Zilcha-Mano Sigal, Solomonov Nili, Posner Jonathan E, Roose Steven P, Rutherford Bret R
Department of Psychology, University of Haifa, Mount Carmel, Haifa 31905, Israel.
Weill Cornell Institute of Geriatric Psychiatry, Weill Cornell Medicine, White Plains, NY 10605, USA.
J Pers Med. 2022 Jul 23;12(8):1197. doi: 10.3390/jpm12081197.
Identifying individual-specific mechanisms of action may facilitate progress toward precision medicine. Most studies seeking to identify mechanisms of action collapse together two distinct components: pre-treatment trait-like characteristics differentiating between individuals and state-like characteristics changing within each individual over the course of treatment. We suggest a conceptual framework highlighting the importance of studying interactions between trait-like and state-like components in the development of moderated mediation models that can guide personalized targeted interventions. To facilitate implementation of this framework, two empirical demonstrations are presented from a recent clinical trial and neuroimaging study. The first examines limbic reactivity during an emotional face task; the second concerns striatal activation in a monetary reward task. In both tasks, considering the interaction between trait-like and state-like components predicted treatment outcome more robustly than did the trait-like or state-like components examined individually. These findings suggest that the extent to which state-like modulation of neural activations can serve as a potential treatment target depends on the pre-treatment, trait-like levels of activation in these regions. Thus, the interaction between trait-like and state-like components can serve as a promising path to the development of personalized interventions within a precision medicine framework in which mechanisms of action are individual-specific.
识别个体特异性的作用机制可能有助于推动精准医学的发展。大多数旨在识别作用机制的研究将两个不同的组成部分混为一谈：区分个体的治疗前类似特质的特征以及在每个个体的治疗过程中发生变化的类似状态的特征。我们提出了一个概念框架，强调在构建能够指导个性化靶向干预的调节中介模型时，研究类似特质和类似状态成分之间相互作用的重要性。为了便于实施这一框架，我们从最近的一项临床试验和神经影像学研究中给出了两个实证示例。第一个示例考察了在情绪面孔任务中的边缘系统反应性；第二个示例涉及金钱奖励任务中的纹状体激活。在这两个任务中，考虑类似特质和类似状态成分之间的相互作用比单独考察类似特质或类似状态成分更能有力地预测治疗结果。这些发现表明，神经激活的类似状态调节作为潜在治疗靶点的程度取决于这些区域治疗前类似特质的激活水平。因此，类似特质和类似状态成分之间的相互作用可以作为在精准医学框架内开发个性化干预措施的一条有前景的途径，在该框架中作用机制是个体特异性的。
