염증질환으로서의 우울증

송후림,우영섭,박원명 대한정신약물학회 2013 대한정신약물학회지 Vol.24 No.1

Inflammation is an immune response engaged with the reciprocal interactions among the neural, endocrine and immune system. From this psychoneuroimmunological view, inflammation is one of important allostatic loads contributory to depression. Sickness behaviors in the inflammatory state share many parts of depressive symptoms and patients treated with cytokines for various illnesses are at increased risk of developing depression. The dysfunctions of cytokines and hypothalamic-pituitary-adrenal axis have been widely investigated to find out inflammatory responses. Inflammatory mediators such as cytokines, glucocorticoid and C-reactive protein affect the etiopathogenesis of depression via altered monoamine and glutamate neurotransmission, glucocorticoid receptor resistance and neurogenesis. Although inflammation is subtle and not easy to be detected in the wide population, it is basal pathophysiology and plays an important role at least to the vulnerable patients. From this perspectives, inflammatory markers may be useful in the diagnosis and prediction of treatment response, leading to the possibility of tailored treatments. Understanding depression as a kind of inflammatory disease would provide new opportunities for the psychiatry beyond monoamine theory. 염증이란 내외부의 자극으로 인하여 조직이 손상됨으로써 유발되는 일종의 면역반응이다. 정신신경면역학의 관점에서 인체의 면역계과 내분비계, 신경계는 밀접하게 상호작용하고 있으며 염증은 allostatic load로 작용하여 이들을 변형시키는데, 이러한 결과 중 하나로 우울증이 발생할 수 있다. 염증 상태에서 보이는 sickness behavior은 우울증의 증상들과 유사성이 많으며, 다양한 질환의 치료로서 사이토카인을 사용하면 우울증의 발생율이 높아진다는 결과들은 염증과 우울증 사이의 관련성을 부각시켰다. 이와 관련하여 사이토카인, HPA축의 변화에 대한 연구들이 주로 수행되어 왔으며 염증표지자로서 IL-1, IL-2, IL-6, IFN-γ, TNF-α과 같은 사이토카인, CRF, 글루코코르티코이드와 같은 호르몬, CRP 등이 제시되었다. 염증반응은 신경전달물질의 합성과 전달, 글루코코르티코이드 저항성, 신경세포재생 등에 영향을 미쳐 우울증의 발생에 기여하고 회복을 저해하는 것으로 보인다. 아직까지 확정적인 염증표지자들은 없는 상태이지만, 최소한 취약성을 가진 환자에게는 중요하게 이용될 수 있을 것이다. 염증 매커니즘의 연구는 모노아민 이론의 한계를 보완하고 새로운 우울증 진단와 치료에 기여할 것으로 전망한다.

Apathy : 개념의 변화와 전망

송후림,박원명 대한신경정신의학회 2011 신경정신의학 Vol.50 No.5

Apathy is a common problem observed in many neuropsychiatric disorders. In the past, apathy was a conventional term that designated an absence of feeling and a flattening of affective responses. But recent research has produced the concept that the core feature of apathy is a lack of motivation and manifests as diminished goal-directed behavior, cognition, and emotion, including initiation and responsiveness deficiency. Now, apathy tends to be considered as a distinct clinical symptom and syndrome, but it is still conceptually ill-defined and there is no definite consensus on diagnostic criteria. Several rating scales such as the Apathy Evaluation Scale (AES) and Apathy Scale (AS) have been developed that assist in making a diagnosis of apathy and a measurment of severity. Neuroimaging studies have indicated that apathy is primarily a dysfunction of the frontal-subcortical system, which is called the motivational circuit, and can be divided into auto-activation, cognitive, emotional subtypes by various frontal-subcortical circuits which have been damaged. Dopamine (DA) and acetylcholine (Ach) have important roles in this area. Many studies have focused on the relationship between apathy and depression. The core feature of apathy is distinguished from depression, but they share too many incidental aspects to be divided off completely. It is because the diagnostic criteria of depression had developed before the new concept of apathy was proposed, so symptoms of apathy were included in the diagnostic criteria of depression. There is a need for consensus of definition and diagnostic criteria of apathy to facilitate future research, which may be able to get at the root of other neuropsychiatric disorders such as depression.

