Corticotropin-releasing factor, vasopressin and receptor systems in depression and anxiety
Corticotropin-releasing factor, vasopressin and receptor systems in depression and anxiety
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DOI：
10.1007/s00726-006-0333-y
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发表时间：
2006-10-01
期刊：
影响因子：
3.5
通讯作者：
Keck, M. E.
中科院分区：
文献类型：
--
作者：
Keck, M. E.
情感障碍往往是慢性和危及生命的疾病：据估计，自杀是10-15%的重度抑郁症患者的死亡原因。重度抑郁症是最普遍和最昂贵的脑部疾病之一，全球高达20%的人口患有中度至重度形式的疾病。只有50%的抑郁症患者在目前可用的抗抑郁药物治疗中表现出完全缓解，这些药物治疗是基于20世纪50年代的偶然发现。以前被低估的其他严重抑郁症相关的有害健康影响越来越多地被认识到。流行病学研究提供了大量证据表明，抑郁症患者发生心血管疾病和心肌梗死后死亡的风险增加2-4倍。大多数患有情感障碍的患者在其应激激素调节中具有可测量的变化，这反映在中枢和外周应激激素分泌升高或对神经内分泌激发试验的激素反应改变。近年来，这些改变越来越多地被转化为解决疾病发病机制的可验证假设。精细的分子技术和基因工程小鼠的产生允许特异性靶向参与促肾上腺皮质激素释放因子（CRF）和加压素（AVP）系统元件调节的单个基因。累积的证据使一个强有力的情况下，涉及这些系统的功能障碍的病因和发病机制的抑郁症和病理性焦虑症。将这些进展转化为新的治疗策略已经开始。
Affective disorders tend to be chronic and life-threatening diseases: suicide is estimated to be the cause of death in 10-15% of individuals with major depressive disorders. Major depression is one of the most prevalent and costly brain diseases with up to 20% of the worldwide population suffering from moderate to severe forms of the disease. Only 50% of individuals with depression show full remission in response to currently available antidepressant drug therapies which are based on serendipitous discoveries made in the 1950s. Previously underestimated, other severe depression-associated deleterious health-related effects have increasingly been recognized. Epidemiological studies have provided substantial evidence that patients with depression have a 2-4-fold increased risk both of developing cardiovascular disease and of mortality after experiencing a myocardial infarction. The majority of patients suffering from affective disorders have measurable shifts in their stress hormone regulation as reflected by elevated secretion of central and peripheral stress hormones or by altered hormonal responses to neuroendocrine challenge tests. In recent years, these alterations have increasingly been translated into testable hypotheses addressing the pathogenesis of illness. Refined molecular technologies and the creation of genetically engineered mice have allowed to specifically target individual genes involved in regulation of corticotropin releasing factor (CRF) and vasopressin (AVP) system elements. The cumulative evidence makes a strong case implicating dysfunction of these systems in the etiology and pathogenesis of depression and pathological anxiety. Translation of these advances into novel therapeutic strategies has already been started.