the presence of a panic attack was the most important factor in the diagnosis of patients with panic disorder. Phobic avoidance was included in the first-line category, whereas the severity of illness and psychosocial disability were included in the second-line category. Most reviewers also agreed that the presence of a panic attack was the most important factor in determining the appropriate treatment response, and it was included in the first-line category along with several other items. To determine remission status, the patients' scores on tests pertaining to the severity of panic attack, anticipatory anxiety, phobic avoidance, severity of illness and psychosocial disability should be less than 3.0-3.3 on a 9-point Likert scale. Conclusion : We suggest useful information for making a diagnosisof panic disorder, determining the appropriate treatment response and identifying remission in panic disorder patients on the basis of the results of a nationwide survey of experts in Korea.

불안과 노어에피네프린

심현보,유범희,Sim, Hyun-Bo,Yu, Bum-Hee 대한불안의학회 2006 대한불안의학회지 Vol.2 No.1

Anxiety has been suggested to be related to many neurotransmitters in brain, such as norepinephrine, serotonin, dopamine, cholecystokinin, and gamma-amino butyric acid. There are many studies to examine the relationship between anxiety and norepinephrine, and norepinephrine seems to be clearly related to the development of anxiety. We suggest that future studies to explore the pathophysiology of anxiety should be necessary, which include studies on antianxiety drugs, genetic studies, animal model studies, and brain imaging studies.

기분과 성격특성이 정신생리적 반응에 미치는 영향

구문선,유범희,Koo, Moon-Sun,Yu, Bum-Hee 대한수면의학회 2001 수면·정신생리 Vol.8 No.1

목 적 : 본 연구는 정상인에서 바이오피드백 시스템으로 측정된 정신생리적 변인들과 기분 및 성격 특성에 미치는 영향을 알아보고자 하였다. 방 법 : 광고를 통해 모집한 내과적, 정신과적 질환의 병력이 없는 건강한 성인남녀 50명을 대상으로 스필버거 특성불안척도, 베크 우울척도, 성인용 아이젱크 성격검사를 측정하였다. 정신생리학적 변인은 J & J 바이오피드백 시스템을 이용하여 말초피부 온도, 피부전도 반응, 전완 근전도, 전두근 근전도의 수준을 기저기, 스트레스기, 회복기의 3시기로 나누어서 측정하였다. 또한 각 심리척도의 상위 10명, 하위 10명을 고집단(고불안, 고우울, 외향성, 고신경증)과 저집단(저불안, 저우울, 내향성, 저신경증)으로 분류하여 고/저 집단간의 정신생리적 반응의 차이를 t-test, repeated measures ANOVA, Pearson 상관분석을 통해 살펴보았다. 결 과 : 특성불안과 정신생리적 반응과의 관계를 살펴보았을 때, 전완 근전도의 스트레스 반응만이 특성불안과 유의한 상관관계를 나타냈을 뿐(r=0.282, p<0.05), 다른 정신생리적 반응과 연관성은 관찰되지 않았다. 우울감은 기저기와 회복기의 전완 근전도에서 각각 부적 상관관계를 나타냈다(r=-0.299, p<0.05;r=-0.314, p<0.05). 고우울 집단과 저우울 집단을 비교한 결과 전두근 근전도가 스트레스와 회복반응에서 유의한 상호작용 효과를 나타냈다 (F=4.26, p<.05). 외향적인 집단은 내향적인 집단에 비해 스트레스기에 측정된 전완 근전도가 높은 것으로 나타났다. 결 론:본 연구를 통해 정상인에게서 기분과 성격 특성은 바이오피드백 시스템으로 측정한 정신생리적 반응과 연관이 있음을 확인했다. 이는 각종 정신과적 장애에서 동반되는 정신생리적 변인의 이상소견을 해석하는데 있어 반드시 고려해야 할 점으로 생각된다. Objectives: This study examined the effect of mood and personality characteristics on psychophysiological responses measured by a biofeedback system in a normal population. Methods: Fifty healthy volunteers without any history of medical or psychiatric illnesses participated in this study. We measured the Spielberger trait anxiety inventory, Beck depression inventory, and Eysenck personality questionnaires in these subjects. Using the J & J biofeedback system, we also measured skin temperature, electrodermal response, forearm and frontal electromyography (EMG)s in 3 experimental conditions of baseline, stress, and recovery phases. Results: Trait anxiety did not show any significant correlation with psychophysiological responses except stress response in forearm EMG levels(r=0.282, p<0.05). Depressed mood was negatively correlated with forearm EMG levels in baseline (r=-0.299, p<0.05) and recovery phases(r=-0.314, p<0.05). Subjects with relatively high levels of depressed mood showed different stress and recovery responses in frontal EMG levels compared with those with relatively low levels of depressed mood (F=4.26, p<0.05). Extroverted subjects showed higher levels of forearm EMG than introverted ones in stress phase. Conclusion: Mood and personality characteristics in healthy subjects are closely related with psychophysiological responses measured by a biofeedback system. We suggest that mood and personality characteristics should be considered as important variables in analyzing abnormal psychophysiological responses in some psychiatric patients.

