Salivary Cortisol and Psychopathology in Adults Bereaved by the September 11, 2001 Terror Attacks

Objective: This prospective study aimed to describe the nature and time course of HPA axis dysregulation and psychopathology among terror-bereaved spouses. Method: Twenty-three spouses bereaved from September 11, 2001 terror attacks and 22 nonbereaved spouses were compared using a psychiatric diagnostic interview (SCID), 3 days of salivary cortisol collection, and a dexamethasone suppression test. Most subjects had repeated assessments at 6 month intervals during the 2 year study. Results: After September 11, 2001, bereaved compared to nonbereaved had significantly higher rates of posttraumatic stress disorder (PTSD; 68.1% versus 0%) and major depressive disorder (MDD; 45.5% versus 9.5%). Bereaved had significantly higher morning basal cortisol and less afternoon postdexamethasone cortisol suppression than nonbereaved. Among bereaved, those with PTSD without comorbid MDD had significantly greater afternoon postdexamethasone cortisol suppression than those without psychiatric disorders. Conclusions: Terror-related spouse death is a severe stressor associated with persistent HPA axis activation, PTSD, and MDD. However, bereaved spouses who developed PTSD and were not depressed had enhanced post-dexamethasone cortisol suppression, evidence of heightened glucocorticoid receptor sensitivity.

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Childhood traumata, Dexamethasone Suppression Test and psychiatric symptoms: a trans-diagnostic approach

Psychological Medicine ◽

10.1017/s0033291710000115 ◽

2010 ◽

Vol 40 (12) ◽

pp. 2037-2048 ◽

Cited By ~ 19

Author(s):

C. Faravelli ◽

S. Gorini Amedei ◽

F. Rotella ◽

L. Faravelli ◽

A. Palla ◽

...

Keyword(s):

Life Events ◽

Hpa Axis ◽

Salivary Cortisol ◽

Psychiatric Symptoms ◽

Dexamethasone Suppression Test ◽

Diagnostic Approach ◽

Stressful Event ◽

Suppression Test ◽

Hpa Response ◽

Dexamethasone Suppression

BackgroundChildhood traumatic events and functional abnormalities of the hypothalamus–pituitary–adrenal (HPA) axis have been widely reported in psychiatric patients, although neither is specific for any diagnosis. Among the limited number of studies that have evaluated these topics, none has adopted a trans-diagnostic approach. The aim of the present research is to explore the relationship between childhood stressors, HPA axis function and psychiatric symptoms, independent of the diagnosis.MethodA total of 93 moderate to severely ill psychiatric out-patients of Florence and Pisa University Psychiatric Units and 33 healthy control subjects were recruited. The assessment consisted of salivary cortisol pre- and post-low dose (0.5 mg) Dexamethasone, early and recent life events, 121 psychiatric symptoms independent of diagnosis, SCID, BPRS.ResultsIn total, 33.5% of patients were Dexamethasone Suppression Test (DST) non-suppressors, compared with 6.1% of controls (p=0.001). Among patients, non-suppression was associated with particular symptoms (i.e. depressive and psychotic), but not to any specific diagnosis. Early stressful life events were significantly associated with higher salivary cortisol levels, with DST non-suppression and with approximately the same subset of symptoms. A recent stressful event seemed to be associated to the HPA response only in those subjects who were exposed to early traumata.ConclusionsOur report suggests a relationship between life stress, HPA axis and psychopathology. A cluster of specific psychiatric symptoms seems to be stress related. Moreover, it seems that an abnormal HPA response is possibly triggered by an excessive pressure in vulnerable individuals.

