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350 REVERSIBLE DISORDERS OF BRAIN DEVELOPMENT2002), maladaptive emotional, cognitive, and behavioral outcomes, and greatersusceptibility to PTSD and other psychiatric disturbance (Southwick et al., 2005).Severe Childhood StressChildhood adversity, in the form of trauma, neglect, deprivation, or abuse, maybe especially harmful during critical periods in brain development. It is well knownthat external stressors impact the structure, organization, and activity of the CNS(e.g. Heim & Nemeroff, 2002). Early developmental stress is associated with bothshort- and long-term neurobiological changes (reviewed in Heim & Nemeroff,2002) and related emotional, cognitive, and behavioral alterations.Chronic stress created by an unstable childhood (e.g., maternal separation,deprivation, neglect, physical or sexual abuse, or other early trauma) can causeallostatic load, which results in neurobiological alterations that can be long-lasting.Studies investigating the effects of early social environment have shown thatstress can promote potentially permanent alterations in brain regions and neurotransmittersystems related to the pathophysiology of depression and PTSD (reviewedin Heim & Nemeroff, 2002, and Kaufman & Charney, 2001). Furthermore,it is likely that the neurobiological alterations associated with early adverse experienceconfer vulnerability, or sensitize the organism to later development of stressrelatedmental disorders (Charney, 2004). Due in part to these neurobiologicalanomalies, childhood abuse is correlated with increased incidence of psychiatricillnesses such as major depression, PTSD, and other mood and anxiety disorders(Bremner et al., 1993; De Bellis, 2001; Kaufman et al., 1998). It is thought thatthese structural and functional neurobiological alterations can be reversed by anenriched caregiving environment, through pharmacological interventions (Kaufmanet al., 1998), and possibly also through psychological or psychotherapeuticintervention.Extensive rodent studies by Meaney and colleagues have explored the effects(both protective and deleterious) of early environment on neurobiological systems.They found that postnatal maternal separation in rat pups increases hypothalamiccorticotropin-releasing factor (CRF) gene expression and hypothalamic-pituitaryadrenergic(HPA) axis response to stress, along with fear-related behavioralchanges (e.g., exploration of environment, appetitive behavior, startle response).However, when rat pups were exposed to an enriched environment (i.e., increasedhandling), the neurobiological changes reversed (Francis et al., 2002). Meaneyand colleagues also found that natural variations in maternal care of rat pups (i.e.,high and low levels of licking/grooming and arched-back nursing) produced paralleldifferences in HPA axis functioning in their offspring. It is also known thatearly mothering impacts the development and function of the hippocampus (Liuet al., 2000). Rodent mothers who displayed increased caregiving behaviors (i.e.,licking/grooming and arched-backed nursing) had offspring with increased hippocampalsynaptogenesis and improved spatial learning and memory (Bredy et al.,