Elevated Cortisol Awakening Response Research Articles

0732 Poor Perinatal Sleep Quality Is Associated with an Elevated Cortisol Awakening Response

0732 Poor Perinatal Sleep Quality Is Associated with an Elevated Cortisol Awakening Response

Exploring associations between diurnal cortisol, stress, coping and psychopathology in adolescents and young adults with 22q11.2 deletion syndrome

Background22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated to a high risk for psychiatric disorders, including psychosis. Individuals with 22q11DS are thought to experience increased levels of chronic stress, which could lead to alterations in hypothalamic-pituitary-adrenocortical (HPA)-axis functioning. In the current study, we investigated for the first time diurnal salivary cortisol profiles in adolescents and young adults with 22q11DS as well as their link with stress exposure, coping strategies and psychopathology, including psychotic symptoms. MethodsSalivary cortisol was collected from adolescents and young adults with 22q11DS (n = 30, age = 19.7) and matched healthy controls (HC; n = 36, age = 18.5) six times a day for two days. Exposure to stressful life events, including peer victimization, coping strategies and general psychopathology were assessed with questionnaires. Psychotic symptoms and psychiatric comorbidities were evaluated with clinical interviews. ResultsWe observed similar daily levels and diurnal profiles of salivary cortisol in adolescents and young adults with 22q11DS compared to HCs. However, participants with 22q11DS reported less frequent exposure to stress than HCs. In 22q11DS, we observed a significant association between the use of non-adaptive coping strategies and the severity of psychotics symptoms. Cortisol level was not associated to severity of psychotic symptoms, but elevated cortisol awakening response (CAR) was found in participants with 22q11DS with higher levels of general psychopathology. ConclusionsOur results do not support earlier propositions of altered HPA-axis functioning in 22q11DS but highlight the need to further investigate diurnal cortisol as an indicator of HPA-axis functioning and its link with (earlier) stress exposure and psychopathology in this population. Interventions should target the development of adaptive coping skills in preventing psychosis in 22q11DS.

Caregiver subjective and physiological markers of stress and patient heart failure severity in family care dyads

Greater family caregiver exposure to uncontrolled patient symptoms is predictive of greater caregiver psychological and physiological stress in dementia and other chronic illnesses, but these phenomena have not been well-studied in heart failure (HF) – a disease with high symptom burden. The purpose of this study was to test the hypothesis that worse patient functional status (as reflected by increasing HF symptoms) would be associated with elevated psychological and physiological stress for the caregiver. This was a secondary analysis of data from 125 HF caregivers in the Caregiver Opportunities for Optimizing Lifestyle (COOL) study. Psychological stress was measured on four dimensions: care-related strain/burden (Oberst Caregiving Burden Scale), depression (Center for Epidemiological Studies Depression Scale), anxiety (State-Trait Anxiety Index), and general stress (Perceived Stress Scale). Physiological stress was measured by markers of HPA axis function (elevated cortisol awakening response [CAR]), endothelial dysfunction (increased PAI-1), and inflammation (increased IL-6, hsCRP). HF patient functional status was quantified by caregiver assessment of New York Heart Association (NYHA) Class. Generalized linear models were used to test associations between patient NYHA Class and stress (one model per indicator). NYHA Class (ordinal) was backwards difference coded in each model to examine caregiver stress in relation to increasing levels of HF severity. Caregivers were mostly female and in their mid-fifties, with a slight majority of the sample being African American and the patient’s spouse. Overall, patient functional status was associated with greater caregiver psychological and physiological stress. In terms of psychological stress, higher NYHA Class was significantly associated with greater caregiver anxiety and general stress, but not with caregiver burden or depression. In terms of physiological stress, higher NYHA Class was associated with elevated markers in all models (elevated CAR and higher IL-6, hsCRP, and PAI-1). Across models, most associations between NYHA Class and stress were present at relatively early stages of functional limitation (i.e. Class II), while others emerged when functional limitations became more severe. To inform timing and mechanisms for much-needed caregiver interventions, research is needed to determine which aspects of HF symptomatology are most stressful for caregivers across the HF trajectory.

