•SAM system and HPA axis reactivity predict future health and disease outcomes.•Exaggerated and blunted responses predict different health and disease outcomes.•Reactivity-related health and disease ...outcomes are both physical and mental.•Intermediate stress responses (“Goldilocks” responses) may be the most adaptive.•A “bidirectional multi-system reactivity hypothesis” is proposed.
Acute psychological stress activates the sympatho-adrenal medullary (SAM) system and hypothalamo-pituitary adrenal (HPA) axis. The relevance of this stress reactivity to long-term health and disease outcomes is of great importance. We examined prospective studies in apparently healthy adults to test the hypothesis that the magnitude of the response to acute psychological stress in healthy adults is related to future health and disease outcomes.
We searched Medline Complete, PsycINFO, CINAHL Complete and Embase up to 15 Aug 2019. Included studies were peer-reviewed, English-language, prospective studies in apparently healthy adults. The exposure was acute psychological stress reactivity (SAM system or HPA axis) at baseline. The outcome was any health or disease outcome at follow-up after ≥1 year.
We identified 1719 papers through database searching and 1 additional paper through other sources. Forty-seven papers met our criteria including 32,866 participants (range 30–4100) with 1−23 years of follow-up. Overall, one third (32 %; 83/263) of all reported findings were significant and two thirds (68 %; 180/263) were null. With regard to the significant findings, both exaggerated (i.e. high) and blunted (i.e. low) stress reactivity of both the SAM system and the HPA axis at baseline were related to health and disease outcomes at follow-up. Exaggerated stress reactivity at baseline predicted an increase in risk factors for cardiovascular disease and decreased telomere length at follow-up. In contrast, blunted stress reactivity predicted future increased adiposity and obesity, more depression, anxiety and PTSD symptoms, greater illness frequency, musculoskeletal pain and regulatory T-Cell percentage, poorer cognitive ability, poorer self-reported health and physical disability and lower bone mass.
Exaggerated and blunted SAM system and HPA axis stress reactivity predicted distinct physical and mental health and disease outcomes over time. Results from prospective studies consistently indicate stress reactivity as a predictor for future health and disease outcomes. Dysregulation of stress reactivity may represent a mechanism by which psychological stress contributes to the development of future health and disease outcomes.
In most healthy people morning awakening is associated with a burst of cortisol secretion: the cortisol awakening response (CAR). It is argued that the CAR is subject to a range physiological ...regulatory influences that facilitate this rapid increase in cortisol secretion. Evidence is presented for reduced adrenal sensitivity to rising levels of ACTH in the pre-awakening period, mediated by an extra-pituitary pathway to the adrenal from the suprachiasmatic nucleus (SCN). A role for the hippocampus in this pre-awakening regulation of cortisol secretion is considered. Attainment of consciousness is associated with ‘flip-flop’ switching of regional brain activation, which, it is argued, initiates a combination of processes: (1) activation of the hypothalamic pituitary adrenal (HPA) axis; (2) release of pre-awakening reduced adrenal sensitivity to ACTH; (3) increased post-awakening adrenal sensitivity to ACTH in response to light, mediated by a SCN extra-pituitary pathway. An association between the CAR and the ending of sleep inertia is discussed.
Highlights • Obtaining meaningful data of the CAR requires attention to methodological detail. • The ISPNE initiated an expert panel to establish quality standards of CAR assessment. • The results of ...this initiative are summarized. • Detailed methodological considerations are outlined and discussed. • Agreed consensus guidelines are presented.
Contact with green space in the environment has been associated with mental health benefits, but the mechanism underpinning this association is not clear. This study extends an earlier exploratory ...study showing that more green space in deprived urban neighbourhoods in Scotland is linked to lower levels of perceived stress and improved physiological stress as measured by diurnal patterns of cortisol secretion. Salivary cortisol concentrations were measured at 3, 6 and 9 h post awakening over two consecutive weekdays, together with measures of perceived stress. Participants (n = 106) were men and women not in work aged between 35-55 years, resident in socially disadvantaged districts from the same Scottish, UK, urban context as the earlier study. Results from linear regression analyses showed a significant and negative relationship between higher green space levels and stress levels, indicating living in areas with a higher percentage of green space is associated with lower stress, confirming the earlier study findings. This study further extends the findings by showing significant gender differences in stress patterns by levels of green space, with women in lower green space areas showing higher levels of stress. A significant interaction effect between gender and percentage green space on mean cortisol concentrations showed a positive effect of higher green space in relation to cortisol measures in women, but not in men. Higher levels of neighbourhood green space were associated with healthier mean cortisol levels in women whilst also attenuating higher cortisol levels in men. We conclude that higher levels of green space in residential neighbourhoods, for this deprived urban population of middle-aged men and women not in work, are linked with lower perceived stress and a steeper (healthier) diurnal cortisol decline. However, overall patterns and levels of cortisol secretion in men and women were differentially related to neighbourhood green space and warrant further investigation.
