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Dynamic functional connectivity is a novel tool with little application in affective disorders to date, and holds the potential to unravel fluctuations in connectivity strength over time in major depression. We assessed stability of connectivity in major depression between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), key nodes in the DMN that are implicated in ruminative cognitions. Functional connectivity stability between the mPFC and PCC over the course of a resting-state functional magnetic resonance imaging (fMRI) scan was compared between medication-free patients with major depression and healthy controls matched for age, sex and handedness. We tested replicability of the results in an independent sample using multi-echo resting-state fMRI. The primary sample included 20 patients and 19 controls, while the validation sample included 19 patients and 19 controls. Greater connectivity variability was detected in major depression between mPFC and PCC. This was demonstrated in both samples indicating that the results were reliable and were not influenced by the fMRI acquisition approach used. Our results demonstrate that alterations within the DMN in major depression go beyond changes in connectivity strength and extend to reduced connectivity stability within key DMN regions. Findings were robustly replicated across two independent samples. Further research is necessary to better understand the nature of these fluctuations in connectivity and their relationship to the aetiology of major depression.<\/jats:p>","DOI":"10.1038\/tp.2017.40","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T09:42:21Z","timestamp":1493113341000},"page":"e1105-e1105","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":198,"title":["Instability of default mode network connectivity in major depression: a two-sample confirmation study"],"prefix":"10.1038","volume":"7","author":[{"given":"T","family":"Wise","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Marwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A M","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Herane-Vives","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Joules","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D J","family":"Lythgoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W-M","family":"Luh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S C R","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A H","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Cleare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Arnone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,25]]},"reference":[{"key":"BFtp201740_CR1","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1001\/jama.289.23.3095","volume":"289","author":"RC Kessler","year":"2003","unstructured":"Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR et al. 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DJL has consulted for Ixico PLC. AHY has given paid lectures and sits on advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders; is the lead investigator for the Embolden Study (AZ), BCI Neuroplasticity study and Aripiprazole Mania Study and investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth; and has received grant funding from the National Institute of Mental Health (USA); Canadian Institutes of Health Research (Canada); National Alliance for Research on Schizophrenia and Depression (USA); Stanley Medical Research Institute (USA); Medical Research Council (UK); Wellcome Trust (UK); Royal College of Physicians (Edinburgh); British Medical Association (UK); University of British Columbia-Vancouver General Hospital Foundation (Canada); Western Economic Diversification Canada (Canada); Canadian Cardiovascular Society Depression Research Fund (Canada); Michael Smith Foundation for Health Research (Canada); and National Institute for Health Research (UK). AMP is supported by Bionomics Limited. DA has received travel grants from Janssen-Cilag and Servier. SCRW has received grant funding from the Medical Research Council (UK); Wellcome Trust (UK); National Institute for Health Research (UK) and support for investigator-led studies from Takeda, Pfizer, Lundbeck, P1Vital, Roche and Eli Lilly. The remaining authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}