Dysregulated Diurnal Cortisol Pattern and Heightened Night-Time Cortisol in Individuals with Bipolar Disorder

2021 ◽  
pp. 1-9
Author(s):  
Dahlia Mukherjee ◽  
J. Dylan Weissenkampen ◽  
Emily Wasserman ◽  
Venkatesh Basappa Krishnamurthy ◽  
Caitlin E. Millett ◽  
...  

<b><i>Introduction:</i></b> Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may contribute to the symptom burden in bipolar disorder (BD). Further characterization of cortisol secretion is needed to improve understanding of the connection between mood, sleep, and the HPA axis. Here, we observe diurnal cortisol patterns in individuals with BD and healthy controls (HCs) to determine time points where differences may occur. <b><i>Methods:</i></b> Salivary cortisol was measured at 6 time points (wake, 15, 30, and 45 min after wake, between 2:00 and 4:00 p.m. and 10:00 p.m.) for 3 consecutive days in individuals with symptomatic BD (<i>N</i> = 27) and HC participants (<i>N</i> = 31). A general linear model with correlated errors was utilized to determine if salivary cortisol changed differently throughout the day between the 2 study groups. <b><i>Results:</i></b> A significant interaction (<i>F</i> = 2.74, <i>df</i> = 5, and <i>p</i> = 0.02) was observed between the time of day and the study group (BD vs. HC) when modeling salivary cortisol over time, indicating that salivary cortisol levels throughout the day significantly differed between the study groups. Specifically, salivary cortisol in BD was elevated compared to HCs at the 10:00 p.m. time point (<i>p</i> = 0.01). <b><i>Conclusion:</i></b> Significantly higher levels of cortisol in participants with BD in the night-time suggest that the attenuation of cortisol observed in healthy individuals may be impaired in those with BD. Reregulation of cortisol levels may be a target of further study and treatment intervention for individuals with BD.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eleonora Iob ◽  
Jessie R. Baldwin ◽  
Robert Plomin ◽  
Andrew Steptoe

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.


2021 ◽  
pp. 4-7
Author(s):  
Shefali Shefali ◽  
Saurabh Juneja ◽  
Anshi Jain ◽  
Devi Charan Shetty ◽  
Nikita Gulati

The progression and development of OPMDs is inuenced by a multitude of factors which include complex interactions between physiological, psychological, behavioral and social factors. The persistent activation of HPA axis through tobacco usage probably impairs immune response and has a role in progression of OPMDs. The quantication of salivary cortisol facilitates the assessment of nicotine impact on the oral mucosa and in the progression of OPMDs. This study was undertaken to estimate the salivary cortisol levels in the OPMDs with and without habits thereby signifying the importance of salivary cortisol in the causation of disease or as an effective biomarker for disease progression during the pathogenetic process of the disease. Salivary cortisol levels were estimated by ELISA technique in 29 cases of differing grades of oral potentially malignant disorders consisting of individuals with habit and lesions (Group I), 32 cases of individuals having habit without lesions (Group II) and 3 cases of individuals having lesion without habit (Group III) and 8 cases with neither habit nor lesions (Group IV). Salivary cortisol levels were correlated within the different study groups and were analyzed using SPSS (version 20). Salivary cortisol levels were raised in group I as compared to all other groups. Clarity in the present study has been achieved that salivary cortisol levels can be researched to the causation of the disease as an important step forward. This study could open up newer avenues in understanding the pathogenetic mechanisms in Oral Potentially malignant disorders.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A101-A101
Author(s):  
N Goel ◽  
E M Yamazaki ◽  
L E MacMullen ◽  
A J Ecker

Abstract Introduction Individuals show marked differential vulnerability in neurobehavioral deficits from psychosocial stress and sleep deprivation. Although changes in salivary cortisol and C-reactive protein (CRP) typically occur across total sleep deprivation (TSD) and recovery sleep, whether these biological markers during fully rested conditions predict individual differences in cognitive performance during TSD and stress remains unknown. Methods Thirty-one healthy adults (ages 27–53; mean ± SD, 35.4 ± 7.1y; 14 females) participated in a five-day experiment consisting of two 8h time-in-bed (TIB) baseline nights, followed by 39h TSD, and two 8h-10h TIB recovery nights. A modified Trier Social Stress Test (TSST) was conducted on the day of TSD to induce psychological stress. Salivary cortisol and CRP from blood were obtained at six time points during the study (pre-study, baseline, during TSD, during TSD after the TSST, after recovery, and post-study). A median split of TSD performance [total lapses (&gt;500 ms response time) and errors] on the 10-minute Psychomotor Vigilance Test (PVT) defined cognitively resilient (n=15) and cognitively vulnerable (n=16) groups. Repeated measures ANOVA and post-hoc comparisons corrected for multiple testing, examined cortisol and CRP across time points between groups. Results In both cognitively resilient and vulnerable individuals, cortisol increased with TSD compared to baseline in the morning and decreased with TSD + psychological stress in the afternoon compared to TSD alone. By contrast, there were no significant changes in CRP levels throughout the experiment. In addition, there were no significant time*group interactions in cortisol or CRP levels. Conclusion Salivary cortisol increased with TSD compared to baseline and showed a time-of-day effect with stress during TSD. Notably, cortisol and CRP did not differ between cognitively resilient and vulnerable individuals across TSD, psychological stress or recovery sleep and thus are not reliable biomarkers for predicting performance under these conditions. Support NASA NNX14AN49G.


