Predicting Antidepressant Treatment Response Using Functional Brain Controllability Analysis

Introduction: For decades, predicting response to the antidepressant medication has been a critical unmet need in depression treatment in clinic, and a technical challenge in depression research. Methods: In this study, a recently developed functional brain network controllability (fBNC) analysis approach was employed to identify the antidepressant treatment responders and nonresponders from depression patients at the pretreatment period. The fBNC, which captures the ability of brain regions to guide the brain's behavior from an initial state to a desired state with suitable choice of inputs, may provide valuable features for antidepressant response prediction. The performance of prediction was evaluated using resting-state functional magnetic resonance imaging data collected from a 6-week longitudinal clinical trial with escitalopram in treating unmedicated depression patients (n = 20). Treatment outcomes were assessed using the Hamilton Depression Rating Scale (HAMD) scores. Patients were considered as the treatment responders if their post-treatment HAMD scores were decreased by 50% or more at 6 weeks post-treatment. Results: Results showed significantly larger global average controllability and lower global modal controllability, greater regional average controllability, and smaller regional modal controllability of default mode network in treatment responders compared with the treatment nonresponders at the pretreatment period. By performing optimal control analysis, our results showed no significant difference of the neuromodulation effects between the treatment responders and nonresponders. Discussion: Our results suggest that the fBNC measures may be utilized as novel biomarkers to predict antidepressant response on depression and provide theoretical support to employ neuromodulation for treating antidepressant nonresponders. In this study, by employing the novel functional brain controllability analysis on top of the brain connectivity network, we identified a set of biomarkers to identify the groups of depressive patients who responded to the antidepressant treatments from those who did not. We further provided the theoretical support to utilize neuromodulation for treating antidepressant nonresponders. These findings have clinical implications as accurate identification of antidepressant treatment response before starting the treatment may reduce patients' suffering and costs and increase the treatment outcomes by adjusting and personalizing the treatment protocol.