Associations between age and cortisol awakening response in patients with borderline personality disorder

Patients with borderline personality disorder (BPD) often display increased stress vulnerability, which may be linked to altered hypothalamus–pituitary–adrenal (HPA) axis functioning. Corresponding deviations of the cortisol awakening response (CAR) are presumed to mirror maladaptive neuroendocrine processes, which may explain why CARs are increased compared to healthy controls (HC). Prior research speculated that these alterations may be caused by early life stress and/or chronic stress related to the ongoing burden of the disorder. Yet, it remains to be investigated how BPD influences CAR in the course of development. Therefore, the current study examined CAR in female adolescents and adults with BPD compared to HC with a particular focus on associations with age. These potential associations were especially focused, as it was hypothesized that the CAR would be even more elevated (i.e., higher) in older individuals with BPD. CAR was assessed in 54 female individuals with BPD (aged 15–40 years) and 54 sex-, age-, and intelligence-matched HC (aged 15–48 years). Group differences were investigated and analyses of covariance using age as continuous predictor were performed to analyze potential developmental associations with CAR alongside BPD-specific effects. Pearson’s correlations were calculated to examine associations between CAR and age. Analyses were repeated with potential confounders as control factors. Results not only demonstrated increased CARs in female individuals with BPD compared to HC but demonstrated elevated CARs with increasing age in BPD individuals exclusively. Effects remained stable after controlling for potential confounders. Thereby, findings suggest that endocrine alterations in BPD may reinforce with increasing age and BPD chronicity.

Abstract 229: Family Caregiver Stress and Patient Symptom Severity in Heart Failure

Background: In chronic illness caregiving, greater family caregiver exposure to patient symptoms is predictive of greater caregiver psychological and physiological stress. Although heart failure (HF) carries high symptom burden, this phenomena is not well-studied in HF caregivers. Objective: To test the hypothesis that caregiver perception of patient HF symptoms is associated with elevated caregiver psychological and physiological stress. Methods: This was a secondary analysis of baseline data from 125 HF caregivers in the Caregiver Opportunities for Optimizing Lifestyle (COOL) study. Psychological stress was measured by caregiver report of care-related strain (Oberst Caregiving Burden Scale), depression (Center for Epidemiological Studies Depression), anxiety (State-Trait Anxiety Index), and general stress (Perceived Stress Scale). Physiological stress was quantified by markers of HPA axis dysfunction (elevated cortisol awakening response [CAR]), endothelial dysfunction (increased PAI-1), and inflammation (increased IL-6, hsCRP). HF symptoms were quantified by caregiver assessment of New York Heart Association (NYHA) Class, dichotomized as asymptomatic [Class I] versus symptomatic [Class II-IV]. Generalized linear models were used to test relationships between symptoms and stress (one model per indicator). IL-6, hsCRP, and PAI-1 were natural log transformed, and CAR was dichotomized based on a cutoff for elevated stress response (>75% increase). All models controlled for sociodemographic confounders (age, gender, race, education, caregiving relationship), with biomarker-specific confounders (comorbidity, adiposity, medications) added to physiological stress models. Results: Caregivers were mostly female (n=115, 92.0%), in their mid-fifties (55.4±11.5), African American (n=72, 57.6%), and the patient’s spouse (n=68, 54.4%) or adult child (n=30, 24.0%). One quarter perceived the patient to be asymptomatic (Class I: n=31, 24.8%; II: n=31, 24.8%; III: n=47, 37.6%; IV: n=15, 12.0%). Symptomatic HF was significantly associated with greater caregiver depression, anxiety, and general stress (β=4.0±1.9, p=0.04; β=3.9±1.4, p<0.01; and β=7.7±2.9, p<0.01, respectively), but not greater care-related strain (β=4.7±3.0, p=0.12). Symptomatic HF was also significantly associated with markers of HPA-axis dysfunction (elevated CAR: OR=3.1, 95% CI=1.0-9.7, p=0.05), endothelial dysfunction (PAI-1: β=0.39±0.16, p=0.01), and increased inflammation as measured by hsCRP (β=0.47±0.22, p=0.04), but not IL-6 (β=0.18±0.15, p=0.21). Conclusions: Overall, patient HF symptoms were associated with greater caregiver psychological and physiological stress. To inform timing and mechanisms for much-needed caregiver interventions, research is needed to determine which aspects of HF symptomatology are most stressful for caregivers across the HF trajectory.