공황장애 치료에 대한 한국형 알고리듬 개발(1) - 배경, 조직구성, 알고리듬 개발의 원칙, 개발계획, 개발방법

이상혁,유범희,김찬형,윤세창,Lee, Sang-Hyuk,Yu, Bum-Hee,Kim, Chan-Hyung,Yoon, Se-Chang 대한불안의학회 2007 대한불안의학회지 Vol.3 No.2

In this special article, we presented the organization of the work group, basic principles of the algorithm, future plan and methods for developing a treatment algorithm for panic disorder in Korea. The psychiatrist work group from the Korean Association of Anxiety Disorders began to develop a treatment algorithm designed to improve the management of Korean patients with panic disorder by incorporating better evaluation techniques and treatment procedures. We have reviewed the treatment guidelines and algorithms for panic disorder published thus far, including the Practice Guideline for the Treatment of Patients with Panic Disorder established by the American Psychiatric Association, the Management of Anxiety (Panic Disorder, with or without Agoraphobia, and Generalized Anxiety Disorder) in Adults in Primary, Secondary and Community Care established by the National Institute for Clinical Excellence, and the Clinical Practice Guidelines established by the Canadian Psychiatric Association. We developed the basic materials to be used in the treatment algorithm for the management of panic disorder in Korea. Therefore, in this special article, we intro-duce the goal of the algorithm and the details of the algorithm development.

불면증의 생리학적 모델

심현보,유범희,Sim, Hyun-Bo,Yu, Bum-Hee 대한수면의학회 2009 수면·정신생리 Vol.16 No.1

Relatively little is known about the neurobiology of insomnia, despite its wide prevalence and broad medical impact. Although much is still to be learned about the pathophysiology of the disorder, identification, systematic assessment, and appropriate treatment are clearly beneficial to patients. Recent research, using quantitative EEG, polysomnography (PSG), multiple sleep latency test (MSLT) and neuroimaging techniques, suggests that some broad areas can be identified as possible pathophysiological models. Sleep-wake homeostat model hypothesizes a failure in homeostatic regulation of sleep, an attenuated increase in sleep drive with time awake, and/or defective sensing of sleep need. Circadian clock model hypothesizes a dysfunctional circadian clock, resulting in changes in the timing of sleep-wake propensity that are incompatible with normal sleep. Intrinsic sleep-wake state mechanism model suggests that abnormal function of insomnia comprises the systems responsible for expression of the sleep states themselves. Extrinsic over-ride mechanism (stress-response) model suggests that insomnia reflects the consequences of overactivity of one of the systems considered "extrinsic" to normal sleep-wake control. Many current therapies for insomnia are based on these physiological models. Several attempts have been made to create a physiological model that would explain this disorder and could be used as a foundation for treatment. However, it appeared that no model can fully explain and clarify all aspects of insomnia. Future research should be necessary to expand our knowledge on the biological dimensions of insomnia.