Microglia are best known as the immune cells of the brain, but emerging data indicate that they also influence brain development, synaptic plasticity, neurogenesis, memory, and mood under quiescent physiological conditions.

Deviation from microglial homeostasis, caused either by microglial activation during inflammatory conditions (e.g., infections, stress, stroke, or neurodegenerative diseases) or by microglial decline and senescence (e.g., during aging or chronic unpredictable stress), can lead to depression.

Conventional antidepressant drugs and electroconvulsive therapy modulate microglial structure and function, suggesting a novel mechanism of action for these treatments.

Microglia represent a promising therapeutic target for the treatment of depression; either microglia-suppressing or -stimulating drugs can serve as antidepressants, depending on the microglial status of the patient.