Stress sensitivity and the development of affective disorders
Stress sensitivity and the development of affective disorders
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DOI：
10.1016/j.yhbeh.2006.06.033
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发表时间：
2006-11-01
影响因子：
3.5
通讯作者：
Bale, Tracy L.
中科院分区：
文献类型：
--
作者：
Bale, Tracy L.
抑郁症是美国最常见的精神疾病，女性的患病率是男性的两倍。症状和对治疗性治疗的反应的巨大变化强调了疾病发作和进展的复杂的潜在神经生物学。来自人类和动物研究的证据揭示了个体压力敏感性和情绪障碍倾向之间的重要联系。虽然应激反应对于维持体内平衡和生存是必不可少的，但慢性应激和对应激损伤的适应不良反应可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）是调节应激反应的一个关键因素。对应激敏感性增强的动物模型的研究表明，CRF下游神经递质靶点（包括5-羟色胺和去甲肾上腺素）参与了可能导致适应不良应对策略的严重神经回路故障。压力敏感性也可能是情感障碍发展易感性的一个危险因素。与男性相比，女性的应激反应和恢复时间更长，因此她们可能更容易患病。因此，检查CRF和下游靶点的性别差异可能有助于阐明女性疾病表现增加的根本原因。虽然我们在对情绪障碍病因的理解方面不断取得进展，但在我们睡觉之前，我们还有很长的路要走。随着压力敏感性改变和消极压力应对策略的新动物模型的开发，未来看起来非常有希望开发新一代药物靶点的可能性。(c)2006年爱思唯尔公司All rights reserved.
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. (c) 2006 Elsevier Inc. All rights reserved.