Potter W Z, Manji H K
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Clin Chem. 1994 Feb;40(2):279-87.
Despite extensive research, the biochemical abnormalities underlying the predisposition to and the pathogenesis of affective disorders remain to be clearly established. Efforts to study norepinephrine (NE) output and function have utilized biochemical assays, neuroendocrine challenge strategies, and measures of peripheral blood cell receptors; the cumulative database points to a dysregulation of the noradrenergic system. Depressed patients (in particular, melancholic, unipolar subjects) excrete disproportionately greater amounts of NE and its major extraneuronal metabolite, normetanephrine, than do controls. Depressed patients also show subsensitive neuroendocrine (growth hormone) and biochemical (inhibition of adenylate cyclase) responses to alpha 2-adrenergic agonists, suggesting that subsensitivity of nerve terminal alpha 2 autoreceptors may underlie the exaggerated plasma NE observed in response to various challenges in affective disorders. Future advances in brain imaging techniques and in the molecular biology of adrenergic receptor-coupled signal transduction systems offer promise for meaningful advances in our understanding of the pathophysiology of affective disorders.
尽管进行了广泛的研究，但情感障碍易感性和发病机制背后的生化异常仍有待明确确定。研究去甲肾上腺素（NE）输出和功能的努力采用了生化检测、神经内分泌激发策略以及外周血细胞受体测量方法；累积的数据库表明去甲肾上腺素能系统存在失调。与对照组相比，抑郁症患者（尤其是抑郁性、单相抑郁症患者）排泄的NE及其主要的细胞外代谢产物去甲变肾上腺素的量不成比例地更高。抑郁症患者对α2肾上腺素能激动剂的神经内分泌（生长激素）和生化（腺苷酸环化酶抑制）反应也表现出反应迟钝，这表明神经末梢α2自受体的反应迟钝可能是情感障碍中对各种刺激所观察到的血浆NE过高的基础。脑成像技术以及肾上腺素能受体偶联信号转导系统分子生物学的未来进展有望为我们对情感障碍病理生理学的理解带来有意义的进展。
