ArticlePsychological medicine2025
Cortical morphometric gradients reveal molecular and cognitive underpinnings of bipolar disorder.
Article in Psychological medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundStructural brain alterations in bipolar disorder (BD) have been widely reported, yet the hierarchical organization of cortical morphometric networks and their molecular and cognitive underpinnings remain unclear.
methodsWe applied the morphometric inverse divergence (MIND) network approach to structural MRI data from 49 BD patients and 119 healthy controls. 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.
resultsBipolar 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
conclusionsThese 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.
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