Roberts Clark, Sahakian Barbara J, Robbins Trevor W
Department of Psychiatry, University of Cambridge, Cambridge, UK; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Department of Psychiatry, University of Cambridge, Cambridge, UK; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Neurosci Biobehav Rev. 2020 Dec;119:138-167. doi: 10.1016/j.neubiorev.2020.09.001. Epub 2020 Sep 12.
Uncertainty regarding which psychological mechanisms are fundamental in mediating SSRI treatment outcomes and wide-ranging variability in their efficacy has raised more questions than it has solved. Since subjective mood states are an abstract scientific construct, only available through self-report in humans, and likely involving input from multiple top-down and bottom-up signals, it has been difficult to model at what level SSRIs interact with this process. Converging translational evidence indicates a role for serotonin in modulating context-dependent parameters of action selection, affect, and social cognition; and concurrently supporting learning mechanisms, which promote adaptability and behavioural flexibility. We examine the theoretical basis, ecological validity, and interaction of these constructs and how they may or may not exert a clinical benefit. Specifically, we bridge crucial gaps between disparate lines of research, particularly findings from animal models and human clinical trials, which often seem to present irreconcilable differences. In determining how SSRIs exert their effects, our approach examines the endogenous functions of 5-HT neurons, how 5-HT manipulations affect behaviour in different contexts, and how their therapeutic effects may be exerted in humans - which may illuminate issues of translational models, hierarchical mechanisms, idiographic variables, and social cognition.
关于哪些心理机制在介导选择性5-羟色胺再摄取抑制剂（SSRI）治疗效果中起根本作用的不确定性，以及它们疗效的广泛变异性，引发的问题比解决的问题更多。由于主观情绪状态是一种抽象的科学概念，只能通过人类的自我报告获得，并且可能涉及多个自上而下和自下而上信号的输入，因此很难模拟SSRI在哪个层面与这一过程相互作用。越来越多的转化证据表明，血清素在调节行动选择、情感和社会认知的情境依赖参数方面发挥作用；同时支持学习机制，促进适应性和行为灵活性。我们研究这些概念的理论基础、生态效度及其相互作用，以及它们如何可能产生或不产生临床益处。具体而言，我们弥合了不同研究方向之间的关键差距，特别是动物模型和人类临床试验的结果，这些结果往往似乎存在无法调和的差异。在确定SSRI如何发挥作用时，我们的方法研究5-羟色胺（5-HT）能神经元的内源性功能、5-HT操作如何在不同情境中影响行为，以及它们的治疗效果在人类中可能如何发挥——这可能阐明转化模型、层级机制、个体变量和社会认知等问题。
