Proof of Concept of the Contribution of the Interaction Between Trait-like and State-like Effects in Identifying Individual-Specific Mechanisms of Action in Biological Psychiatry.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.