2014 ◽  
Vol 99 (3) ◽  
pp. E464-E468 ◽  
Author(s):  
Hamimatunnisa Johar ◽  
Rebecca T. Emeny ◽  
Martin Bidlingmaier ◽  
Martin Reincke ◽  
Barbara Thorand ◽  
...  

Background: The role of neuroendocrine alterations in the etiology of frailty syndrome is still poorly understood. Hypothalamic-pituitary-adrenal axis dysregulation is a plausible candidate pathway contributing to frailty. Thus, we sought to examine the associations of diurnal cortisol secretion with frailty in older adults. Methods: A cross-sectional analysis was conducted among 745 study participants (age 65–90 years, mean age 75.1 years) of the population-based KORA Age study. Associations between salivary cortisol measures at awakening (morning 1 [M1]), 30 minutes after awakening (M2), and evening (E) and frailty criteria were determined. Results: Lower cortisol levels in the first morning sample (M1) (P = .18) and M2 (P = .14) and increased E levels (P = .004) were observed in prefrail (35.17%, n = 262) and frail (3.36%, n = 25) individuals, in a dose-response manner. Frailty was strongly associated with smaller ratios of morning to evening levels; M1 to E ratio (P = .02) and M2 to E ratio (P = .003). Higher evening cortisol levels were associated with a 24% increased risk of a prefrail state (odds ratio, 1.22; 95% confidence interval, 1.03–1.44). A smaller morning to evening ratio was associated with an increased risk of low grip strength (1.42, 1.09–1.86) and gait speed (1.31, 1.02–1.68). Conclusion: Frailty status is associated with blunted cortisol reactivity as demonstrated by lower morning and higher evening salivary cortisol levels.


2004 ◽  
Vol 184 (6) ◽  
pp. 496-502 ◽  
Author(s):  
Stuart Watson ◽  
Peter Gallagher ◽  
James C. Ritchie ◽  
I. Nicol Ferrier ◽  
Allan H. Young

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.


2020 ◽  
Author(s):  
Cédric Girard-Buttoz ◽  
Patrick J. Tkaczynski ◽  
Liran Samuni ◽  
Pawel Fedurek ◽  
Cristina Gomes ◽  
...  

AbstractIn mammals, early life adversity negatively affects survival and reproductive success. A key causal mechanism is proposed by the biological embedding model which posits that adversity experienced early in life has deleterious consequences on individual physiology across the lifespan. In particular, early life adversity is expected to be a severe stressor leading to long-term alteration of the hypothalamic pituitary adrenal (HPA) axis activity. Here we tested this idea by assessing whether, as in humans, maternal loss had short and long-term impacts on orphan chimpanzee urinary cortisol levels and diurnal urinary cortisol slopes, as an indicator of the HPA axis functioning. We used 18 years of data on 50 immature and 28 mature male wild chimpanzees belonging to four communities in Taï National Park, Ivory Coast. Immature orphans who experienced early maternal loss had diurnal cortisol slopes characterised by higher early morning and late afternoon cortisol levels indicative of high activation of the HPA axis. Recently orphaned immatures had higher cortisol levels than other immatures, possibly reflecting social and nutritional stress. However, unlike in humans, we did not find significantly different cortisol profiles in orphan and non-orphan adult male chimpanzees. Our study highlights that long-term alteration of stress physiology related to early life adversity may not be viable in some wild animal populations and/or that chimpanzees, as humans, may have access to mechanisms that buffer this physiological stress, such as adoption. Our results suggest that biological embedding of altered HPA axis function is unlikely to be a mechanism contributing to the demonstrated long-term fitness consequences of maternal loss, such as reduced reproductive success, in wild long-lived mammals.


2021 ◽  
Vol 10 (18) ◽  
pp. 4230
Author(s):  
Rita Polito ◽  
Giovanni Messina ◽  
Anna Valenzano ◽  
Alessia Scarinci ◽  
Ines Villano ◽  
...  