Poor inhibition of personally-relevant facial expressions of sadness and anger predicts an elevated cortisol response following awakening six months later

Failure to inhibit interference from distracting emotional stimuli may obstruct an individual's ability to regulate their behavioural and emotional responses to environmental stressors. Few studies have examined the longitudinal association between cognitive inhibition and regulation of the hypothalamic-pituitary-adrenal axis (HPA) in the natural environment. Seventy-nine healthy adults underwent two assessments 6 months apart. Participants' ability to suppress interference from distracting emotional stimuli was assessed using a negative affective priming task that included both generic and personally-relevant (i.e., participants' intimate partners) facial expressions of emotion. Poorer inhibition of personally-relevant sad and angry faces, but not generic stimuli, significantly predicted an increased cortisol awakening response (CAR) six months later. Moreover, poor inhibition of personally-relevant sad faces mediated the relation between chronic stress and an elevated CAR. Difficulties inhibiting personally-relevant emotional information may represent a key mechanism in understanding how environmental stress influences HPA functioning.

Self-critical perfectionism and depression maintenance over one year: The moderating roles of daily stress-sadness reactivity and the cortisol awakening response.

This study of depressed outpatients (N = 43) examined daily stress-sadness reactivity and the cortisol awakening response (CAR) as moderators of the relationship between self-critical (SC) perfectionism and depression over one year. Participants completed perfectionism measures at baseline (Time 1), daily diaries and salivary sampling six months later (Time 2), and an interviewer-rated depression measure at Time 1, Time 2, and one year after baseline (Time 3). Hierarchical multiple regression analyses of moderator effects demonstrated that patients with higher SC perfectionism and higher levels of daily stress-sadness reactivity (i.e., greater increases in daily sadness in response to increases in daily stress) had less improvement in depressive symptoms at Time 3 relative to those of other patients, adjusting for the effects of Time 1 and Time 2 depression. Furthermore, higher SC perfectionism in conjunction with an elevated CAR predicted higher levels of depression at Time 3. In addition, lower SC perfectionism in combination with higher levels of stress-sadness reactivity/CAR was associated with the lowest levels of depression at Time 3. These findings highlight the importance of targeting dysfunctional self-critical characteristics that exacerbate the impact of heightened stress-sadness reactivity and CAR to generate better treatment outcomes for patients with higher SC perfectionism. (PsycINFO Database Record

Elevated cortisol awakening response associated with early life stress and impaired executive function in healthy adult males

Experiencing early life stress (ELS) and subsequent dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may play a role in the aetiology of mental health disorders. However, the exact mechanisms linking HPA-axis dysregulation with the development of psychopathology have not been fully delineated. Progress in this area is hampered by the complex and often conflicting associations found between markers of HPA-axis function and risk factors for mental health disorders such as impaired executive function (EF) and ELS. This study investigated the association of the cortisol awakening response (CAR) with ELS and EF in a healthy adult male population (n=109, aged 21–63). As previous inconsistencies in CAR and ELS association studies may be the result of not considering ELS-related factors such as cumulative exposure, type of stressor and developmental timing of ELS, these were also investigated. The main findings were that the CAR was significantly elevated in individuals reporting ELS compared to those reporting no ELS (p=0.007) and that an elevated CAR predicted poorer problem solving/planning (p=0.046). Cumulative exposure, type of stressor and developmental timing of ELS were also found to impact significantly on the CAR. These results suggest that ELS is associated with chronic changes in HPA-axis function and that these changes may be associated with impairments in problem solving/planning. Future work should investigate further the neurobiological mechanisms linking ELS, the CAR and EF and their role in conferring risk for the development of mental health disorders.

