CLOCK and major depressive disorder: As demonstrated before, these disorders appear to be in a reversed order relative to the development of the limbic system, starting with the decoupling of the amygdala in CDR 1 (i.e., depression), then of the NbM and prefrontal cortex (i.e., fears, delusions) in CDR 2, and, finally, of the SCN and HTPAG axis in CDR 3 (i.e., sundowning syndrome, wandering, aggression, disruption of the biological clock and circadian rhythm, and so on) [180,181].