Breakthroughs and challenges for generating brain network-based biomarkers of treatment response in depression

Treatment outcomes widely vary for individuals diagnosed with major depressive disorder, implicating a need for deeper understanding of the biological mechanisms conferring a greater likelihood of response to a particular treatment. Our improved understanding of intrinsic brain networks underlying depression psychopathology via magnetic resonance imaging and other neuroimaging modalities has helped reveal novel and potentially clinically meaningful biological markers of response. And while we have made considerable progress in identifying such biomarkers over the last decade, particularly with larger, multisite trials, there are significant methodological and practical obstacles that need to be overcome to translate these markers into the clinic. The aim of this review is to review current literature on brain network structural and functional biomarkers of treatment response or selection in depression, with a specific focus on recent large, multisite trials reporting predictive accuracy of candidate biomarkers. Regarding pharmaco- and psychotherapy, we discuss candidate biomarkers, reporting that while we have identified candidate biomarkers of response to a single intervention, we need more trials that distinguish biomarkers between first-line treatments. Further, we discuss the ways prognostic neuroimaging may help to improve treatment outcomes to neuromodulation-based therapies, such as transcranial magnetic stimulation and deep brain stimulation. Lastly, we highlight obstacles and technical developments that may help to address the knowledge gaps in this area of research. Ultimately, integrating neuroimaging-derived biomarkers into clinical practice holds promise for enhancing treatment outcomes and advancing precision psychiatry strategies for depression management. By elucidating the neural predictors of treatment response and selection, we can move towards more individualized and effective depression interventions, ultimately improving patient outcomes and quality of life.