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Principal MIND gradients were derived using diffusion map embedding, followed by multiscale analyses linking gradient alterations to neurotransmitter systems, cognitive-behavioral domains, and transcriptomic profiles from the Allen Human Brain Atlas. Validation was performed in three independent, cross-scanner, cross-race, and cross-age validation datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291725102705_sec3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Bipolar disorder patients showed significant principal gradient alterations in the left rostral middle frontal and lateral occipital cortices, with network-level decreases in the ventral attention and motor networks and increases in frontoparietal and visual networks. Gradient alterations spatially correlated with acetylcholine (VAChT) and GABA (GABA\n                      <jats:sub>A\/BZ<\/jats:sub>\n                      ) systems, and were associated with cognitive processes involving executive control and visual attention. Transcriptomic analyses identified gene sets enriched for BD-related GWAS loci, expressed predominantly in excitatory and inhibitory neurons, astrocytes, and oligodendrocytes, with preferential enrichment in cortical layers III-IV and developmental windows spanning early fetal to young adulthood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291725102705_sec4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings reveal disrupted hierarchical cortical organization in BD and link macroscale morphometric alterations to specific neurotransmitter systems and transcriptional architectures. The MIND gradient emerges as a potential biomarker bridging structural disruptions with molecular and cognitive mechanisms in BD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s0033291725102705","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T10:30:43Z","timestamp":1766053843000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":4,"title":["Cortical morphometric gradients reveal molecular and cognitive underpinnings of bipolar disorder"],"prefix":"10.1017","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3553-1520","authenticated-orcid":false,"given":"Rui","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/007mrxy13","id-type":"ROR","asserted-by":"publisher"}],"name":"West China Hospital of Sichuan 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