Psychoneuroendocrine assessment of posttraumatic stress disorder: Current progress and new directions

Altered locus coeruleus–norepinephrine function following single prolonged stress

“…Furthermore, SPS is one of only two models of PTSD (SPS and predator exposure) (Kozlovsky et al ., ) that reproduce the signature neuroendocrine abnormality associated with PTSD of enhanced glucocorticoid negative feedback (Pitman et al ., ). This is consistent with the glucocorticoid hypersensitivity found in PTSD patients (Yehuda et al ., ). Critically, glucocorticoid receptor (GR) upregulation is observed in SPS only after the 7‐day quiescent period has elapsed (Liberzon et al ., , ), and our laboratory has recently demonstrated that this upregulation is necessary for the expression of SPS‐specific extinction retention deficits (Knox et al ., ,b), which, in turn, are critical to PTSD symptomology (Milad et al ., ).…”

Altered locus coeruleus–norepinephrine function following single prolonged stress

“…Furthermore, SPS is one of only two models of PTSD (SPS and predator exposure) (Kozlovsky et al ., ) that reproduce the signature neuroendocrine abnormality associated with PTSD of enhanced glucocorticoid negative feedback (Pitman et al ., ). This is consistent with the glucocorticoid hypersensitivity found in PTSD patients (Yehuda et al ., ). Critically, glucocorticoid receptor (GR) upregulation is observed in SPS only after the 7‐day quiescent period has elapsed (Liberzon et al ., , ), and our laboratory has recently demonstrated that this upregulation is necessary for the expression of SPS‐specific extinction retention deficits (Knox et al ., ,b), which, in turn, are critical to PTSD symptomology (Milad et al ., ).…”

Relevance of Neuroendocrine Alterations in PTSD to Memory-Related Impairments of Trauma Survivors

“…The enhanced negative feedback model suggests that the primary deficit in PTSD is an increased responsiveness of glucocorticoid receptors at several sites along the hypothalamic-pituitary-adrenal axis (Yehuda, Giller, Southwick & Siever, 1995c;Yehuda, Giller & Mason, 1993c). The enhanced receptor responsiveness results in a stronger negative feedback and attenuated basal cortisol levels and enhanced responsiveness to exogenous steroid (i.e., dexamethasone).…”

Exposure to war and conflict: The individual and inherited epigenetic effects on health, with a focus on post-traumatic stress disorder

“…The current global issues, including the war in Ukraine, civil unrest in Iran, upheaval in Afghanistan, conflict in Ethiopia, South Sudan, and Syria (and undoubtably numerous more yet less widely publicised unrest), result in a drive to take in refugees. One review has noted primary healthcare as the prevalent support type used by refugees (98.7%) and found to be the most useful (27.5%) (16). This highlights the necessity to understand epigenetic impacts that may further contribute to, or drive, psychological and/or physiological complications to improve support for vulnerable populations.…”

“…Hypothalamic–pituitary–adrenal (HPA) axis dysfunction is one of the aetiological factors linked with PTSD ( 17 , 18 ). The GR, responding to cortisol, is a key player in this axis ( 19 ).…”

“…Increases in cortisol are often associated with higher levels of stress. Paradoxically, patients with chronic PTSD may exhibit lower cortisol, and lowered urinary cortisol after a traumatic event may be predictive of PTSD development ( 18 , 20 ). It is important to note that cortisol levels are not pathologically low, and still follow a circadian rhythm, but are significantly lower compared to individuals without PTSD ( 18 , 21 ).…”

Altered locus coeruleus–norepinephrine function following single prolonged stress

“…Furthermore, SPS is one of only two models of PTSD (SPS and predator exposure) (Kozlovsky et al ., ) that reproduce the signature neuroendocrine abnormality associated with PTSD of enhanced glucocorticoid negative feedback (Pitman et al ., ). This is consistent with the glucocorticoid hypersensitivity found in PTSD patients (Yehuda et al ., ). Critically, glucocorticoid receptor (GR) upregulation is observed in SPS only after the 7‐day quiescent period has elapsed (Liberzon et al ., , ), and our laboratory has recently demonstrated that this upregulation is necessary for the expression of SPS‐specific extinction retention deficits (Knox et al ., ,b), which, in turn, are critical to PTSD symptomology (Milad et al ., ).…”

Relevance of Neuroendocrine Alterations in PTSD to Memory-Related Impairments of Trauma Survivors

