Gold P W, Chrousos G P
National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1284, USA.
Proc Assoc Am Physicians. 1999 Jan-Feb;111(1):22-34. doi: 10.1046/j.1525-1381.1999.09423.x.
The cardinal clinical manifestations of major depression with melancholic features include sustained anxiety and dread for the future as well as evidence of physiological hyperarousal (e.g., sustained hyperactivity of the two principal effectors of the stress response, the corticotropin-releasing-hormone, or CRH, system, and the locus ceruleus-norepinephrine, or LC-NE, system). Sustained stress system activation in melancholic depression is thought to confer both behavioral arousal as well as the hypercortisolism, sympathetic nervous system activation, and inhibition of programs for growth and reproduction that consistently occur in this disorder. Data also suggest that activation of the CRH and LC systems in melancholia are involved in the long-term medical consequences of depression such as premature coronary artery disease and osteoporosis, the two-three-fold preponderance of females in the incidence of major depression, and the mechanism of action of antidepressant drugs. In addition, recent data reveal important bidirectional interactions between stress-system hormonal factors in depression and neural substrates implicated in many discrete behavioral alterations in depression (e.g., the medial prefrontal cortex, important in shifting affect based on internal and external cues, the mesolimbic dopaminergic reward system, and the amygdala fear system). We have also advanced data indicating that the hypersomnia, hyperphagia, lethargy, fatigue, and relative apathy of the syndrome of atypical depression are associated with concomitant hypofunctioning of the CRH and LC-NE systems. These data indicate the need for an entirely different therapeutic strategy than that used in melancholia for the treatment of atypical depression, and they suggest that this subtype of major depression will be associated with its own unique repertoire of long-term medical consequences.
伴有抑郁特征的重度抑郁症的主要临床表现包括对未来持续的焦虑和恐惧，以及生理上过度觉醒的证据（例如，应激反应的两个主要效应系统——促肾上腺皮质激素释放激素（CRH）系统和蓝斑-去甲肾上腺素（LC-NE）系统持续活跃）。抑郁性抑郁症中应激系统的持续激活被认为会导致行为觉醒以及高皮质醇血症、交感神经系统激活，以及该疾病中持续出现的生长和生殖程序抑制。数据还表明，抑郁症中CRH和LC系统的激活与抑郁症的长期医学后果有关，如过早的冠状动脉疾病和骨质疏松症、女性在重度抑郁症发病率中高出两到三倍，以及抗抑郁药物的作用机制。此外，最近的数据揭示了抑郁症中应激系统激素因素与涉及抑郁症许多离散行为改变的神经基质之间重要的双向相互作用（例如，内侧前额叶皮质在根据内部和外部线索改变情绪方面很重要，中脑边缘多巴胺能奖赏系统和杏仁核恐惧系统）。我们也有数据表明，非典型抑郁症综合征的嗜睡、贪食、无精打采、疲劳和相对冷漠与CRH和LC-NE系统的功能减退有关。这些数据表明，治疗非典型抑郁症需要一种与治疗抑郁性抑郁症完全不同的治疗策略，并且表明这种重度抑郁症亚型将与其自身独特的长期医学后果相关。