Adipose tissue is considered an endocrine organ, and its excess compromises the immune response and metabolism of hormones and nutrients. Furthermore, the accumulation of visceral fat helps to increase the synthesis of cortisol. The hypothalamus-pituitary-adrenal (HPA) axis is a neuroendocrine system involved in maintaining homeostasis in humans under physiological conditions and stress, and cortisol is the main hormone of the HPA axis. It is known that a stress-induced diet and cortisol reactivity to acute stress factors may be related to dietary behavior. In obesity, to reduce visceral adipose tissue, caloric restriction is a valid strategy. In light of this fact, the aim of this study was to assess the effects of a commercial dietary ketosis program for weight loss on the sympathetic nervous system and HPA axis, through evaluation of salivary cortisol and GSR levels. Thirty obese subjects were recruited and assessed before and after 8 weeks of Very Low Calorie Ketogenic Diet (VLCKD) intervention to evaluate body composition and biochemical parameters. Salivary cortisol levels and GSR significantly decreased after dietary treatment; in addition, body composition and biochemical features were ameliorated. The VLCKD had a short-term positive effect on the SNS and HPA axes regulating salivary cortisol levels. Finally, the effects of the VLCKD on the SNS and HPA axis may lead to more individualized treatment strategies that integrate obesity and stress and support the usefulness of such therapeutic interventions in promoting the reduction of the individual disease burden.


2016 ◽  
Vol 117 (1) ◽  
pp. 18-33 ◽  
Author(s):  
Michaela Dušková ◽  
Kateřina Šimůnková ◽  
Jana Vítků ◽  
Lucie Sosvorová ◽  
Hana Jandíková ◽  
...  

Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis). The gold standard is still considered the insulin tolerance test (ITT), but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD ±4.8) years, and mean/median BMI (body mass index) 25.38/24.82 (SD ±3.2) kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 μg, 10 μg, and 250 μg Synacthen (ACTH) tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone) were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 μg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results.


Author(s):  
Noriko Matsuura ◽  
Hidemasa Motoshima ◽  
Kenji Uchida ◽  
Yujiro Yamanaka

Abstract Background Lactococcus lactis subsp. cremoris (YRC3780), which is isolated from kefir, has been associated with anti-allergic effects in humans. However, it remains unknown whether daily intake of YRC3780 attenuates the response to psychological stress in humans in parallel with changes to the gut microbiome. We examined the fundamental role of YRC3780 in the gut microbiome, stress response, sleep, and mental health in humans. Methods Effects of daily intake of YRC3780 on the hypothalamic-pituitary-adrenal (HPA) axis response to acute psychological stress were investigated in a double-blind, placebo-controlled clinical trial involving 27 healthy young men (mean age and body mass index: 23.5 years and 21.5 kg/m2) who were randomly assigned to placebo (n = 13) or YRC3780 (n = 14) groups. The HPA axis response to acute psychological stress, the diurnal rhythm of HPA axis activity, and gut microbiome were assessed and compared between the two groups. Results The results showed that daily intake of YRC3780 significantly lowered morning salivary cortisol levels compared with placebo. In addition, salivary cortisol levels following a social stress test significantly decreased +40 min after beginning the TSST in the YRC3780-treated group compared to placebo. There were no significant differences between the two groups in terms of actigraphy-based sleep quality, but the subjective sleep quality and mental health were significantly improved in the YRC3780-treated group compared to placebo. Conclusions Our study suggests that daily intake of YRC3780 improves the HPA axis response to acute psychological stress, which might be associated with a decrease in morning cortisol levels.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Einor Ben Assayag ◽  
Estelle Seyman ◽  
Jeremy Molad ◽  
Oren Tene ◽  
Amos Korczyn ◽  
...  

Background: The short (s) allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is related to reduced serotonin transporter efficiency and an increased vulnerability to stress and mental disorders. The 5-HTTLPR s allele was reported as associate with hypothalamic-pituitary-adrenal (HPA)-axis reactivity to stress, depression and negatively impact on memory. Acute stroke is associated with elevated cortisol levels as part of the body’s reaction to a stress provoking event. We investigated whether 5-HTT genotype interacts with physiological stress to impact on outcome after stroke. Methods: Data from 485 non-depressed cognitively intact first-ever mild to moderate stroke patients from the TABASCO study were available. Patients underwent 3T MRI scans, saliva cortisol measure and comprehensive neuropsychological assessments at admission, 6, and 12 and 24 months thereafter. Results: Carriers of the 5-HTT-s allele (23.2%) had significantly higher admission bedtime salivary cortisol (p=0.042) and more depressive symptoms 12 and 24 months after the index event (p=0.043, p=0.05, respectively) than non-carriers. Higher admission salivary cortisol levels negatively correlated with hippocampal and amigdalar volume at admission (r=-0.257, p=0.004; r=-0.177, p=0.048, respectively) as well as with lower cognitive and higher depression scores 24 months post-stroke (r=-0.2, p=0.032, r=0.245, p=0.007, respectively). The association between salivary cortisol levels, depressive and cognitive scores was stronger in 5-HTT-s carriers than non-carriers. Conclusions: We report that carriers of the 5-HTT-s allele may be at risk to develop depressive symptoms post-stroke. The interactive effects of the s allele and cortisol levels on hippocampal volume and post-stroke depressive symptoms, as well as cognitive performance, suggest that the negative effect of the serotonin polymorphism on the development of post-stroke depression and cognitive decline is mediated by the HPA axis. Since genetic factors may influence vulnerability to the adverse effects of stress, serotonin receptors may provide a novel target for therapeutics to prevent depression and cognitive deterioration in stroke patients.


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