憂鬱症生理病因之“神經可塑性”假說

Neuroplasticity Hypothesis in the Pathophysiology of Depression

蘇宗偉(Tsung-Wei Su) ； 李明濱(Ming-Been Lee)

《北市醫學雜誌》 2卷2期 (2005/02) Pp. 121-131

https://doi.org/10.6200/TCMJ.2005.2.2.01

摘要

憂鬱症患者之腦部影像學研究發現在海馬迴、前額葉、杏仁體有結構與功能的改變，這些改變被認為與憂鬱症神經可塑性病生理有關。憂鬱症的神經可塑性(neuroplasticity)，包括神經元新生(neurogenesis)與錐狀細胞樹突的修正(dendrites remodeling of pyramidal cell)等。本文回顧近年來的相關動物實驗與臨床研究文獻，探討影響神經可塑性的機制，如心理壓力、腎上腺皮質酮、神經滋養因子、麩氨酸興奮毒性(glutamate excitotoxicity)的影響，瞭解其在憂鬱症病生理學上的相關性。新型抗憂鬱劑如NMDA(N-methyl-D-aspartate)受體拮抗劑、瞭解其在憂鬱症病生理學上的相關性。新型抗憂鬱劑如NMDA(N-methyl-D-aspartate)受體活化劑則可增加海馬迴的神經元新生。以神經可塑性假說的觀點來審視情緒健康、抗壓性、與憂鬱的病理學，可以呈現目前所瞭解的憂鬱症發展，而單胺假說無法說明抗憂鬱劑療效不能立即出現的原因，神經可塑性假說則能提供較合理的解釋。

關鍵字

憂鬱症 ； 海馬迴 ； 神經可塑性 ； 神經元 ； 抗憂鬱劑

並列摘要

According to brain imaging studies, major depressive illness involves structural and functional changes in the hippocampus, prefrontal cortex, and amygdale. Neuroplasticity in depression refers to hippocampal neurogenesis and dendritic remodeling of pyramidal cells. This article reviews recent animal studies and clinical reports concerning neuroplasticity in depression. Depressive neuroplasticity may interact with mechanisms of psychosocial stress, cortisol, brain- derived neurotrophic factor, and glutamate excitotoxicity, all of which can contribute to depressive pathophysiology. NMDA (N-methyl-D-aspartate) receptor antagonists and AMPA (a-amino-3-hydroxy-5- methylisoxazole-4-propionic acid) receptor potentiators may have antidepressant properties and also increase hippocampal neurogenesis. If the role of neuroplasticity in emotional health, resistance to stress, and the pathophysiology of depression is found to be even partially accurate, it would represent a major development in our understanding of depression. The unanswered questions regarding the latency of action of antidepressants could be explained by the neuroplasticity hypothesis.

並列關鍵字

depressive disorder ； hippocampus ； neuroplasticity ； neuron ； antidepressant