신경염증과 정신질환
Neuroinflammation and Psychiatric Illness
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초록
생명체는 살아 있는 한 내외부의 자극에 대하여 저항하거나 적응한다. 이러한 과정을 ‘allostasis’라고 부르는데, 이 부하(allostatic load)가 감당할 수 있는 범위를 넘어서는 경우에는 기존의 평정 상태인 ‘default mode’가 조정되며, 일단변경된 default mode는 이후 자극이 소실되더라도 원상 복귀되지 않는 경향을 보인다.1) 최근 급속히 발달하고 있는 정신신경면역학의 관점에 따르면 allostasis에서 가장 중요한 비중을 차지하는 것이 바로 염증(inflammation)으로서 염증반응의 정도와 부위, 기간에 따라 다양한 결과들이 초래된다. 특히 만성적인 염증으로 인해 항상성이 유지되지 못하고 default mode가 변경되는 것이 질병과 노화의 기저에 깔린 주된 원인으로 지목되고 있다.2) 염증이란 조직의 손상에 대한 일종의 면역 반응으로 정의할 수 있는데, 과거에는 육안적 소견이나 백혈구 수치의 변화등으로밖에 판단할 수 없었으나 최근에는 cytokine이나 Creactive protein(이하 CRP)과 같이 염증 시 세포에서 분비되는 물질들을 표지자로 활용하게 되면서 미세염증의 측정이가능해졌다. 이에 따라 기분장애, 불안장애, 조현병, 신경발달장애, 신경퇴행성장애 등 각종 정신 질환들에 대해 기저에깔린 염증성 변화를 측정하는 연구들이 활발히 진행되고 있으며, 내과적 질환과 정신과적 질환 사이의 연결 고리도 염증과 관련하여 해석되고 있는 중이다. 원래 이러한 움직임은 C 형 간염이나 암으로 interferon 치료를 받는 사람의 90% 가까이에서 발생하는 피로감, 우울, 둔마 등의 sickness behavior에대한 관심에서 비롯되어3) 초기에는 전신적인 염증이 중추신경계에 미치는 영향에 대해 주로 조사되었으나 현재는중추신경계 내부에서 자체적으로 벌어지는 신경염증(neuroinflammation) 에 대해서도 연구의 초점이 맞추어지고 있다. 이 논문에서는 기존의 신경염증 연구들에서 주로 다루어지고 있는 소재들과 이를 바탕으로 제안된 메커니즘, 그리고 향후의 방향에 대해 개괄적으로 정리해 보고자 한다.
Abstract
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.
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