scholarly journals Sex-Dependent Association of DNA Methylation in the Coding Region of the Corticotropin-Releasing Hormone Gene and Schizophrenia

2021 ◽  
Author(s):  
Lili Qing ◽  
Peng Xiong ◽  
Yumei Lu ◽  
Hongyan Jiang ◽  
Shengjie Nie
Keyword(s):  
Hpa Axis ◽  
Peripheral Blood ◽  
Mental Disease ◽  
Methylation Status ◽  
Underlying Mechanism ◽  
Corticotropin Releasing Hormone ◽  
Coding Region ◽  
Releasing Hormone ◽  
Chronic Disability ◽  
Schizophrenic Patients

Abstract Schizophrenia (SCZ) is a common mental disease causing severe chronic disability. Epigenetic changes in HPA axis-related genes are considered to play an important role in SCZ pathogenesis. Unfortunately, the methylation status of the corticotropin-releasing hormone ( CRH ) gene, which is the central driving force in the HPA axis, has not been reported in SCZ patients. Here, we used the sodium bisulfite and MethylTarget methods to detect the DNA methylation status of the CRH gene coding region in peripheral blood samples from 70 schizophrenic patients and 68 healthy controls. The results showed that the methylation level of the CRH gene CDS was significantly increased in SCZ patients, especially in the male subgroup. In conclusion, this study showed that differences in CRH gene CDS methylation were detectable in the peripheral blood of SCZ patients and that epigenetic abnormalities in the CRH gene were closely related to SCZ, revealing that epigenetic processes may mediate the pathophysiology of SCZ. Further research should address the underlying mechanism whereby CRH gene methylation regulates the occurrence and development of SCZ.

Consistent Reduction of ACTH responses to stimulation with CRH, Vasopressin and Hypoglycaemia in Patients with Major Depression

1989 ◽  
Vol 155 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Roger G. Kathol ◽  
Richard S. Jaeckle ◽  
Juan F. Lopez ◽  
William H. Meller
Keyword(s):  
Major Depression ◽  
Hpa Axis ◽  
Negative Correlation ◽  
Arginine Vasopressin ◽  
Corticotropin Releasing Hormone ◽  
Hypothalamic Pituitary Adrenal ◽  
Releasing Hormone ◽  
Control Subjects ◽  
Basal Cortisol ◽  
Cortisol Responses

Eleven patients with major depression and 12 control subjects were administered corticotropin-releasing hormone (CRH), aqueous arginine vasopressin (AVP), and insulin hypoglycaemia (IH) to test for differences in hypothalamic–pituitary–adrenal (HPA) axis function. Patients with major depression demonstrated lower ACTH responses to CRH when compared with controls, and a trend toward such after administration of AVP. Despite lower ACTH responses in patients with depression, there were no differences in Cortisol responses to these stimuli. In the CRH and AVP tests, there was no correlation between the basal Cortisol and ACTH responses in either controls or patients, but in the IH test there was a negative correlation between these responses for both groups. The ACTH responses to CRH and AVP were positively correlated in controls and patients. Cortisol responses to all three provocative stimuli were positively correlated in both subject groups. These findings are consistent with the hypothesis that hypothalamic or supra-hypothalamic overactivity may be involved in the development of HPA-axis abnormalities in patients with depression.

THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS OF PATIENTS WITH SEVERE SEPSIS: ALTERED RESPONSE TO CORTICOTROPIN-RELEASING HORMONE (CRH)

1999 ◽  
Vol 27 (Supplement) ◽  
pp. A144
Author(s):  
Stefan Schroeder ◽  
Maria Wichers ◽  
Lutz E Lehmann ◽  
Christian Putensen ◽  
Andreas Hoeft ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Hpa Axis ◽  
Corticotropin Releasing Hormone ◽  
Hypothalamic Pituitary Adrenal ◽  
Releasing Hormone ◽  
Altered Response

Abstract 340: Psychological Stress Impairs Both Endothelial Function and Insulin Sensitivity via Activation of Inflammation and ER Stress Pathways Mediated by Corticotropin-Releasing Hormone

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Ick-Mo Chung ◽  
Hee Young Kim ◽  
Youn Jung Lee
Keyword(s):  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Er Stress ◽  
Psychological Stress ◽  
Underlying Mechanism ◽  
Control Group ◽  
No Production ◽  
Nuclear Fraction ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone

