Targeting Mechanisms of Change as a Path to Precision Psychotherapy in Community Settings

Major depression remains an urgent public health challenge with detrimental long-term effects. Despite tremendous scientific progress, most depressed individuals lack access to high-quality psychotherapies, and even when treated, overall response rates remain stagnant. Uncovering the mechanisms underlying change in psychotherapy can guide the development of simple and scalable interventions that target these mechanisms. A multimodal approach—integrating brain-based mechanisms, neuroscience tools, and artificial intelligence methods—offers a powerful framework for mechanisms research. Novel methods can improve precise detection of changes in candidate mechanism (brain functions, behavior, language and voice). A multimodal approach requires strong interdisciplinary teams that include clinicians, psychotherapy researchers, neuroscientists, computational experts, and community stakeholders. Insights from these collaborations can inform ‘precision psychotherapy’ – tailoring targeted interventions to each patient’s needs and circumstances. A key future direction is improving scalability of treatment decision rules (TDRs) – a data-driven approach to assign patients to their optimal intervention. TDRs should inform assignment to simple and scalable interventions, such as remotely delivered psychotherapies and digital interventions. Through research-practice networks, these innovations can be implemented in community settings and delivered to underserved populations. I describe these processes, provide examples of our own and others’ work, outline challenges, and propose future directions for mechanisms research.