Functional MRI markers for treatment-resistant depression: Insights and challenges.

Imaging studies of treatment-resistant depression (TRD) have examined brain activity, structure, and metabolite concentrations to identify critical areas of investigation in TRD as well as potential targets for treatment interventions. This chapter provides an overview of the main findings of studies using three imaging modalities: structural magnetic resonance imaging (MRI), functional MRI (fMRI), and magnetic resonance spectroscopy (MRS). Decreased connectivity and metabolite concentrations in frontal brain areas appear to characterize TRD, although results are not consistent across studies. Treatment interventions, including rapid-acting antidepressants and transcranial magnetic stimulation (TMS), have shown some efficacy in reversing these changes while alleviating depressive symptoms. However, comparatively few TRD imaging studies have been conducted, and these studies often have relatively small sample sizes or employ different methods to examine a variety of brain areas, making it difficult to draw firm conclusions from imaging studies about the pathophysiology of TRD. Larger studies with more unified hypotheses, as well as data sharing, could help TRD research and spur better characterization of the illness, providing critical new targets for treatment intervention.