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Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder

The British Journal of Psychiatry ◽

10.1192/bjp.184.6.496 ◽

2004 ◽

Vol 184 (6) ◽

pp. 496-502 ◽

Cited By ~ 227

Author(s):

Stuart Watson ◽

Peter Gallagher ◽

James C. Ritchie ◽

I. Nicol Ferrier ◽

Allan H. Young

Keyword(s):

Bipolar Disorder ◽

Hpa Axis ◽

Cortisol Response ◽

Hypothalamic Pituitary Adrenal ◽

The Core ◽

Basal Cortisol ◽

Suppression Test ◽

Cortisol Levels ◽

Dexamethasone Suppression ◽

Pituitary Adrenal Axis

BackgroundHypothalamic-pituitary-adrenal (HPA) axis function, as variously measured by the responses to the combined dexamethasone/ corticotrophin-releasing hormone (dex/ CRH) test, the dexamethasone suppression test (DST) and basal cortisol levels, has been reported to be abnormal in bipolar disorder.AimsTo test the hypothesis that HPA axis dysfunction persists in patients in remission from bipolar disorder.MethodSalivary cortisol levels and the plasma cortisol response to the DST and dex/CRH test were examined in 53 patients with bipolar disorder, 27 of whom fulfilled stringent criteria for remission, and in 28 healthy controls. Serum dexamethasone levels were measured.ResultsPatients with bipolar disorder demonstrated an enhanced cortisol response to the dex/CRH test compared with controls (P=0.001). This response did not differ significantly between remitted and non-remitted patients. These findings were present after the potentially confounding effects of dexamethasone levels were accounted for.ConclusionsThe dex/CRH test is abnormal in both remitted and non-remitted patients with bipolar disorder. Thismeasure of HP Aaxis dysfunction is a potential trait marker in bipolar disorder and thus possibly indicative of the core pathophysiological process in this illness.

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Salivary Cortisol and Psychopathology in Children Bereaved by the September 11, 2001 Terror Attacks

Biological Psychiatry ◽

10.1016/j.biopsych.2006.07.037 ◽

2007 ◽

Vol 61 (8) ◽

pp. 957-965 ◽

Cited By ~ 82

Author(s):

Cynthia R. Pfeffer ◽

Margaret Altemus ◽

Moonseong Heo ◽

Hong Jiang

Keyword(s):

Salivary Cortisol ◽

September 11 ◽

Terror Attacks

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Childhood Maltreatment and Its Interaction with Hypothalamic–Pituitary–Adrenal Axis Activity and the Remission Status of Major Depression: Effects on Functionality and Quality of Life

Brain Sciences ◽

10.3390/brainsci11040495 ◽

2021 ◽

Vol 11 (4) ◽

pp. 495

Author(s):

Neus Salvat-Pujol ◽

Javier Labad ◽

Mikel Urretavizcaya ◽

Aida De Arriba-Arnau ◽

Cinto Segalàs ◽

...

Keyword(s):

Quality Of Life ◽

Depressive Symptoms ◽

Hpa Axis ◽

Childhood Maltreatment ◽

Hypothalamic Pituitary Adrenal ◽

Remission Status ◽

Suppression Test ◽

Cortisol Suppression ◽

Dexamethasone Suppression

Relationships among childhood maltreatment (CM), hypothalamic-pituitary-adrenal (HPA) axis disturbances, major depressive disorder (MDD), poor functionality, and lower quality of life (QoL) in adulthood have been described. We aimed to study the roles of the remission status of depression and HPA axis function in the relationships between CM and functionality and QoL. Ninety-seven patients with MDD and 97 healthy controls were included. The cortisol awakening response, cortisol suppression ratio in the dexamethasone suppression test, and diurnal cortisol slope were assessed. Participants completed measures of psychopathology, CM, functionality, and QoL. Multiple linear regression analyses were performed to study the relationships between CM and functionality and QoL. Only non-remitted MDD patients showed lower functionality and QoL than controls, indicating that depressive symptoms may partly predict functionality and QoL. Cortisol measures did not differ between remitted and non-remitted patients. Although neither HPA axis measures nor depression remission status were consistently associated with functionality or QoL, these factors moderated the effects of CM on functionality and QoL. In conclusion, subtle neurobiological dysfunctions in stress-related systems could help to explain diminished functionality and QoL in individuals with CM and MDD and contribute to the persistence of these impairments even after the remission of depressive symptoms.

