Abstract
Major depressive disorder (MDD) is characterized by abnormal resting-state functional connectivity (RSFC), especially in medial prefrontal cortical (MPFC) regions of the default network. However, prior research in MDD has not examined dynamic changes in functional connectivity as networks form, interact, and dissolve over time. We compared unmedicated individuals with MDD (n=100) to control participants (n=109) on dynamic RSFC (operationalized as SD in RSFC over a series of sliding windows) of an MPFC seed region during a resting-state functional magnetic resonance imaging scan. Among participants with MDD, we also investigated the relationship between symptom severity and RSFC. Secondary analyses probed the association between dynamic RSFC and rumination. Results showed that individuals with MDD were characterized by decreased dynamic (less variable) RSFC between MPFC and regions of parahippocampal gyrus within the default network, a pattern related to sustained positive connectivity between these regions across sliding windows. In contrast, the MDD group exhibited increased dynamic (more variable) RSFC between MPFC and regions of insula, and higher severity of depression was related to increased dynamic RSFC between MPFC and dorsolateral prefrontal cortex. These patterns of highly variable RSFC were related to greater frequency of strong positive and negative correlations in activity across sliding windows. Secondary analyses indicated that increased dynamic RSFC between MPFC and insula was related to higher levels of recent rumination. These findings provide initial evidence that depression, and ruminative thinking in depression, are related to abnormal patterns of fluctuating communication among brain systems involved in regulating attention and self-referential thinking.
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Acknowledgements
We thank Alfonso Nieto-Castanon for valuable discussion of analytic approach, and Min Su Kang for help in manuscript preparation. This work was partially supported by the Rappaport Mental Health Research Fellowship and National Institute of Mental Health (NIMH) grant F32 MH106262 awarded to RHK, NIMH grant R00 MH094438 awarded to DGD, NIMH grants R21 MH094781 and R21 MH094781 S1 awarded to MS and GD, and NIMH grants R01 MH068376 and R01 MH101521 awarded to DAP.
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Kaiser, R., Whitfield-Gabrieli, S., Dillon, D. et al. Dynamic Resting-State Functional Connectivity in Major Depression. Neuropsychopharmacol 41, 1822–1830 (2016). https://doi.org/10.1038/npp.2015.352
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DOI: https://doi.org/10.1038/npp.2015.352
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