Early life stress, HPA axis, and depression.

Abstract

Considerable evidence from various studies suggests a preeminent role for early adverse experiences in the development of psychopathology, especially depression. The most recent studies reviewed herein suggest that early life stressors are associated with an increased risk for mood disorders in adulthood. This review examines the emerging literature on the relationship between stress, hypothalamic-pituitary-adrenal (HPA) axis function, and depression and the role of early life stress as an important risk factor for HPA axis dysregulation. The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolemia and reduced inhibitory feedback. Moreover, HPA axis changes appear to be statedependent, tending to improve upon resolution of the depressive syndrome. Interestingly, persistent HPA hyperactivity has been associated with higher rates of relapse. These studies suggest that an evaluation of the HPA axis during antidepressant treatment may help identify patients who are at a higher risk for relapse. These findings suggest that this dysregulation of the HPA axis is partially attributable to an imbalance between glucocorticoid and mineralocorticoid receptors. Evidence has consistently demonstrated that glucocorticoid receptor function is impaired in major depression, but few studies have assessed the activity of mineralocorticoid receptors in depression. Thus, more studies are needed to elucidate this issue.

Early Life Stress Activates Glial Cells in the Hippocampus but Attenuates Cytokine Secretion in Response to an Immune Challenge in Rat Pups

“…Early life stress (ELS) is considered a risk factor for the development of psychopathologies such as anxiety and major depressive illness [1,2] and a contributor to the development of neurodegenerative disorders later in life [3]. Within the brain, ELS promotes a neuroinflammatory state [4], with patients who suffered ELS in childhood showing an increased cytokine response to psychological stressors [5].…”

Association between child maltreatment indicators and developmental problems in early childhood education

“…These data corroborate results found in previous studies that have indicated that the sequelae in different individuals vary from a few worrying symptoms to clinically relevant levels of maltreatment symptoms, and to the presence of severe psychiatric disorders. [14][15][16][17] Significant differences were also found in Internalizing Problems. For Externalizing Problems, there were no differences between the groups, even though the p value was close to significant.…”

“…32 This data can be considered significant if the investigations related to the prevalence of maltreatment in same-age children, recruited from the same region in the city, pointed to neglect. 2,20 Some studies suggest that maltreatment has caused depression and withdrawal, especially because these disorders are commonly associated with individuals' homeostatic imbalance 15 and can harm the brain structuring process, especially in children, during this critical period of their development. 18,19,32 Furthermore, depression and withdrawal, during childhood can lead to isolation, and therefore, generate, in the long-term, new problems with the child's social development as associated with suicide risk.…”

“…This condition would be continuous, with a continuous release of adrenocortical hormones (cortisol), which could result in the individual's homeostatic imbalance. 15 The imbalance caused by this process would result in damage, and the most severe could be experienced throughout the critical period of childhood. The development of the brain during this period is intense and usually implies changes in different parts of the brain, as part of the process of maturation.…”

Exogenous Cortisol Administration; Effects on Risk Taking Behavior, Exercise Performance, and Physiological and Neurophysiological Responses

“…Changes in risk related behavior are also time dependent (Henckens et al, 2012) and although we aimed to measure delayed effects of exogenous cortisol, it is possible that some rapid effects remained in some individuals and thus changes in reward based decision making might have been impaired in this instance (Koot et al, 2013). Further to this, HPA axis physiology is determined by previous stressful events associated with hypercortisolism (Herman and Cullinan, 1997; de Carvalho Tofoli et al, 2011) and, therefore, it has been hypothesized that endurance-trained individuals might develop adaptive mechanisms such as decreased sensitivity to cortisol to protect muscle and other glucocorticoid-sensitive tissues against this increased post-exercise cortisol secretion (Duclos et al, 2003). …”