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The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD

International Journal of Molecular Sciences ◽

10.3390/ijms22115495 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5495

Author(s):

Felipe Borges Almeida ◽

Graziano Pinna ◽

Helena Maria Tannhauser Barros

Keyword(s):

Hpa Axis ◽

Depressive Disorders ◽

Post Traumatic Stress ◽

Major Depressive ◽

Physiological Adaptations ◽

Suppression Test ◽

Post Traumatic ◽

Major Depressive Disorders ◽

Cortisol Release

Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.

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Adverse childhood experiences, daytime salivary cortisol, and depressive symptoms in early adulthood: a longitudinal genetically informed twin study

Translational Psychiatry ◽

10.1038/s41398-021-01538-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eleonora Iob ◽

Jessie R. Baldwin ◽

Robert Plomin ◽

Andrew Steptoe

Keyword(s):

Depressive Symptoms ◽

Hpa Axis ◽

Salivary Cortisol ◽

Adverse Childhood Experiences ◽

Emotional Abuse ◽

Early Adulthood ◽

Cumulative Exposure ◽

Childhood Experiences ◽

Adverse Childhood ◽

Cortisol Levels

AbstractDysregulated hypothalamic–pituitary–adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3–11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = −0.20, p = 0.03), bullying (b = −0.61, p = 0.01), and emotional abuse (b = −0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = −0.56, p = 0.05). Lower cortisol levels mediated around 10–20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02–0.34]) and bullying (b = 0.18 [0.01–0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.

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Neuroendocrine Assessment of Dopaminergic Function during Antidepressant Treatment in Major Depressed Patients

Brain Sciences ◽

10.3390/brainsci11040425 ◽

2021 ◽

Vol 11 (4) ◽

pp. 425

Author(s):

Fabrice Duval ◽

Marie-Claude Mokrani ◽

Alexis Erb ◽

Felix Gonzalez Lopera ◽

Vlad Danila ◽

...

Keyword(s):

Hpa Axis ◽

Antidepressant Treatment ◽

Cortisol Response ◽

Mesolimbic Pathway ◽

Suppression Test ◽

Pre Treatment ◽

Hpa Axis Activity ◽

Drug Free ◽

Hypothalamic Level ◽

Dexamethasone Suppression

The effects of antidepressants on dopamine (DA) receptor sensitivity in the mesolimbic–hypothalamic system have yielded contradictory results. The postsynaptic DA receptor function was evaluated by the cortisol response to apomorphine (APO; 0.75 mg SC) in 16 drug-free DSM-5 major depressed inpatients and 18 healthy hospitalized control (HC) subjects. Cortisol response to the dexamethasone suppression test (DST) was also measured. After two and four weeks of antidepressant treatment (ADT), the DST and APO test were repeated in all patients. Cortisol response to APO (∆COR) was not influenced by the hypothalamic–pituitary–adrenal (HPA) axis activity, as assessed by the DST. Pre-treatment ∆COR values did not differ significantly between patients and HCs. During ADT, ∆COR values were lower than in HCs at week 2 and 4. After four weeks of treatment, among the eight patients who had blunted ∆COR values, seven were subsequent remitters, while among the eight patients who had normal ∆COR values, seven were non-remitters. Considering the limitations of our study, the results suggest that following chronic ADT, the desensitization of postsynaptic DA receptors connected with the regulation of the HPA axis at the hypothalamic level is associated with clinical remission. These results could reflect increased DA levels in the mesolimbic pathway.

