Molecular and neural circuit mechanisms of parvalbumin (PV) neurons in depression: Insights and advances

Interest in parvalbumin (PV) neurons has surged in recent years, driven by new insights into their role in the pathogenesis of depression. As a key class of γ-aminobutyric acid (GABA)-ergic interneurons, PV neurons have emerged as critical regulators of excitatory-inhibitory (E/I) balance, a core mechanism disrupted in depression. Growing evidence links PV neuron dysfunction to mood disturbances and cognitive impairments in depression. Recent studies highlight molecular alterations in PV neurons, including gene regulation, epigenetic modifications, and neurotransmitter/receptor imbalances, as well as circuit dysfunctions in the medial prefrontal cortex, hippocampus, and amygdala in depression. Interventions targeting PV neurons, such as pharmacological agents, neurotrophic factor modulation, and neuromodulation, show promise in restoring function. This review summarizes current advances in the molecular and circuit mechanisms of PV neuron dysfunction in depression, with the aim of providing a useful reference for future related studies.