The neurobiology of treatment-resistant depression: A systematic review of neuroimaging studies

Treatment-resistant depression (TRD) is a debilitating condition associated with higher medical costs, increased illness burden, and reduced quality of life compared to non-treatment-resistant major depressive disorder (MDD). The question arises whether TRD can be considered a distinct MDD sub-type based on neurobiological features. To answer this question we conducted a systematic review of neuroimaging studies investigating the neurobiological differences between TRD and non-TRD. Our main findings are that patients with TRD show 1) reduced functional connectivity (FC) within the default mode network (DMN), 2) reduced FC between components of the DMN and other brain areas, and 3) hyperactivity of DMN regions. In addition, aberrant activity and FC in the occipital lobe may play a role in TRD. The main limitations of most studies were related to inherent confounding factors for comparing TRD with non-TRD, such as differences in disease chronicity/severity and medication history. Future studies may use prospective longitudinal neuroimaging designs to delineate which effects are present in treatment-naive patients and which effects are the result of disease progression.

Automated summary

Our systematic review of neuroimaging studies reveals neurobiological differences between patients with Treatment-resistant depression (TRD) and non-TRD, including reduced functional connectivity within the default mode network (DMN), reduced connectivity between DMN and other brain areas, and hyperactivity of DMN regions. Aberrant activity and connectivity in the occipital lobe may also play a role in TRD. However, limitations in existing studies highlight the need for prospective longitudinal neuroimaging designs to better understand the effects of disease progression in TRD.