Default mode network functional connectivity following treatment with conventional antidepressants and (es)ketamine...

Antidepressant treatments, including conventional antidepressants and (es)ketamine, may reverse default mode network (DMN) resting-state functional connectivity (rsFC) alterations related to major depressive disorder (MDD). Despite these agents having distinct initial action mechanisms, both likely share downstream effects that lead to structural and functional adaptations in MDD-related neural circuits. Examining the effects of these agents on DMN rsFC can provide insights into network-level effects, advance understanding of network-level mechanisms of treatment response, and generate hypotheses regarding potential neurobiological differences between MDD and treatment-resistant depression populations. A systematic search was performed to retrieve studies investigating changes in DMN rsFC following treatment with conventional antidepressants and (es)ketamine in MDD, including the association with clinical outcomes. Nineteen studies were included, 13 administered conventional antidepressants (N = 546), and six intravenous ketamine (N = 247). Conventional antidepressants were associated with heterogeneous changes in DMN rsFC, some of which related to clinical improvements. Conversely, ketamine mostly related with reductions in DMN rsFC, particularly in DMN-limbic connectivity. While interpretations of current findings are limited by heterogeneity in study populations, treatment regimens, and timing assessments, findings suggest that these agents exhibit mostly distinct patterns of DMN modulation, and that differential effects on DMN rsFC associate with clinical improvements.