Influences of dopaminergic system dysfunction on late-life depression.
Influences of dopaminergic system dysfunction on late-life depression.
复制标题
DOI：
10.1038/s41380-021-01265-0
复制
发表时间：
2022-01
影响因子：
11
通讯作者：
Rutherford BR
中科院分区：
文献类型：
--
作者：
Taylor WD;Zald DH;Felger JC;Christman S;Claassen DO;Horga G;Miller JM;Gifford K;Rogers B;Szymkowicz SM;Rutherford BR
认知、奖励加工和运动功能的缺陷是与衰老和抑郁症相关的临床特征。患有老年抑郁症的人通常表现出这些领域的损伤，所有这些都是由多巴胺能回路的功能调节的。由于多巴胺能功能随着正常衰老和炎症负担的增加而下降，多巴胺在晚年抑郁症中的作用可能特别突出。我们回顾了多巴胺在抑郁症发病机制中的作用，以及多巴胺功能如何随年龄变化和炎症的影响。应用研究领域标准（RDoC）倡议的观点，我们随后回顾了多巴胺能信号传导如何影响这些领域的工作，特别是关注认知、正价和感觉运动系统。我们提出了一个统一的模型，结合衰老和轻度炎症对多巴胺能功能的影响，并由此对认知、奖励处理和运动功能产生负面影响。这些系统之间的相互作用可能影响抑郁表型的发展，一个领域的初始缺陷会加强其他领域的衰退。该模型将RDoC概念扩展到晚年抑郁症，同时也为新颖和个性化的干预提供了机会。
Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflammatory burden, the role of dopamine may be particularly salient for late-life depression. We review the literature examining the role of dopamine in the pathogenesis of depression, as well as how dopamine function changes with aging and is influenced by inflammation. Applying a Research Domain Criteria (RDoC) Initiative perspective, we then review work examining how dopaminergic signaling affects these domains, specifically focusing on Cognitive, Positive Valence, and Sensorimotor Systems. We propose a unified model incorporating the effects of aging and low-grade inflammation on dopaminergic functioning, with a resulting negative effect on cognition, reward processing, and motor function. Interplay between these systems may influence development of a depressive phenotype, with an initial deficit in one domain reinforcing decline in others. This model extends RDoC concepts into late-life depression while also providing opportunities for novel and personalized interventions.
登录
查看更多内容
影响因子：
6.6
作者：
Alexopoulos, George S.;Hoptman, Matthew J.;Yuen, Genevieve;Kanellopoulos, Dora;Seirup, Joanna K.;Lim, Kelvin O.;Gunning, Faith M.
通讯作者：
Gunning, Faith M.
影响因子：
4.2
作者：
Backman, Lars;Karlsson, Sari;Nyberg, Lars
通讯作者：
Nyberg, Lars
影响因子：
10.6
作者：
Capuron, Lucile;Schroecksnadel, Sebastian;Fuchs, Dietmar
通讯作者：
Fuchs, Dietmar
影响因子：
7.2
作者：
Brown, Patrick J.;Liu, Xinhua;Roose, Steven P.
通讯作者：
Roose, Steven P.
影响因子：
--
作者：
Capuron L;Pagnoni G;Drake DF;Woolwine BJ;Spivey JR;Crowe RJ;Votaw JR;Goodman MM;Miller AH
通讯作者：
Miller AH