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To date, emerging evidence from behavior and psychology suggests the possibility of underlying neurobiological mechanisms in transdiagnostic depression. This study aims to identify predictive signatures of depression severity across MDD and PTSD using a whole\u2010brain connectivity machine learning analysis based on resting\u2010state functional magnetic resonance imaging (rs\u2010fMRI). Patients with MDD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200984) and PTSD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200965), all medication\u2010free at the time of enrollment, underwent rs\u2010fMRI scans along with a battery of clinical assessments. Using a multivariate machine learning approach, we applied sparse connectome predictive modeling to identify a functional connectivity signature that predicts individual depression severity, as assessed by Hamilton Depression Rating Scale\u201017 items. The cross\u2010validated model explained 42% of the variance in depression severity across MDD and PTSD. The identified connectome signature predominantly involved regions in the fronto\u2010limbic circuit (e.g., middle frontal gyrus and temporal pole), subcortical areas (e.g., hippocampal, caudate, and brainstem), and the cerebellum. Our findings highlight diffuse whole\u2010brain dysfunction patterns associated with depressive symptom severity, emphasizing the importance of transdiagnostic research in understanding the neurobiological mechanisms underlying key clinical features across disorders.\n                  <\/jats:p>","DOI":"10.1111\/ejn.70271","type":"journal-article","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T10:40:12Z","timestamp":1759574412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Whole\u2010Brain Connectome\u2010Wide Signature of Transdiagnostic Depression Severity Across Major Depressive Disorder and Posttraumatic Stress Disorder"],"prefix":"10.1111","volume":"62","author":[{"given":"Runnan","family":"Yang","sequence":"first","affiliation":[{"name":"Mental Health Center West China Hospital of Sichuan University  Chengdu Sichuan China"},{"name":"Huaxi Brain Research Center West China Hospital of 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