The cortisol awakening response in anxiety disorders and personality disorders and changes in salivary cortisol level after psychotherapy

IntroductionThe hypothalamus—pituitary—adrenal axis (HPA axis) dysregulation plays an important role in the pathophysiology of anxiety disorders. Salivary cortisol level is a useful indicator of HPA axis dysfunction.ObjectivesMost data suggests elevated cortisol awakening response (CAR) in anxiety disorders, but there are studies indicating opposite pattern (flat CAR).AimGoal of this study was to determine whether patients with anxiety and personality disorders show a specific daily cortisol patterns and weather this pattern changes after 12 weeks of intensive predominantly psychodynamic combined group and individual psychotherapy.MethodThe studied population comprised 77 patients, mainly females (72.7%), with primary diagnosis of anxiety disorder 40.9% or personality disorder 59.1%. The Symptom Checklist “0” was used to assess the pre- and post-treatment levels of patients’ symptoms. Pre- and post-treatment cortisol levels were measured in three saliva samples collected during one day (at awakening, 30 min after awakening, at 22.00).ResultsThe obtained results were partly similar to previous research. We found four different daily CAR patterns: decreased (drop 30 min after awakening), flat (rise 0–49% 30 min after awakening), normal (rise 50–75% 30 min after awakening) and elevated (rise over 75% 30 min after awakening), two of them (flat and elevated) were considered as typical for anxiety disorders. Groups of CAR pattern differed significantly in the level of sleep symptoms, dysthymia symptoms and avoidance/dependency symptoms. The changes in the CAR pattern after psychotherapy were not significant.ConclusionsAnxiety disorders and personality disorders are characterized by more than two specific daily salivary cortisol patterns.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Emotion Regulation Regulates More than Emotion: Associations of Momentary Emotion Regulation with Diurnal Cortisol in Current and Past Depression and Anxiety.

Maladaptive emotion regulation and dysregulated hypothalamic-pituitary-adrenal (HPA) axis functioning are characteristic of depression and anxiety. However, little research examines whether and how emotion regulation affects HPA axis functioning. We utilized an experience sampling methodology to examine associations between three emotion regulation strategies (problem solving, disengagement, and emotional expression/support seeking) and diurnal cortisol rhythms and reactivity in everyday life. Participants were young adults with current, past, or no history of internalizing disorders (depression or anxiety; N = 182). Across participants, problem solving was associated with an elevated cortisol awakening response (CAR) while disengagement was associated with a steeper cortisol slope. Only for individuals with internalizing disorders was momentary problem solving and emotional expression/support seeking associated with higher cortisol reactivity and emotional expression/support seeking associated with a flatter diurnal slope and blunted CAR. Results provide insight into associations between emotion regulation and day-to-day HPA-axis functioning.

The Cortisol Awakening Response and Depressive Symptomatology: The Moderating Role of Sleep and Gender.

The association between depression and the cortisol awakening response (CAR) has been widely examined, yet the results are mixed and factors responsible for such inconsistencies are poorly understood. The current study investigated whether the link between depressive symptomatology and CAR varied as a function of two such factors: sleep and gender. The sample included 58 young adults (30 females; Mage = 18.7; SDage = 0.91). Participants completed the Beck Depression Inventory as well as the Consensus Sleep Diary to assess depressive symptomatology and daily sleep patterns, respectively. Participants also provided four salivary cortisol samples (0, 30, 45 and 60 min after awakening) during two consecutive weekdays. Results demonstrated that greater depressive symptoms were associated with a greater CAR but only when depressive symptoms were linked to a shorter sleep time. In addition, gender significantly moderated the association between depressive symptoms and CAR. While greater depressive symptoms were associated with an elevated CAR among females, they were associated with a blunted CAR among males. These findings provide some insight into potential mechanisms linking depressive symptomatology and CAR, and suggest that future studies examining CAR as a biomarker of depression should account for differences in sleep and gender. Copyright © 2016 John Wiley & Sons, Ltd.

Cortisol awakening response in drug-naïve panic disorder.

