Manji H K, Duman R S
Laboratory of Molecular Pathophysiology, NIMH, Building 49, Room B1EE16, 49 Convent Dr MSC 4405, Bethesda, MD 20892-4405, USA.
Psychopharmacol Bull. 2001 Spring;35(2):5-49.
Mood disorders have traditionally been conceptualized as neurochemical disorders, but there is now evidence from a variety of sources demonstrating regional reductions in central nervous system (CNS) volume, as well as reductions in the numbers and/or sizes of glia and neurons in discrete brain areas. Although the precise cellular mechanisms underlying these morphometric changes remain to be fully elucidated, the data suggests that mood disorders are associated with impairments of structural plasticity and cellular resilience. Recent preclinical and clinical studies have shown that signaling pathways involved in regulating cell survival and cell death are long-term targets for the actions of antidepressants and mood stabilizers. Antidepressants, lithium, and valproate indirectly regulate a number of factors involved in cell survival pathways, including CREB, BDNF, Bcl-2, and MAP kinases, and may thus bring about some of their delayed long term beneficial effects via underappreciated neurotrophic effects. The future development of treatments that more directly target molecules involved in critical CNS cell survival and cell death pathways thus hold promise as novel, improved long-term treatments for mood disorders.
情绪障碍传统上被概念化为神经化学紊乱，但现在有来自各种来源的证据表明中枢神经系统（CNS）体积存在局部减少，以及离散脑区中神经胶质细胞和神经元的数量和/或大小减少。尽管这些形态测量变化背后的确切细胞机制仍有待充分阐明，但数据表明情绪障碍与结构可塑性和细胞弹性受损有关。最近的临床前和临床研究表明，参与调节细胞存活和细胞死亡的信号通路是抗抑郁药和心境稳定剂作用的长期靶点。抗抑郁药、锂盐和丙戊酸盐间接调节参与细胞存活通路的多种因素，包括CREB、BDNF、Bcl-2和MAP激酶，因此可能通过未被充分认识的神经营养作用产生一些延迟的长期有益效果。因此，更直接靶向参与关键CNS细胞存活和细胞死亡通路的分子的治疗方法的未来发展有望成为治疗情绪障碍的新型、改进的长期治疗方法。