“…The enhanced negative feedback model suggests that the primary deficit in PTSD is an increased responsiveness of glucocorticoid receptors at several sites along the hypothalamic-pituitary-adrenal axis (Yehuda, Giller, Southwick & Siever, 1995c;Yehuda, Giller & Mason, 1993c). The enhanced receptor responsiveness results in a stronger negative feedback and attenuated basal cortisol levels and enhanced responsiveness to exogenous steroid (i.e., dexamethasone).…”

Exposure to war and conflict: The individual and inherited epigenetic effects on health, with a focus on post-traumatic stress disorder

“…The current global issues, including the war in Ukraine, civil unrest in Iran, upheaval in Afghanistan, conflict in Ethiopia, South Sudan, and Syria (and undoubtably numerous more yet less widely publicised unrest), result in a drive to take in refugees. One review has noted primary healthcare as the prevalent support type used by refugees (98.7%) and found to be the most useful (27.5%) (16). This highlights the necessity to understand epigenetic impacts that may further contribute to, or drive, psychological and/or physiological complications to improve support for vulnerable populations.…”

“…Hypothalamic–pituitary–adrenal (HPA) axis dysfunction is one of the aetiological factors linked with PTSD ( 17 , 18 ). The GR, responding to cortisol, is a key player in this axis ( 19 ).…”

“…Increases in cortisol are often associated with higher levels of stress. Paradoxically, patients with chronic PTSD may exhibit lower cortisol, and lowered urinary cortisol after a traumatic event may be predictive of PTSD development ( 18 , 20 ). It is important to note that cortisol levels are not pathologically low, and still follow a circadian rhythm, but are significantly lower compared to individuals without PTSD ( 18 , 21 ).…”

Altered locus coeruleus–norepinephrine function following single prolonged stress

“…Furthermore, SPS is one of only two models of PTSD (SPS and predator exposure) (Kozlovsky et al ., ) that reproduce the signature neuroendocrine abnormality associated with PTSD of enhanced glucocorticoid negative feedback (Pitman et al ., ). This is consistent with the glucocorticoid hypersensitivity found in PTSD patients (Yehuda et al ., ). Critically, glucocorticoid receptor (GR) upregulation is observed in SPS only after the 7‐day quiescent period has elapsed (Liberzon et al ., , ), and our laboratory has recently demonstrated that this upregulation is necessary for the expression of SPS‐specific extinction retention deficits (Knox et al ., ,b), which, in turn, are critical to PTSD symptomology (Milad et al ., ).…”

Relevance of Neuroendocrine Alterations in PTSD to Memory-Related Impairments of Trauma Survivors

“…The enhanced negative feedback model suggests that the primary deficit in PTSD is an increased responsiveness of glucocorticoid receptors at several sites along the hypothalamic-pituitary-adrenal axis (Yehuda, Giller, Southwick & Siever, 1995c;Yehuda, Giller & Mason, 1993c). The enhanced receptor responsiveness results in a stronger negative feedback and attenuated basal cortisol levels and enhanced responsiveness to exogenous steroid (i.e., dexamethasone).…”

Exposure to war and conflict: The individual and inherited epigenetic effects on health, with a focus on post-traumatic stress disorder

“…The current global issues, including the war in Ukraine, civil unrest in Iran, upheaval in Afghanistan, conflict in Ethiopia, South Sudan, and Syria (and undoubtably numerous more yet less widely publicised unrest), result in a drive to take in refugees. One review has noted primary healthcare as the prevalent support type used by refugees (98.7%) and found to be the most useful (27.5%) (16). This highlights the necessity to understand epigenetic impacts that may further contribute to, or drive, psychological and/or physiological complications to improve support for vulnerable populations.…”

“…Hypothalamic–pituitary–adrenal (HPA) axis dysfunction is one of the aetiological factors linked with PTSD ( 17 , 18 ). The GR, responding to cortisol, is a key player in this axis ( 19 ).…”

“…Increases in cortisol are often associated with higher levels of stress. Paradoxically, patients with chronic PTSD may exhibit lower cortisol, and lowered urinary cortisol after a traumatic event may be predictive of PTSD development ( 18 , 20 ). It is important to note that cortisol levels are not pathologically low, and still follow a circadian rhythm, but are significantly lower compared to individuals without PTSD ( 18 , 21 ).…”