Stress-induced Changes in Central Nervous System: Implication for Psychiatric Disorders

林 博彥, Yu Chien Lee, 文 榮光

Research output: Contribution to journalJournal Article peer-review

Abstract

  壓力能改變成年哺乳動物腦部結構與功能。壓力反應受到下視丘---腦下垂體---腎上腺(HPA)軸回饋抑制之調控,其間腎上腺皮質作用在下視丘、腦下垂體、及海馬迴。海馬迴受損導致腎上腺皮質及皮質刺激素釋放激素(CRH)的過度分泌,這顯示出海馬迴在HPA軸回饋抑制扮演重要角色。高度壓力或腎上腺皮質都會都會傷害認知功能,特別是外顯記憶的部分,而外顯記憶主要是透過海馬迴來運作。腎上腺皮質透過三種細胞機制來改變海馬迴神經元結構或功能,包括抑制dentate gyrus的神經元增生,神經樹突萎縮,及改變突觸可塑性(包括LTP 及LTD)。創傷後壓力症候群及重鬱症有些共同的特徵,包括HPA 軸功能失調,異常之GR 功能及腎上腺皮質濃度,海馬迴萎縮,認知功能缺損。且心理社會壓力往往是主要誘發因子之一。創傷後壓力症候群的研究顯示出過度敏感之HPA 軸,腎上腺皮質濃度較低,增強的回饋抑制。相反地,憂鬱症研究顯示GR 功能受損,高度活化之HPA軸,腎上腺皮質濃度升高。因此,研究GR 功能的調節機轉可幫助我們深刻了解壓力如何塑造創傷後壓力症候群及重鬱症的病理過程,並改善這些疾病的藥物治療策略。
  Stress changes the morphology and functional state of adult mammalian brains. These stress responses are regulated by feedback inhibition of the hypothalamic- pituitary-adrenal (HPA) axis, through which corticosteroids act on the hypothalamus, pituitary gland, and hippocampus. The fact that hippocampal lesions are associated with hypersecretion of corticosteroids and increased production of corticotropin- releasing hormone (CRH) suggests the importance of the hippocampus in this feedback. Both stress and corticosteroids can decrease cognitive performance in both animal and human studies, and this is especially true for the type of knowledge known as "explicit" knowledge, which is processed mainly in the hippocampus. Corticosteroids modify the structure and function of hippocampal neurons through three cellular mechanisms: 1) inhibition of neurogenesis in dentate gyrus (DG); 2) atrophy of dendritic processes; and 3) synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). Post-traumatic stress disorder (PTSD) and major depression share characteristics including HPA axis dysregulation, abnormal GR function and cortisol levels, hippocampal atrophy, cognitive deficits, and psychosocial stress as one of the major precipitating factors. Studies of PTSD show evidence of a highly sensitized HPA axis characterized by decreased basal cortisol levels and enhanced negative feedback. In contrast, depression shows GR resistance characterized by hyperactivity of the HPA axis, increased cortisol levels, and decreased negative feedback. Further studies on the mechanisms of GR function regulation may be able to determine how stress shapes the pathogenesis of depression and PTSD and help refine pharmacotherapy of these illnesses.
Original languageAmerican English
Pages (from-to)87-104
Journal臺灣精神醫學
Volume16
Issue number2
StatePublished - 2002

Keywords

  • depression
  • glucocorticoid receptor
  • stress

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