한국형 우울장애 약물치료 알고리듬 2012(I) : 정신병적 양상이 없는 주요우울장애

송후림,서정석,이황빈,박영민,홍정완,김원,왕희령,임은성,정종현,전덕인,홍진표,민경준,박원명 대한우울조울병학회 2013 우울조울병 Vol.11 No.1

Objectives : Nowadays, the pharmacological method is widely used as the standard treatment for depression. However, as a result of newer agents being introduced, pharmacological treatment strategy continues to develop. To overcome problematic nature in this trend, Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD)had been developed in 2002 and revised in 2006. And we propose the third revision of KMAP-DD reflecting the new research results and the latest trends in the areas of pharmacological treatment. Methods : 123 psychiatrists who had rich clinical experiences in depression were primary selected then surveyed via mail ;67 surveys were retrieved. This survey was constructed with 44 questions which contained overall treatment strategies to specific treatment strategies. Each treatment strategy or treatment option was evaluated with the overall score of nine and the following 95% confidence interval. Results were divided into three phases of recommendation; primary, secondary, tertiary. Results : The initial strategy for pharmacological treatment in major depression disorder without psychotic features is a single treatment of antidepressant which does not take into consideration of the severity of depressive episode. Also, primary recommendations for the mild to moderate episodes are SSRIs except fluvoxamine, SNRIs and mirtazapine. As for the severe episodes, SSRIs except fluvoxamine and flouxetine, SNRIs except milnacipran, and mirtazapine are recommended. In case of no response to the initial treatment, switching to another antidepres-sants or adding another antidepressants are the preferred methods. In case of partial responses to initial treatment, adding another antidepressants or combination of atypical antipsychotics are preferred. As for atypical antipsychot-ics, aripiprazole and quetiapine are selected primarily in the combined pharmacological therapy. Conclusion : If psychotic features are not apparent in major depression disorder, SSRIs, SNRIs and mirtazapine are initially consid-ered for single treatments. There are trends in which if enough response is not obtained in the initial treatment, stra-tegically adding another antidepressants are still preferred as well as combination of atypical antipsychotics. (J of Kor Soc for Dep and Bip Disorders 2013;11:5-11)

FMVSS 201U 법규 만족을 위한 B필라부 레이아웃 검토 연구

고형진(Hyongjin Ko),곽윤근(Yungeun Gwak),이영재(Youngjae Lee),김민찬(Minchan Kim),양수연(Sooyeon Yang),이병우(Byoungwoo Lee),서동조(Dongjo Seo),이승환(Seunghwan Lee) 한국자동차공학회 2020 한국자동차공학회 학술대회 및 전시회 Vol.2020 No.11

소아청소년 우울증 약물학적 치료지침 : 항우울제 치료와 자살 위험성

송후림,전태연,이영화,양수진,이지영,장정원,정소나,정현숙,조선진,임현우,이소영 대한우울조울병학회 2014 우울조울병 Vol.12 No.3

Objectives : The purpose of this guideline was to suggest recommendations for appropriate use of antidepressants in the child-adolescent depression. The relationship between antidepressant use and suicide was evaluated. Method : Four kinds of guidelines for the treatments of child-adolescent depression had been selected, and evidences and recommendations were extracted. This guideline was made through former and strict process of guideline adaptation in the Manual for Guideline Adaptation version 2.0 by National Evidence-based Healthcare Collaborating Agency. Results : Antidepressants were related with increase of suicidal behaviors in child-adolescent, but the causation was inconclusive. The combination treatment with cognitive behavior therapy could reduce suicidal behaviors. In case of prescribing antidepressants to child-adolescent, careful monitoring for the suicidal behaviors is required, and the combination treatments with cognitive behavior therapy are recommended. Conclusion : This guideline which provides optimal recommendations based on evidences, would contribute toward improving the quality of child-adolescent depression treatment.