Background: Psychological stress may contribute to atherogenesis, although the underlying mechanism is poorly understood yet. We studied the role of corticotropin-releasing hormone (CRH) in the pathogenesis of stress-induced endothelial dysfunction and insulin resistance with specific focus on inflammation and ER stress pathways. Methods and Results: Immobilization stress (IS) was applied (2 hr/d) for 14 d to male 8-wk OLETF rats, whereas control groups comprised of rats without IS (n≥7 for each). 14d-IS decreased acetylcholine (Ach)-induced NO production, measured by direct NO electrochemical microsensor, from the aorta along with decreased expression of eNOS mRNA compared with control group. 14d-IS did not significantly change plasma glucose, but increased plasma insulin (342.5±6.3 vs. 496.0±51.6 pg/ml, p<0.05) and HOMA-IR (3.1±0.2 vs.4.7±0.5 mmol/LxμIU/mL, p<0.05) compared with control group. IS increased phosphorylation of both IRS1 serine and ERK, and increased expression of ER stress marker BiP. IS also increased translocation of NF-kB subunit p65 into nucleal fraction, and increased mRNA expression of both TNF-α and MCP-1 in the liver. Real-time RT-qPCR study showed that 1d IS increased expression of CRH mRNA and urocortin 2 mRNA in the hypothalamus by 2.5 folds and expression of CRH receptor type 2 mRNA in the aorta by 7.8 folds compared with control group. In cultured monocyte U937 cells, CRH induced translocation of NF-kB subunit p65 into nuclear fraction, and increased expression of BiP, phosphorylated inositol requiring enzyme 1, and MCP-1 mRNA. In cultured HUVECs, CRH pretreatment inhibited insulin-stimulated eNOS phosphorylation at Ser 1177 . Conclusions: Psychological stress impairs both endothelial function and insulin sensitivity probably via activation of NF-kB-mediated inflammation and ER stress pathways by CRH.

scholarly journals Modulation of Sleep Homeostasis by Corticotropin Releasing Hormone in REM Sleep-Deprived Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Ricardo Borges Machado ◽  
Sergio Tufik ◽  
Deborah Suchecki
Keyword(s):  
Sleep Deprivation ◽  
Hpa Axis ◽  
Rem Sleep ◽  
Rapid Eye Movement Sleep ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Sleep Homeostasis ◽  
Impaired Sleep ◽  
Hypothalamic Level ◽  
Pituitary Adrenal Axis

Studies have shown that sleep recovery following different protocols of forced waking varies according to the level of stress inherent to each method. Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and increased corticotropin-releasing hormone (CRH) impairs sleep. The purpose of the present study was to evaluate how manipulations of the CRH system during the sleep deprivation period interferes with subsequent sleep rebound. Throughout 96 hours of sleep deprivation, separate groups of rats were treated i.c.v. with vehicle, CRH or with alphahelical , a CRH receptor blocker, twice/day, at 07:00 h and 19:00 h. Both treatments impaired sleep homeostasis, especially in regards to length of rapid eye movement sleep (REM) and theta/delta ratio and induced a later decrease in NREM and REM sleep and increased waking bouts. These changes suggest that activation of the CRH system impact negatively on the homeostatic sleep response to prolonged forced waking. These results indicate that indeed, activation of the HPA axis—at least at the hypothalamic level—is capable to reduce the sleep rebound induced by sleep deprivation.

scholarly journals Effects of sex and early maternal abuse on adrenocorticotropin hormone and cortisol responses to the corticotropin-releasing hormone challenge during the first 3 years of life in group-living rhesus monkeys

2010 ◽  
Vol 22 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Mar M. Sanchez ◽  
Kai Mccormack ◽  
Alison P. Grand ◽  
Richelle Fulks ◽  
Anne Graff ◽  
...  
Keyword(s):  
Sex Differences ◽  
Hpa Axis ◽  
Rhesus Monkeys ◽  
Group Living ◽  
Cortisol Response ◽  
Corticotropin Releasing Hormone ◽  
Long Term Effects ◽  
Releasing Hormone ◽  
Cortisol Responses

