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Conclusions The convergence of ferroptosis, mitochondrial damage, and cerebral metabolic remodeling establishes a self-amplifying pathological triad in depression through three interlocked mechanisms: (1) GPX4 inactivation-driven lipid peroxidation disrupts neuronal membrane integrity while impairing mitochondrial respiratory chain complexes (I/III/IV) and releasing DAMPs that activate microglial NLRP3 inflammasomes

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The underlying cause of deficiency is the most important determinant