INFO_STRESS RESPONSIVITY_NEUROPHYSIO
How Stress Responsivity Works
The two main components of the human stress response are the sympathetic nervous system (SAM) and stress hormone production (via Hypothalamic Pituitary Adrenal Axis). Numerous areas of the brain can activate these systems (i.e. areas of the prefrontal cortex, hippocampus, amygdala, hypothalamic, and brain stem nuclei modulate both systems).
Corticotropin-releasing factor (CRF)–producing neurons oversee the entire mammalian stress response, coordinating the different organ systems of our body to handle a significant stressor. These CRF neurons are primarily located in the hypothalamus, which primarily regulates the HPA axis response to stress. But another important area that has to do with the fear response are CRF neurons in the amygdala are involved in processing emotional stress response. These neurons specifically send a signal to the only area of our brain that makes norepinephrine, which then in turn send signals to the sympathetic nervous system that ultimately stimulate release of epinephrine from the adrenal medulla.
CRF cells of the central nucleus of amygdala are involved in stress-induced activation of the HPA axis via an indirect pathway through the bed nucleus of the stria terminalis, where CRF neuronal projections innervate the PVN neurons of the hypothalamus. Following activation of the HPA axis, CRF is released from the PVN in to the adenohypophysial-portal circulation from nerve terminals in the median eminence where it stimulates adrenocorticotropin hormone (ACTH) release from the anterior pituitary.
ACTH in turn stimulates release of glucocorticoids (GCs) from the adrenal cortex . Able to permeate the blood-brain barrier, GCs reduce activation of the HPA axis via stimulation of GC receptors (GRs) within the hippocampus, hypothalamus, and anterior pituitary. The critical role of amygdalar CRF has brought to attention the widespread localization of CRF receptors throughout the CNS and their converging pathways in orchestrating stress.
The response to psychosocial stress, of which ELS represents a specific subtype, also involves “higher appraisal” by cortical and subcortical regions of brain containing CRFR1 receptors, namely, cingulate cortex, orbital/medial prefrontal cortex, and hippocampus ; all these areas comprise part of the converging pathways described above. Much evidence points to the role for CRF as a neurotransmitter coordinating immune, autonomic, endocrine, and behavioral stress responses, supported by the finding that CRFR1 receptors are more abundant in corticolimbic pathways that mediate fear- and anxiety-related behaviors. With this basic framework of stress response neurobiology, the concept of “stress responsivity” may be viewed through a model of posttraumatic stress disorder (PTSD).
While these systems tend to be dysfunctional in numerous psychiatric disorders, it is clearly those individuals diagnosed with PTSD show the most dysregulation of the stress response system. Criteria D for diagnosing PTSD in DSM5 requires that an individual demonstrates “marked alterations in arousal and reactivity associated with traumatic event(s)” in the form of hypervigilance, exaggerated startle response, increased irritability, problems with concentration, and/or sleep disturbance. The fact that many individuals with PTSD have experienced traumatic events that occurred in the form of child abuse and neglect comes as little surprise and further strengthens the argument for using PTSD-derived neurobiological research in developing the construct of “stress responsivity.”
Sympathetic Nervous System/Hypothalamic-pituitary-adrenal axis physiology
Sympathetic nervous system
The HPA axis represents the major neuroendocrine stress response system that serves to adapt the organism to change in life demands and thereby maintain homeostasis.
Perceived threat activates the sympathetic (SNS) and parasympathetic (PNS) nervous systems and recurrent high levels of threat exposure, particularly early in life, can significantly affect an individual's long-term ability to modulate the SNS and PNS response to future stressors . Although most of the scientific research has focused on the HPA axis, others have examined SNS reactivity.
Glucocorticoid feedback regulation of stress responsivity
Enhanced stress responsiveness after trauma might be further influenced by changes in GC-mediated feedback control of the HPA axis. In an initial study, we observed increased suppression of cortisol in a low-dose dexamethasone suppression test in abused women with depression and concurrent PTSD. Such hypersuppression indicates enhanced sensitivity of the pituitary to negative feedback and is a prominent finding in PTSD, believed to contribute to stress sensitization. In fact, the results found in this study might be best attributable to comorbidity with PTSD. We sought to determine the effects of childhood abuse on results in the dexamethasone/CRF test in adult men with and without current MDD. Abused men demonstrated markedly increased cortisol responses to dexamethasone/CRF administration when compared with nonabused men, regardless of diagnosis. When stratifying groups by MDD and childhood trauma, only those abused men with current MDD, but not depressed men without childhood trauma, demonstrated increased cortisol responses. Increased response was associated with exposure to both sexual and physical abuse and the severity of the abuse. Importantly, this effect was not attributable to comorbid PTSD. These results suggest that childhood trauma is associated with impaired GC-mediated feedback control of the HPA axis during stimulated conditions.