AbstractIn this study we investigated the development of the hypothalamic–pituitary–adrenal (HPA) axis in 21 group-living rhesus monkeys infants that were physically abused by their mothers in the first few months of life and in 21 nonabused controls. Cortisol and adrenocorticotropin hormone (ACTH) responses to a corticotropin-releasing hormone (CRH) challenge were assessed at 6-month intervals during the subjects' first 3 years of life. Abused infants exhibited greater cortisol responses to CRH than controls across the 3 years. Abused infants also exhibited blunted ACTH secretion in response to CRH, especially at 6 months of age. Although there were no significant sex differences in abuse experienced early in life, females showed a greater cortisol response to CRH than males at all ages. There were no significant sex differences in the ACTH response to CRH, or significant interactions between sex and abuse in the ACTH or cortisol response. Our findings suggest that early parental maltreatment results in greater adrenocortical, and possibly also pituitary, responsiveness to challenges later in life. These long-term alterations in neuroendocrine function may be one the mechanisms through which infant abuse results in later psychopathologies. Our study also suggests that there are developmental sex differences in adrenal function that occur irrespective of early stressful experience. The results of this study can enhance our understanding of the long-term effects of child maltreatment as well as our knowledge of the development of the HPA axis in human and nonhuman primates.

HPA axis dysregulation in mice overexpressing corticotropin releasing hormone

2002 ◽  
Vol 51 (11) ◽  
pp. 875-881 ◽  
Author(s):  
Lucianne Groenink ◽  
Anneloes Dirks ◽  
P.Monika Verdouw ◽  
Marlies lutje Schipholt ◽  
Jan G Veening ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Hpa Axis Dysregulation

Altered adrenocorticotropin and cortisol response to corticotropin-releasing hormone in HIV-1 infection

1995 ◽  
Vol 133 (2) ◽  
pp. 173-179 ◽  
Author(s):  
Alberto Biglino ◽  
Paolo Limone ◽  
Brunella Forno ◽  
Annamaria Pollono ◽  
Giuseppe Cariti ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Hpa Axis ◽  
Stage Iv ◽  
Cortisol Response ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Positive Linear Correlation ◽  
Healthy Control ◽  
Cortisol Responses ◽  
Adrenal Response

Biglino A, Limone P, Forno B, Pollono A, Cariti G, Molinatti GM, Gioannini P. Altered adrenocorticotropin and cortisol response to corticotropin-releasing hormone in HIV-I infection. Eur J Endocrinol 1995;133:173-9. ISSN 0804-4643 Alterations of the hypothalamic-pituitary-adrenal (HPA) axis are common in HIV infection. To characterize further the site of these derangements and their possible causes, eight male drug addicts with symptomatic HIV infection (stage IV C2) underwent the following investigations: repeated baseline determinations of cortisol, adrenocorticotropin (ACTH), interleukin 1β (IL-1β), IL-6 and interferon alpha (IFN-α): and ovine corticotropin-releasing hormone (CRH) test (100 μg IV) for ACTH and cortisol determinations. Baseline cortisol levels were either normal or elevated in all patients. A significant positive linear correlation was found between baseline levels of cortisol and both IL-6 (r=0.955; p<0.001) and IL-1β (r=0.863; p<0.005), but not between cortisol and ACTH or between ACTH and circulating cytokines. Both ACTH and cortisol responses to CRH were nearly absent in six out of eight patients, and delayed in the others. The areas under the curves of both ACTH and cortisol after CRH were significantly lower in HIV patients than in a group of eight healthy control subjects (p=0.0157 for ACTH and p=0.046 for cortisol). Our data suggest the possibility of an inappropriate stimulation of the HPA axis in symptomatic HIV infection by HIV-induced release of cytokines, with a blunted pituitary and adrenal response to CRH. Paolo Limone, Institute of Internal Medicine, University of Torino, C.so AM Dogliotti 14, 10126 Torino, Italy

Hypothalamo-pituitary-adrenal axis abnormalities in depression: a review and a model

1989 ◽  
Vol 19 (2) ◽  
pp. 331-336 ◽  
Author(s):  
Bruce G. Charlton ◽  
I. Nicol Ferrier
Keyword(s):  
Hpa Axis ◽  
Future Experiment ◽  
Hormone Regulation ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Adrenal Axis ◽  
Recent Advances ◽  
Wide Range ◽  
Pituitary Adrenal Axis

SynopsisA wide range of abnormalities of the hypothalamo-pituitary-adrenal (HPA) axis has been described in depression. This paper reviews recent advances in the understanding of this system, and draws them together to construct a model for the purposes of further research and discussion. It is proposed that there are two fundamental changes which both originate in the hypothalamus: an increased secretion of corticotropin-releasing hormone, and a neurally mediated adrenal hyper-responsivity to ACTH. The resulting changes in hormone regulation would be expected to produce all the characteristic HPA axis abnormalities commonly seen in depression. The model makes several predictions which could be tested by future experiment.

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