중추신경계 외부의 세로토닌

송후림,우영섭,박원명 대한정신약물학회 2012 대한정신약물학회지 Vol.23 No.2

Most serotonin is found outside the central nervous system and functions much more than a neurotransmitter. Peripheral serotonin is produced by enterochromaffin cells in the gastrointestinal tract and secreted into blood. Serotonin, as a circulating amine, takes part in numerous biological processes including cardiovascular function, bowel motility, glucose metabolism and skeletal change. Serotonin signaling is regulated by serotonin receptors and serotonin transporters in multiple body organs. The drugs that manipulate the serotonergic system have been developed and used for the treatment of many systematic disease. The richness of serotonergic modulation in the whole body provide both a pharmacologic opportunity and challenge. 인체에서 대부분의 세로토닌은 중추신경계 밖에 존재하고 있으며, 단순히 신경전달물질로서의 기능뿐 아니라 거의 모든 기관에 걸쳐 다양한 역할을 수행하는 전방위적인 물질이다. 말초에서 세로토닌은 장내크롬친화성세포에서 생성된 다음 혈중으로 분비되어 전신을 순환한다. 세로토닌은 심혈관계, 소화기계, 내분비계, 골격계 등에 전신적으로 분포하는 세로토닌 수용체와 운반체를 통해 작용한다. 이러한 세로토닌 체계의 이상은 다양한 신체 질환의 원인이 되고 있으며, 세로토닌에 작용하는 약물들이 치료제로서 활용되고 있다. 신경정신계통의 약물을 사용할 때도 세로토닌의 변화로 인해 나타나는 전신적인 효과에 항상 주의를 기울여야 한다. 인체와 질병의 병태생리에서 세로토닌의 역할을 지속적으로 규명하는 것은 향후 질병의 치료와 약물의 개발에 많은 기회를 제공할 것이다.

소아청소년 우울증 약물학적 치료지침: 항우울제의 효과와 선택

송후림,정현숙,조선진,임현우,이소영,전태연,이영화,양수진,이지영,장정원,정소나 대한정신약물학회 2014 대한정신약물학회지 Vol.25 No.4

ObjectivezzThe purpose of this guideline was to suggest recommendations for appropriate use of antidepressants in the child-adolescent depression. The differences of efficacy among antidepressants were evaluated. MethodszzFour kinds of reliable guidelines for the treatments of child-adolescent depression had been selected, and evidences and recommendations were extracted by the executive committee under the peer review. All the process was applied to the Manual for Guideline Adaptation version 2.0 by National Evidence-based Healthcare Collaborating Agency. ResultszzSelective serotonin reuptake inhibitor (SSRI) could be considered for the treatments of moderate to severe child-adolescent depression. Among SSRIs, fluoxetine, sertraline, and escitalopram were recommended as having antidepressant efficacy compared with placebo, while paroxetine, venlafaxine, and tricyclic antidepressant were not recommended owing to lack of evidence. Another recommendation was to use combined treatment with cognitive behavioral therapy. ConclusionzzThis guideline, which was made through former and strict process of guideline adaptation, would contribute toward improving the quality of child-adolescent depression treatment by providing useful recommendations for the choice of antidepressant. 보건복지부지정 우울증임상연구센터의 소아청소년 우울증 약물학적 치료지침은 소아청소년 우울증 약물치료에 대한 적절한 권고안을 제공하기 위해 제작되었으며, 이 논문에서는 항우울제의 효과와 선택에 대해 다루었다. 소아청소년 우울증에 대한 항우울제 효과 연구들은 그 절대수가 적은데다 일관된 결과가 도출되는 경우가 많지 않아 확정적인 결론을 내리기가 어렵다. 이는 소아청소년 우울증 환자가 위약에 잘 반응하고 연령과 우울증의 중증도, 그리고 항우울제의 종류에 따라 약물 효과가 서로 다르게 나타나고 있기 때문으로 보인다. 현재까지의 소아청소년 우울증 진료지침들에서는 중등도 이상의 (소아)청소년 우울증 환자에게 일차적으로 fluox-etine을, 이차적으로 sertraline과 citalopram의 사용을 권고하고 있으며, 이외의 약물에 대해서는 유보적인 입장을 보이고 있다. 이러한 기존의 근거와 지침들을 바탕으로 본 지침에서는 중등도 이상의 (소아)청소년 우울증 환자에서 SSRI 계열 항우울제, 그 중에서도 fluoxetine, sertraline, escitalopram을 우선적으로 사용하고, 가급적 인지행동치료와 같은 심리치료를 병행할 것을 권고하였다. 그러나 소아에 대한 의약품 적정사용정보집 및 기존의 긍정적인 연구 결과들, 그리고 여러 전문가들의 의견을 고려할 때 다른 항우울제들도 전문가의 판단에 의해 필요하다고 여겨지는 경우라면 환자와 보호자에게 충분한 설명과 동의를 거쳐 신중하게 사용할 수도 있다고 본다. 물론 유효성과 안전성이 비교적 미확립된 paroxetine, venlafaxine, TCA의 사용에는 보다 각별한 주의를 기울여야 할 것이다. 현재까지 대부분의 국내 진료지침들은 비공식적인 합의를 통해 권고를 도출하고 있으며, 개발그룹 구성이나 개발 방법에 대한 자세한 기술이 누락되는 등 엄격한 방법론을 따르지 않았다는 단점이 있었다. 이 소아청소년 우울증 약물치료지침은 한국보건의료연구원이 제시한 공식적인 수용개작 절차를 빠짐없이 거쳐 제작된 것으로서, 향후 국내 임상 진료에 많은 도움이 될 수 있기를 기대한다.