BackgroundIt is unclear whether hypothalamic–pituitary–adrenal axis is involved in the pathophysiology of panic disorder (PD). The findings remain inconsistent. Cortisol awakening response (CAR) is a noninvasive biomarker of stress system activity. We designed the study to assess CAR in drug-naïve PD patients.Materials and methodsWe assessed CAR in 14 psychotropic drug-naïve outpatients with PD and 14 healthy controls. The severity of PD was assessed with Panic and Agoraphobia Scale. The severity of anxiety and depression was screened with Hospital Anxiety and Depression Scale.ResultsNo significant difference in CAR between PD patients and control group was found. No correlations were observed between CAR and anxiety severity measures in PD patients and controls.LimitationsThe number of participating subjects was relatively small, and the study results apply to nonsuicidal drug-naïve PD patients without agoraphobia and with short-illness duration. There was a lack of control on subjects’ compliance with the sampling instructions.ConclusionThe study provides no support for elevated CAR levels in drug-naïve PD patients without agoraphobia.

Circadian disruption and biomarkers of tumor progression in breast cancer patients awaiting surgery

Psychological distress, which can begin with cancer diagnosis and continue with treatment, is linked with circadian and endocrine disruption. In turn, circadian/endocrine factors are potent modulators of cancer progression. We hypothesized that circadian rest-activity rhythm disruption, distress, and diurnal cortisol rhythms would be associated with biomarkers of tumor progression in the peripheral blood of women awaiting breast cancer surgery. Breast cancer patients (n=43) provided actigraphic data on rest-activity rhythm, cancer-specific distress (IES, POMS), saliva samples for assessment of diurnal cortisol rhythm, cortisol awakening response (CAR), and diurnal mean. Ten potential markers of tumor progression were quantified in serum samples and grouped by exploratory factor analysis. Analyses yielded three factors, which appear to include biomarkers reflecting different aspects of tumor progression. Elevated factor scores indicate both high levels and strong clustering among serum signals. Factor 1 included VEGF, MMP-9, and TGF-β; suggesting tumor invasion/immunosuppression. Factor 2 included IL-1β, TNF-α, IL-6R, MCP-1; suggesting inflammation/chemotaxis. Factor 3 included IL-6, IL-12, IFN-γ; suggesting inflammation/TH1-type immunity. Hierarchical regressions adjusting age, stage and socioeconomic status examined associations of circadian, distress, and endocrine variables with these three factor scores. Patients with poor circadian coordination as measured by rest-activity rhythms had higher Factor 1 scores (R(2)=.160, p=.038). Patients with elevated CAR also had higher Factor 1 scores (R(2)=.293, p=.020). These relationships appeared to be driven largely by VEGF concentrations. Distress was not related to tumor-relevant biomarkers, and no other significant relationships emerged. Women with strong circadian activity rhythms showed less evidence of tumor promotion and/or progression as indicated by peripheral blood biomarkers. The study was not equipped to discern the cause of these associations. Circadian/endocrine aberrations may be a manifestation of systemic effects of aggressive tumors. Alternatively, these results raise the possibility that, among patients with active breast tumors, disruption of circadian activity rhythms and elevated CAR may facilitate tumor promotion and progression.

Hormonal Treatment Reduces Psychobiological Distress in Gender Identity Disorder, Independently of the Attachment Style

Gender identity disorder may be a stressful situation. Hormonal treatment seemed to improve the general health as it reduces psychological and social distress. The attachment style seemed to regulate distress in insecure individuals as they are more exposed to hypothalamic-pituitary-adrenal system dysregulation and subjective stress. The objectives of the study were to evaluate the presence of psychobiological distress and insecure attachment in transsexuals and to study their stress levels with reference to the hormonal treatment and the attachment pattern. We investigated 70 transsexual patients. We measured the cortisol levels and the perceived stress before starting the hormonal therapy and after about 12 months. We studied the representation of attachment in transsexuals by a backward investigation in the relations between them and their caregivers. We used blood samples for assessing cortisol awakening response (CAR); we used the Perceived Stress Scale for evaluating self-reported perceived stress and the Adult Attachment Interview to determine attachment styles. At enrollment, transsexuals reported elevated CAR; their values were out of normal. They expressed higher perceived stress and more attachment insecurity, with respect to normative sample data. When treated with hormone therapy, transsexuals reported significantly lower CAR (P < 0.001), falling within the normal range for cortisol levels. Treated transsexuals showed also lower perceived stress (P < 0.001), with levels similar to normative samples. The insecure attachment styles were associated with higher CAR and perceived stress in untreated transsexuals (P < 0.01). Treated transsexuals did not expressed significant differences in CAR and perceived stress by attachment. Our results suggested that untreated patients suffer from a higher degree of stress and that attachment insecurity negatively impacts the stress management. Initiating the hormonal treatment seemed to have a positive effect in reducing stress levels, whatever the attachment style may be.

