CCKergic System, Hypothalamus-Pituitary-Adrenal (HPA) Axis, and Early-Life Stress (ELS)

Early-life exposure to adverse experience or stress, simply termed early-life stress (ELS), is a worldwide problem that has a significantly negative impact in human health [1, 2]. In the United States, about 50% of adults had experienced some kind of stress before age 18 [3], and up to 15-25% of adults had traumatic ELS such as sexual abuse [4]. Most ELS is parentsoriginated, such as neglect, maltreatment, and abuse [5, 6]. In addition to the immediate, dreadful, and destructive effects on a child’s life, ELS may produce a series of mental [7, 8], cardiovascular [9, 10], metabolic [11, 12], and many other types of disease [13, 14], at a later life stage. For example, adults who were sexually abused during childhood have a 5.7-fold increase in risk for drug abuse over those without ELS [7], and the prevalence of posttraumatic stress disorder (PTSD), a predominant form of anxiety disorders (ADs), is highly associated with ELS, with a 4-5 fold difference between adults with ELS and those without ELS [15]. Moreover, cognitive dysfunctions [16-18] such as learning and memory impairment [19-21] are also highly associated with ELS. Given that children, especially early adolescents, have a higher possibility to expose to a traumatic insult [22], adolescent trauma (AT) is an important risk factor for these post-ELS disorders.