CRH and major depressive disorder: These studies gave rise to “stress diathesis” or “two-hit” models of depression, which propose that the early trauma sensitizes underlying physiological stress-related systems [e.g., increase central corticotropin releasing factor (CRF) release or augment amygdala activation] so that when the individual is exposed to stressors in adolescence or beyond, they elicit enhanced and or unregulated stress responses that can trigger, segue into, or actually constitute the depressive episode (Gold et al., 1988; Schulkin et al., 1994; Heim et al., 2008).