When not enough is too much : the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders
OBJECTIVE: Previous theories have emphasized the role of excessive glucocorticoid activity in the pathology of chronic stress. Nevertheless, insufficient glucocorticoid signaling (resulting from decreased hormone bioavailability or reduced hormone sensitivity) may have equally devastating effects on bodily function. Such effects may be related in part to the role of glucocorticoids in restraining activation of the immune system and other components of the stress response, including the sympathetic nervous system (SNS) and corticotropin-releasing hormone (CRH).
METHOD: The literature on neuroendocrine function and glucocorticoid-relevant pathologies in stress-related neuropsychiatric disorders, including posttraumatic stress disorder and major depression, was reviewed.
RESULTS: Although not occurring together, both hypocortisolism and reduced responsiveness to glucocorticoids (as determined by dexamethasone challenge tests) were reliably found. Stress-related neuropsychiatric disorders were also associated with immune system activation/inflammation, high SNS tone, and CRH hypersecretion, which are all consistent with insufficient glucocorticoid-mediated regulation of stress hyperresponsiveness. Finally, antidepressants, a mainstay in the treatment of stress-related disorders, were regularly associated with evidence of enhanced glucocorticoid signaling.
CONCLUSIONS: Neuroendocrine data provide evidence of insufficient glucocorticoid signaling in stress-related neuropsychiatric disorders. Impaired feedback regulation of relevant stress responses, especially immune activation/inflammation, may, in turn, contribute to stress-related pathology, including alterations in behavior, insulin sensitivity, bone metabolism, and acquired immune responses. From an evolutionary perspective, reduced glucocorticoid signaling, whether achieved at the level of the hormone or its receptor, may foster immune readiness and increase arousal. Emphasis on insufficient glucocorticoid signaling in stress-related pathology encourages development of therapeutic strategies to enhance glucocorticoid signaling pathways.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2003 |
|---|---|
| Erschienen: |
2003 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:160 |
|---|---|
| Enthalten in: |
The American journal of psychiatry - 160(2003), 9 vom: 16. Sept., Seite 1554-65 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Raison, Charles L [VerfasserIn] |
|---|
| Anmerkungen: |
Date Completed 18.12.2003 Date Revised 30.03.2022 published: Print Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM126941122 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM126941122 | ||
| 003 | DE-627 | ||
| 005 | 20231222212922.0 | ||
| 007 | tu | ||
| 008 | 231222s2003 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0423.xml |
| 035 | |a (DE-627)NLM126941122 | ||
| 035 | |a (NLM)12944327 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Raison, Charles L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a When not enough is too much |b the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders |
| 264 | 1 | |c 2003 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 18.12.2003 | ||
| 500 | |a Date Revised 30.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: Previous theories have emphasized the role of excessive glucocorticoid activity in the pathology of chronic stress. Nevertheless, insufficient glucocorticoid signaling (resulting from decreased hormone bioavailability or reduced hormone sensitivity) may have equally devastating effects on bodily function. Such effects may be related in part to the role of glucocorticoids in restraining activation of the immune system and other components of the stress response, including the sympathetic nervous system (SNS) and corticotropin-releasing hormone (CRH) | ||
| 520 | |a METHOD: The literature on neuroendocrine function and glucocorticoid-relevant pathologies in stress-related neuropsychiatric disorders, including posttraumatic stress disorder and major depression, was reviewed | ||
| 520 | |a RESULTS: Although not occurring together, both hypocortisolism and reduced responsiveness to glucocorticoids (as determined by dexamethasone challenge tests) were reliably found. Stress-related neuropsychiatric disorders were also associated with immune system activation/inflammation, high SNS tone, and CRH hypersecretion, which are all consistent with insufficient glucocorticoid-mediated regulation of stress hyperresponsiveness. Finally, antidepressants, a mainstay in the treatment of stress-related disorders, were regularly associated with evidence of enhanced glucocorticoid signaling | ||
| 520 | |a CONCLUSIONS: Neuroendocrine data provide evidence of insufficient glucocorticoid signaling in stress-related neuropsychiatric disorders. Impaired feedback regulation of relevant stress responses, especially immune activation/inflammation, may, in turn, contribute to stress-related pathology, including alterations in behavior, insulin sensitivity, bone metabolism, and acquired immune responses. From an evolutionary perspective, reduced glucocorticoid signaling, whether achieved at the level of the hormone or its receptor, may foster immune readiness and increase arousal. Emphasis on insufficient glucocorticoid signaling in stress-related pathology encourages development of therapeutic strategies to enhance glucocorticoid signaling pathways | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 4 | |a Review | |
| 650 | 7 | |a Glucocorticoids |2 NLM | |
| 650 | 7 | |a Receptors, Glucocorticoid |2 NLM | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 650 | 7 | |a Adrenocorticotropic Hormone |2 NLM | |
| 650 | 7 | |a 9002-60-2 |2 NLM | |
| 650 | 7 | |a Corticotropin-Releasing Hormone |2 NLM | |
| 650 | 7 | |a 9015-71-8 |2 NLM | |
| 650 | 7 | |a Hydrocortisone |2 NLM | |
| 650 | 7 | |a WI4X0X7BPJ |2 NLM | |
| 700 | 1 | |a Miller, Andrew H |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The American journal of psychiatry |d 1945 |g 160(2003), 9 vom: 16. Sept., Seite 1554-65 |w (DE-627)NLM000012440 |x 1535-7228 |7 nnns |
| 773 | 1 | 8 | |g volume:160 |g year:2003 |g number:9 |g day:16 |g month:09 |g pages:1554-65 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 160 |j 2003 |e 9 |b 16 |c 09 |h 1554-65 | ||