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Abstract 293: Cardiac Arrest and Resuscitation Causes Immunodeficiency That Involves the Hypothalamic-Pituitary-Adrenal Axis

Circulation ◽

10.1161/circ.138.suppl_2.293 ◽

2018 ◽

Vol 138 (Suppl_2) ◽

Author(s):

Yuntian Shen ◽

Qiang Zhao ◽

Jiangbo Wu ◽

Zhuoran Wang ◽

Wei Yang

Keyword(s):

Immune Response ◽

Cardiac Arrest ◽

Immune System ◽

Hpa Axis ◽

Time Course ◽

Immune Cell ◽

Infectious Complications ◽

Hypothalamic Pituitary Adrenal ◽

Immune Organs ◽

High Incidence

Introduction: Cardiac arrest (CA) is associated with high mortality and morbidity, which is in part due to infectious complications developed in CA patients. Infection complications, particularly pneumonia, occur in approximately 60% of CA patients. Given this high incidence, we hypothesized that after CA, the immune system is impaired, which increases the susceptibility of CA patients to potential infections. Therefore, in this study, we systematically examined the immune response in the brain and peripheral immune organs after CA. Methods: Mice were subjected to CA and cardiopulmonary resuscitation (CA/CPR). Flow cytometry, ELISA, immunohistochemistry, and quantitative PCR were used to analyze the immune response in various post-CA organs. Results: First, we characterized the time course of the immune response in the spleen after CA/CPR. CA/CPR induced significant changes in all major immune cell populations. Notably, B cell frequencies decreased, while T cell frequencies increased, in various organs on day 3 post-CA. Further, the levels of pro-inflammatory cytokines, eg IL-6, were markedly increased in the blood and brain after CA. Critically, we found that the lymphocyte counts in the spleen and thymus were dramatically lower in CA mice than in sham mice. Interestingly, CA/CPR caused progressive atrophy of the spleen and thymus. Since it has been shown that CA/CPR alters activity of the hypothalamic-pituitary-adrenal (HPA) axis, we speculated that CA-induced atrophy of lymphoid organs is mediated by the HPA axis. Thus, we treated CA mice with RU486, a glucocorticoid receptor antagonist. Indeed, this treatment reversed CA-induced organ atrophy and mitigated immune cell depletion, both in the thymus and spleen. Conclusions: We provided for the first time evidence that CA/CPR rapidly induced a systemic inflammatory response followed by impairment of the immune system, which eventually led to a massive loss of immune cells in the peripheral immune organs. This CA-induced immunodeficiency appears to be mediated by dysregulation of the HPA axis. Our findings here may be of high clinical significance, considering the high incidence of infectious complications in CA patients and their detrimental effects on CA outcome.

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The Role of Stress in Interpreting the Dexamethasone Suppression Test

The Canadian Journal of Psychiatry ◽

10.1177/070674379203701009 ◽

1992 ◽

Vol 37 (10) ◽

pp. 724-727 ◽

Cited By ~ 1

Author(s):

Jane Blouin ◽

Eric Spindler ◽

Edgardo Perez ◽

Arthur Blouin ◽

Steven Hotz ◽

...

Keyword(s):

Environmental Stress ◽

Psychological Assessment ◽

Confounding Factor ◽

Dexamethasone Suppression Test ◽

Blood Tests ◽

Routine Administration ◽

Suppression Test ◽

Cortisol Suppression ◽

Dexamethasone Suppression

Stress has been implicated as a major confounding factor in the interpretation of Dexamethasone Suppression Test (DST) results. This study was designed to examine the effects of stress on DST results. Fifty patients with high levels of acute, chronic, and environmental stress participated in the study. Each patient was given a comprehensive psychiatric and psychological assessment, a routine administration of dexamethasone, and blood tests of cortisol values. The results indicate that the three measures of stress do not appear to affect levels of cortisol suppression, however, all three measures of stress predicted depression. As expected, DST cortisol levels were related to depression. Results are discussed in terms of their implications for understanding the associations among stress, depression and DST results.

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

The British Journal of Psychiatry ◽

10.1192/bjp.155.4.468 ◽

1989 ◽

Vol 155 (4) ◽

pp. 468-478 ◽

Cited By ~ 48

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.

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