Childhood stressful events, HPA axis and anxiety disorders

Abstract

Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic pituitary adrenal (HPA) axis function seem to have a significant role in the onset of anxiety. Existing data appear to support the mediating effect of the HPA axis between childhood traumata and posttraumatic stress disorder. Findings on the HPA axis activity at baseline and after stimuli in panic disordered patients are inconclusive, even if stressful life events may have a triggering function in the development of this disorder. Data on the relationship between stress, HPA axis functioning and obsessive-compulsive disorder (OCD) are scarce and discordant, but an increased activity of the HPA axis is reported in OCD patients. Moreover, normal basal cortisol levels and hyperresponsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. While several hypothesis have attempted to explain these findings over time, currently the most widely accepted theory is that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology. All theories are reviewed and the authors conclude that childhood life events and HPA abnormalities may be specifically and transnosographically related to all anxiety disorders, as well as, more broadly, to all psychiatric disorders.

Psychological vulnerability to stress in carriers of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

“…In patients with PD, both normal baseline activity and hyperresponsiveness of the HPA axis have been described. 13,32 SP is also associated with hyperresponsiveness of the HPA axis after exposure to psychosocial stressors. 32 On the other hand, patients with PTSD typically display a hypoactive HPA axis, although they have higher cerebrospinal fluid (CSF) CRH concentrations and smaller hippocampal volume than healthy controls.…”

“…13,32 SP is also associated with hyperresponsiveness of the HPA axis after exposure to psychosocial stressors. 32 On the other hand, patients with PTSD typically display a hypoactive HPA axis, although they have higher cerebrospinal fluid (CSF) CRH concentrations and smaller hippocampal volume than healthy controls. 13,32 The neuroendocrine alterations in PTSD have been attributed to a developmental programming secondary to early-life trauma.…”

“…32 On the other hand, patients with PTSD typically display a hypoactive HPA axis, although they have higher cerebrospinal fluid (CSF) CRH concentrations and smaller hippocampal volume than healthy controls. 13,32 The neuroendocrine alterations in PTSD have been attributed to a developmental programming secondary to early-life trauma. The latter may result in tissuespecific alterations in glucocorticoid sensitivity, enhanced negative feedback inhibition of the HPA axis, changes in glucocorticoid metabolism or low cortisol concentrations through epigenetic mechanisms.…”

“…33 Increased concentrations of CRH and AVP in plasma and CSF have been reported in patients with OCD, suggesting a hyperactive state of the HPA axis. 32 In GAD, data on HPA axis activity are inconsistent, 32,34 owing partly to the use of different diagnostic tools employed for the assessment of HPA axis function. Overall, it has been postulated that the persistent HPA axis hyperactivity observed in GAD may be mediated by changes in the sensitivity or in the number of CRH and/or glucocorticoid receptors in brain areas associated with anxiety disorders, including the amygdala, hippocampus and the prefrontal cortex.…”

“…Furthermore, an increased interaction between chronically elevated CRH and its type 1 receptor, altered receptor sensitivity or enhanced signaling capacity may result in higher state anxiety, possibly through transcriptional and/or epigenetic mechanisms. 14,32 In contrast, after prolonged periods of chronic stress an initially hyperactive HPA axis eventually evolves into a hypoactive state through down-regulation of CRH receptors in the pituitary, resulting in lower ACTH and cortisol secretion. 35,36 Hypoactivity of the HPA axis has been described in several physical and psychiatric disorders, including atypical depression, PTSD, chronic fatigue syndrome and fibromyalgia.…”