{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:21:13Z","timestamp":1787908873300,"version":"build-2784847793"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003785","name":"Guangdong Medical Research Foundation","doi-asserted-by":"publisher","award":["B2026427"],"award-info":[{"award-number":["B2026427"]}],"id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2026,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Major depressive disorder (MDD) involves network\u2010level abnormalities that may reflect dysfunction in catecholaminergic nuclei, particularly the substantia nigra (SN) and locus coeruleus (LC), which regulate cortical gain and signal\u2010to\u2010noise ratio. However, whether MRI\u2010derived SN\/LC phenotypes are linked to depressive symptom severity through functional connectivity pathways in young individuals with MDD remains unclear. We studied 84 young participants (MDD,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200946; controls,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200938). MRI measures were extracted from the bilateral SN and LC using neuromelanin\u2010sensitive magnetization transfer contrast (MTC) imaging and iron\u2010sensitive quantitative susceptibility mapping (QSM). Seed\u2010to\u2010voxel analyses assessed associations between these phenotypes and resting\u2010state functional connectivity. Graph\u2010theoretical analyses extended functional connectivity findings to global network topology. Mediation analyses tested whether functional connectivity linked SN\/LC MRI phenotypes to Hamilton Depression Rating Scale scores within the MDD group. Multiple comparisons were controlled using false discovery rate (FDR) at\n                    <jats:italic>q<\/jats:italic>\n                    &lt;\u20090.05. Compared with controls, the MDD group exhibited reduced bilateral SN volume on QSM and decreased LC signal intensity on MTC. Neuromelanin\u2010 and iron\u2010sensitive phenotypes showed distributed functional connectivity associations involving frontal, sensorimotor, precuneus, and cerebellar regions. Bilateral SN susceptibility showed diagnosis\u2010dependent associations with global efficiency. Mediation analyses identified four candidate right LC functional connectivity pathways linking SN\/LC qMRI phenotypes to HAMD scores, mainly involving right LC connectivity with the left precuneus, right paracentral lobule, and cerebellum.SN\/LC catecholaminergic MRI phenotypes are associated with depressive severity and right LC\u2010centered functional connectivity, supporting candidate circuit\u2010level associations linking brainstem neuromodulatory phenotypes to clinical expression in MDD.\n                  <\/jats:p>","DOI":"10.1002\/hbm.70632","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T02:26:15Z","timestamp":1787106375000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Candidate Right Locus Coeruleus\u2010Centered Symptom Pathways in Young Major Depressive Disorder: A Multimodal Magnetic Resonance Imaging Study"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1431-9885","authenticated-orcid":false,"given":"Zesong","family":"Yuan","sequence":"first","affiliation":[{"name":"First Clinical Medical College Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"First Clinical Medical College Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danian","family":"Li","sequence":"additional","affiliation":[{"name":"Cerebropathy Center The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohua","family":"Cheng","sequence":"additional","affiliation":[{"name":"First Clinical Medical College Guangzhou University of Chinese Medicine  Guangzhou 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