HCN1 and major depressive disorder: However, it is noteworthy to highlight the upregulation of the hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1; Fig. 2b), an ion channel associated with stress-related disorders, including schizophrenia (Chen et al., 2022) and depression (Shah, 2012; C. S. Kim and Johnston, 2018).