The changes in morphology combined with the upregulation of synaptic markers in TREK‐1 knockdown and TREK‐1 inhibited mice, consistent with the observations of treatment with spadin,19 strongly suggested that the TREK‐1 channel may be a potential therapeutic target of depression, and TREK‐1 inhibitors, such as spadin and SID1900, may be potent up‐regulators of neuronal functions. This evidence concerns the gene KCNK2 and depressive disorder.