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Functional connectivity changes with rapid remission from severe major depressive disorder

By Xiaoqian Xiao, Brandon Stephen Bentzley, Eleanor J Cole, Claudia Tischler, Katy H Stimpson, Dalton Duvio, James H. Bishop, Danielle D. DeSouza, Alan Schatzberg, Corey Keller, Keith D Sudheimer, Nolan R Williams

Posted 21 Jun 2019
bioRxiv DOI: 10.1101/672154

Major depressive disorder (MDD) is prevalent and debilitating, and development of improved treatments is limited by insufficient understanding of the neurological changes associated with disease remission. In turn, efforts to elucidate these changes have been challenging due to disease heterogeneity as well as limited effectiveness, delayed onset, and significant off-target effects of treatments. We recently developed a form of repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex (lDLPFC) that induces remission from MDD in 90% of individuals in 1-5 days (Stanford Accelerated Intelligent Neuromodulation Therapy, SAINT). This provides a new tool to begin exploring the functional connectivity (FC) changes associated with MDD remission. Herein, we report our investigation of the FC changes that occur following SAINT. Resting-state fMRI scans were performed before and after SAINT in 18 participants with severe, treatment-resistant MDD. FC was determined between regions of interest defined a priori by well-described roles in emotion regulation. Following SAINT, FC was significantly decreased between subgenual cingulate cortex (sgACC) and 3 of 4 default mode network (DMN) nodes. Significant reductions in FC were also observed between the following: DLPFC-striatum, DLPFC-amygdala, DMN-amygdala, DMN-striatum, and amygdala-striatum. Greater clinical improvements were correlated with larger decreases in FC between DLPFC-amygdala and DLPFC-insula, as well as smaller decreases in FC between sgACC-DMN. Greater clinical improvements were correlated with lower baseline FC between DMN-DLPFC, DMN-striatum, and DMN-ventrolateral prefrontal cortex. The multiple, significant reductions in FC we observed following SAINT and remission from depression support the hypothesis that MDD is a state of hyper-connectivity within these networks, and rapid decoupling of network nodes may lead to rapid remission from depression. ### Competing Interest Statement Dr. Bentzley receives consulting payments from Owl Insights.

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