CRH and major depressive disorder: Interestingly, abnormal activation of the LC has been associated with the development of helpless behavior (Simson and Weiss, 1988; Vollmayr and Henn, 2003; Takase et al., 2005), and increased LC response to corticotropin-releasing factor (CRF) has been linked to depression (Bangasser et al., 2010).