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However, there are no high-resolution characterizations of the role of their subregions in the whole brain network (connectome). Connectomic examination of these subregions can uncover disorder-related patterns that are otherwise missed when treated as single structures. 38 MDD patients and 40 healthy controls (HC) underwent anatomical and diffusion imaging using 7-Tesla MRI. Whole-brain segmentation was performed along with hippocampus and amygdala subregion segmentation, each representing a node in the connectome. Graph theory analysis was applied to examine the importance of the limbic subregions within the brain network using centrality features measured by<jats:italic>node strength<\/jats:italic>(sum of weights of the node\u2019s connections),<jats:italic>Betweenness<\/jats:italic>(number of shortest paths that traverse the node), and<jats:italic>clustering coefficient<\/jats:italic>(how connected the node\u2019s neighbors are to one another and forming a cluster). Compared to HC, MDD patients showed decreased node strength of the right hippocampus cornu ammonis (CA) 3\/4, indicating decreased connectivity to the rest of the brain, and decreased clustering coefficient of the right dentate gyrus, implying it is less embedded in a cluster. Additionally, within the MDD group, the greater the embedding of the right amygdala central nucleus (CeA) in a cluster, the greater the severity of depressive symptoms. The altered role of these limbic subregions in the whole-brain connectome is related to diagnosis and depression severity, contributing to our understanding of the limbic system involvement in MDD and may elucidate the underlying mechanisms of depression.<\/jats:p>","DOI":"10.1038\/s41398-022-01976-0","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T10:04:29Z","timestamp":1652954669000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Altered hippocampus and amygdala subregion connectome hierarchy in major depressive disorder"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3278-9264","authenticated-orcid":false,"given":"Yael","family":"Jacob","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5862-6650","authenticated-orcid":false,"given":"Laurel S.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah B.","family":"Rutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priti","family":"Balchandani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-1242","authenticated-orcid":false,"given":"James W.","family":"Murrough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"1976_CR1","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1001\/archpsyc.62.6.617","volume":"62","author":"RC Kessler","year":"2005","unstructured":"Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. 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The patents have been licensed to GE Healthcare, Siemens AG, and Philips international. Dr. Balchandani receives royalty payments relating to these patents. In the past 5 years, Dr. Murrough has provided consultation services and\/or served on advisory boards for Boehringer Ingelheim, Clexio Biosciences, Engrail Therapeutics, FSV7, Global Medical Education (GME), Otsuka, and Sage Therapeutics. Dr. Murrough is named on a patent-pending for neuropeptide Y as a treatment for mood and anxiety disorders and on a patent pending for the use of KCNQ channel openers to treat depression and related conditions. The Icahn School of Medicine (employer of Dr. Murrough) is named on a patent and has entered into a licensing agreement and will receive payments related to the use of ketamine or esketamine for the treatment of depression. The Icahn School of Medicine is also named on a patent related to the use of ketamine for the treatment of PTSD. Dr. Murrough is not named on these patents and will not receive any payments. No other authors reported biomedical financial interests or potential conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"209"}}