자살의 신경생물학적 요인

송후림,우영섭,전태연 대한우울조울병학회 2012 우울조울병 Vol.10 No.1

Suicide is a complex behavior associated with various neurobiological and psychosocial factors. It is considered that genetic polymorphism combined with environmental stress such as child-adolescent trauma make differences in neurobiological systems, which cause psychiatric disorders or pessimistic personality, impulse-aggressive behaviors, lack of judgment, and finally result in suicidal behavior. Much progress in the neurobiology of suicide has been made over the several decades. There seems to be a hereditary disposition to suicide independent of psychiatric disorder. The changes in neurotransmitters, neurohormones, neurotrophic factors, cytokines, lipid metabolisms related with their genetic polymorphism can contribute to disturbance of signal transductions and neuronal circuits vulnerable to suicide. It is likely that the main factors are dysfunctions of serotonin (5-HT) and hypothalamus-pituitary-adrenal (HPA) axis. Our understanding about the neurobiology of suicide is still limited. However, clinical practice could be assisted by neurobiological findings capable of making the detection of risk populations with higher sensitivity and the development of new treatment interventions. The settlement of biological markers in suicidal behaviors and their relationships is required.

한국형 양극성 장애 약물치료 알고리듬 2018 : 신체 질환이 동반되었을 경우

송후림,박원명,윤보현,전덕인,서정석,김원,이정구,우영섭,정종현,김문두,손인기,심세훈,민경준 대한우울조울병학회 2018 우울조울병 Vol.16 No.3

Objectives : The fourth revision of Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was performed in 2018, to provide newer guidelines for clinicians. In this section, we examined expert opinions to facilitate clinical decisions relative to treating bipolar disorder with medical comorbidity. Methods : The survey was completed by the review committee, consisting of 61 experienced psychiatrists. This part of the survey constitutes treatment strategies, under major medical comorbidities. The executive committee analyzed results, and discussed the final production of algorithm. Results : Aripiprazole was the first-line medication for bipolar patients with metabolic syndrome, cardiovascular, hepatic, renal, and cerebrovascular comorbidities. Ziprasidone also was recommended as the first-line medication in case of metabolic syndrome. Lithium also was regarded as the first-line medication, in case of hepatic problems. Valproate also was considered as the first-line medication, in case of cerebrovascular problems. Conclusion : This study provided the most recent consensus among experts, for treatment of bipolar disorder with physical problems.

신경염증과 정신질환

송후림,이화영,심세훈,권영준,Song, Hoo Rim,Lee, Hwa-Young,Shim, Se-Hoon,Kwon, Young-Joon 대한생물정신의학회 2016 생물정신의학 Vol.23 No.1

Neuroinflammation is one of important allostatic loads contributory to the various psychiatric illness. It is mediated mainly by glial cells, which produce both proinflammatory and antiinflammatory cytokines, and the balance of them determines the inflammatory process in the central nervous system. S100 calcium-binding protein B, which is used as an inflammatory marker is also released by glial cells. In the molecular level, oxidative stress contributes to the neuroinflammation. Their disturbances have been revealed in the psychiatric illness and related with the dysregulation of the glutamatergic and monoaminergic systems. There is a possibility to use them as disease markers. The approach for inflammation using antiinflammatory drugs and antioxidants could be connected to the development of disease-modifying treatments. Also, a searching examination about specific subtypes who are vulnerable to inflammation in the patients is required to confirm their efficacy clearly.