Cortisol awakening response and negative emotionality linked to asymmetry in major limbic fibre bundle architecture

The limbic system plays an important role in regulating the hypothalamic–pituitary–adrenal (HPA) axis as well as aspects of emotion, and both neuroendocrine disturbance and increased negative emotionality are associated with risk for developing affective disorders. However, the extent to which the architecture of connections between limbic structures may be linked to individual differences in basal HPA-axis reactivity and negative emotionality is unknown. Here we tested the hypotheses that microstructural asymmetry of the major limbic fibre bundles would be associated with cortisol awakening response (CAR) and neuroticism, a personality trait associated with the tendency to experience negative emotions. Sixty-nine healthy adults were studied with diffusion-weighted imaging, and fractional anisotropy (FA) was extracted from the cingulum and uncinate fasciculus. Higher neuroticism scores, which were associated with higher CAR, were also correlated with higher right relative to left cingulum FA. Elevated CAR was associated with the degree of FA asymmetry within both the cingulum and the uncinate fasciculus, but in opposing directions. These results suggest that the balance between left- and right-sided limbic circuits may bear an important relationship to hypothalamic–pituitary–adrenal axis reactivity, and to the tendency to experience negative emotions, and they raise important questions about the significance of limbic system architecture.

Increased cortisol awakening response and afternoon/evening cortisol output in healthy young adults with low early life parental care

Growing evidence from animal and human studies suggests a profound and long-lasting influence of early life experiences--ranging from variations in parenting behavior to severe adversity--on hypothalamic-pituitary-adrenal axis function. The aim of the current investigation was to examine the association between naturally occurring variations in early life parental care and the cortisol awakening response (CAR), afternoon/evening cortisol output and key psychological variables in a sample of healthy young adults. Fifty-eight (19 male and 39 female) participants between 18 and 30 years of age completed psychological questionnaires and collected saliva at awakening, 30 min thereafter and at 3 p.m., 6 p.m., and 9 p.m. on three non-consecutive weekdays. Participants with low (compared to high) parental care experiences exhibited an increased CAR, increased afternoon/evening cortisol output, decreased self-esteem, and increased depressive symptomatology and anxiety. We suggest that the elevated CAR and afternoon/evening cortisol levels might reflect a biological correlate of adversity-induced vulnerability for psychopathology. This study is first to show an association between the retrospective perception of early life parental care and cortisol circadian rhythms in healthy young adults.

The cortisol awakening response in patients remitted from depression

An impressive number of data has been accumulated on dysfunctions of the hypothalamo-pituitary–adrenal (HPA) axis and cortisol hypersecretion in depression. To assess the dynamic HPA functioning, the cortisol awakening response (CAR) is an easily accessible and reliable approach. Some data suggest that elevated CAR in depressed patients has trait-like characteristics. Therefore we investigated whether patients in remission from a depressive episode have elevated CAR compared to control subjects. CAR of thirty-eight patients in remission from depression (11 men, 27 women, age range 24–66) and 52 control participants were analyzed (18 men, 34 women, age range 24–63). All patients had experienced ≥3 previous depressive episodes and were off psychotropic medication since at least 3 months. Saliva samples were collected only once, at home, either on weekend or weekday at 0, 15, 30, 45 and 60 min post-awakening. The area under the curve ( AUC) above minimum cortisol concentration displayed large interindividual variability (6.4-fold in remitted patients and 8.1-fold in controls, based on 80% range). Investigation of possible variability factors showed that percent explained variance increased from 3.9% when group was considered alone to 8.8%, 12.3% and 19.2% after adjusting for significant effects of weekday vs. weekend, wake-up time and sleep duration, respectively. According to the latter model, AUC was estimated to be 51% higher in remitted patients than in controls ( p = 0.007), while a 21% AUC decrease was associated with a 1-h longer sleep duration ( p < 0.001). In future studies, detection of between-group differences might benefit from adjusting for sleep duration and other possible confounders.