RG 5187/1: Towards precision psychotherapy for non-respondent patients: From signatures to predictions to clinical utility (SP 7)

Tailoring a treatment for mental disorders to individual patient characteristics is the aim of precision psychiatry and psychotherapy. This approach requires powerful predictors for the outcome of a given treatment on a specific patient. Previous research demonstrated that emotion regulation is central to both psychopathology and cognitivebehavior
therapy (CBT) and that the anterior cingulate cortex (ACC) is a crucial hub region for emotion regulation by its integration in several core brain networks. We propose that a dedicated systems-driven perspective will enable us to develop neuroimaging-derived biomarkers capable of predicting (non-)response to CBT for internalizing disorders. In particular, our SP will optimize ACC predictor information by employing three sophisticated methods: i) an efficient gradient of brain connectivity encoding alterations in the neural basis of explicit-controlled and implicit-automatic emotion regulation, ii) a graph-theoretical characterization of ACC networks and iii) a Bayesian hierarchical modelling approach to networks focusing on the ACC hub. We will train and fine tune our predictive models on three retrospective datasets used within the Research Unit, and then test their prediction accuracies both retrospectively but also on the prospective, independent dataset collected by SP1. Together, this approach allows us to test the core hypothesis that a sophisticated ensemble learning strategy based on several metrics for ACC network integration will achieve high accuracy for predicting CBT non-response. Additionally, results from this project will be returned into the Research Unit, by providing an optimal composition of ACCcentered system characteristics to SP2, by comparing our predictive performance with other neuroimaging-based predictors from SP8 and SP9 and by investigating whether our predictive model is associated with markers based on emotion-regulation strategies and psychophysiological markers of emotion regulation from SP4 and SP5. Overall, by applying methodological improvements and a clear
systems-perspective on the ACC, we aim to construct a predictor of CBT non-response that will demonstrate powerful prediction performance while at the same time providing high reliability and good predictor interpretability.