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.

关于哪种心理机制是介导SSRI治疗结果的根本不确定性以及其疗效的广泛差异，引起了更多的问题，但尚未解决。由于主观情绪状态是一种抽象的科学构造，只能通过人类的自我报告获得，并且可能涉及来自多个自上而下和自下而上的信号的输入，因此很难模拟SSRI与该过程交互作用的级别。越来越多的翻译证据表明，5-羟色胺在调节行动选择，情感和社会认知的情境相关参数方面具有作用。并同时支持学习机制，从而提高适应性和行为灵活性。我们研究了理论基础，生态有效性，这些构建体之间的相互作用以及它们如何发挥或不发挥临床益处。具体来说，我们弥合了不同研究领域之间的关键差距，尤其是动物模型和人类临床试验的发现之间的鸿沟，而这些研究似乎常常表现出无法调和的差异。在确定SSRI如何发挥作用时，我们的方法研究了5-HT神经元的内源性功能，5-HT操纵如何在不同情况下影响行为，以及它们如何在人类中发挥治疗作用-可能阐明了翻译模型的问题，等级机制，具体变量和社会认知。