Bale Tracy L
Department of Animal Biology, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
Horm Behav. 2006 Nov;50(4):529-33. doi: 10.1016/j.yhbeh.2006.06.033. Epub 2006 Aug 8.
Depressive disorders are the most common form of mental illness in America, affecting females twice as often as males. The great variability of symptoms and responses to therapeutic treatment emphasize the complex underlying neurobiology of disease onset and progression. Evidence from human and animal studies reveals a vital link between individual stress sensitivity and the predisposition toward mood disorders. While the stress response is essential for maintenance of homeostasis and survival, chronic stress and maladaptive responses to stress insults can lead to depression or other affective disorders. A key factor in the mediation of stress responsivity is the neuropeptide corticotropin-releasing factor (CRF). Studies in animal models of heightened stress sensitivity have illustrated the involvement of CRF downstream neurotransmitter targets, including serotonin and norepinephrine, in the profound neurocircuitry failure that may underlie maladaptive coping strategies. Stress sensitivity may also be a risk factor in affective disorder development susceptibility. As females show an increased stress response and recovery time compared to males, they may be at an increased vulnerability for disease. Therefore, examination of sex differences in CRF and downstream targets may aid in the elucidation of the underlying causes of the increased disease presentation in females. While we continue to make progress in our understanding of mood disorder etiology, we still have miles to go before we sleep. As an encouraging number of new animal models of altered stress sensitivity and negative stress coping strategies have been developed, the future looks extremely promising for the possibility of a new generation of drug targets to be developed.
抑郁症是美国最常见的精神疾病形式，女性患者的发病率是男性的两倍。症状和对治疗反应的巨大变异性强调了疾病发生和发展背后复杂的神经生物学机制。来自人类和动物研究的证据揭示了个体应激敏感性与情绪障碍易感性之间的重要联系。虽然应激反应对于维持体内平衡和生存至关重要，但慢性应激和对应激刺激的适应不良反应会导致抑郁症或其他情感障碍。神经肽促肾上腺皮质激素释放因子（CRF）是调节应激反应性的一个关键因素。在应激敏感性增强的动物模型研究表明，CRF的下游神经递质靶点，包括血清素和去甲肾上腺素，参与了可能是适应不良应对策略基础的严重神经回路功能障碍。应激敏感性也可能是情感障碍易感性发展的一个危险因素。由于与男性相比，女性表现出更强的应激反应和更长的恢复时间，她们可能更容易患病。因此，研究CRF及其下游靶点的性别差异可能有助于阐明女性疾病发病率增加的潜在原因。虽然我们在理解情绪障碍病因方面不断取得进展，但在大功告成之前仍有很长的路要走。随着越来越多应激敏感性改变和消极应激应对策略的新动物模型被开发出来，开发新一代药物靶点的前景看起来非常乐观。
