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Abstract
Major depressive disorder (MDD) could be conceptualized as a distributed failure of ionic homeostasis.
- Genetic susceptibility, chronic stress, metabolic burden, and neuroinflammation may disrupt ion-channel systems in neurons and glial cells.
- Disruptions in calcium, potassium, chloride, and purinergic homeostasis could alter intrinsic excitability and synaptic integration.
- These disturbances are associated with excitation-inhibition imbalance, impaired plasticity, and corticolimbic network instability.
- Specific ion channels and glial mediators are implicated in the mechanisms underlying MDD.
- Ketamine-related mechanisms and chloride-restoring strategies may inform precision therapeutics for MDD.
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