Furthermore, decreased CHRM2 expression in cortex is associated with bipolar and major depressive disorders (Gibbons et al., 2009), and polymorphisms association studies support CHRM2 involvement in major depressive disorder (Comings et al., 2002), potentially implying Shh pathway activation in synaptopathies and neurological pathologies in humans. Here, CHRM2 is linked to major depressive disorder.