The cortisol awakening response (CAR) is frequently assessed in psychobiological (stress) research. Obtaining reliable CAR data, however, requires careful attention to methodological detail. To ...promote best practice, expert consensus guidelines on the assessment of the CAR were published (Stalder et al., 2016, PNEC). However, it is unclear whether these highly cited guidelines have resulted in actual methodological improvements. To explore this, the PNEC editorial board invited the present authors to conduct a critical evaluation and update of current CAR methodology, which is reported here. (i) A quantitative evaluation of methodological quality of CAR research published in PNEC before and after the guidelines (2013–2015 vs. 2018–2020) was conducted. Disappointingly, results reveal little improvement in the implementation of central recommendations (especially objective time verification) in recent research. (ii) To enable an update of guidelines, evidence on recent developments in CAR assessment is reviewed, which mostly confirms the accuracy of the majority of the original guidelines. Moreover, recent technological advances, particularly regarding methods for the verification of awakening and sampling times, have emerged and may help to reduce costs in future research. (iii) To aid researchers and increase accessibility, an updated and streamlined version of the CAR consensus guidelines is presented. (iv) Finally, the response of the PNEC editorial board to the present results is described: potential authors of future CAR research to be published in PNEC will be required to submit a methodological checklist (based on the current guidelines) alongside their article. This will increase transparency and enable reviewers to readily assess the quality of the respective CAR data. Combined, it is hoped that these steps will assist researchers and reviewers in assuring higher quality CAR assessments in future research, thus yielding more reliable and reproducible results and helping to further advance this field of study.
•CAR assessment guidelines published in 2016, but unknown if followed by research.•Quantitative evaluation results: Main guidelines are still not consistently followed.•Evidence of recent developments in CAR methodology is reviewed.•Updated CAR consensus guidelines are presented.•Future CAR submissions to PNEC have to fill in checklist based on guidelines.
Abstract
The cortisol awakening response (CAR) is a much studied but poorly understood aspect of the circadian pattern of cortisol secretion. A Scopus search of "cortisol" and "awakening" reveals 666 ...publications in this area since 1997 when it was first identified by Pruessner and colleagues as a "reliable biomarker of adrenocortical activity". The primary focus of the majority of these studies is centered on its utility as a biomarker associated with a range of psychosocial, physical and mental health variables. Such studies typically examine differences in the CAR (studied on 1 or 2 days) between healthy participants and other comparator groups of interest. Fewer studies (25 in our estimation) have examined correlates of day-to-day variation in the CAR in healthy participants, informing its role and regulation within the healthy circadian pattern of cortisol secretion. This is the first review to examine these studies which, although limited in number, offer a relatively coherent emerging story about state factors that influence the CAR and the impact of the CAR on daily functioning. Greater understanding of these issues helps illuminate the utility of the CAR as a promising biomarker in psychophysiological and epidemiological research. The review also highlights areas that require greater clarification and points to potentially fruitful areas of further research.
Parkinson's Disease (PD) is a prevalent and complex age-related neurodegenerative condition for which there are no disease-modifying treatments currently available. The pathophysiological process ...underlying PD remains incompletely understood but increasing evidence points to multiple system dysfunction. Interestingly, the past decade has produced evidence that exercise not only reduces signs and symptoms of PD but is also potentially neuroprotective. Characterizing the mechanistic pathways that are triggered by exercise and lead to positive outcomes will improve understanding of how to counter disease progression and symptomatology. In this review, we highlight how exercise regulates the neuroendocrine system, whose primary role is to respond to stress, maintain homeostasis and improve resilience to aging. We focus on a group of hormones - cortisol, melatonin, insulin, klotho, and vitamin D - that have been shown to associate with various non-motor symptoms of PD, such as mood, cognition, and sleep/circadian rhythm disorder. These hormones may represent important biomarkers to track in clinical trials evaluating effects of exercise in PD with the aim of providing evidence that patients can exert some behavioral-induced control over their disease.
Summary The process of morning awakening is associated with a marked increase in cortisol secretion, the cortisol awakening response (CAR), as well as with a burst in cardiovascular (CV) activation. ...Whilst the CAR is largely driven by awakening-induced activation of hypothalamic–pituitary–adrenal axis, it is fine-tuned by direct sympathetic input to the adrenal gland. In parallel, awakening-induced activation of the CV system is associated with a shift towards dominance of the sympathetic branch of the autonomic nervous system. Moreover, the CAR, in common with trait-like heart rate variability (HRV), is widely reported to be associated with psychosocial variables and health outcomes. These commonalities led us to examine associations between the CAR and both concurrent awakening-induced changes and trait-like estimates in cardiovascular activity (heart rate (HR) and HRV). Self-report measures of difficulties in emotion regulation and chronic stress were also obtained. Forty-three healthy participants (mean age: 23 years) were examined on two consecutive weekdays. On both days, heart interbeat interval (IBI) data was obtained from sedentary laboratory recordings as well as from recordings over the peri-awakening period. Salivary free cortisol concentrations were determined on awakening and 15, 30, and 45 min post-awakening on both study days. Data from a minimum of 36 participants were available for individual analyses. Results revealed significant awakening-induced changes in cortisol, HR and HRV measures; however, no associations were found between the simultaneous post-awakening changes of these variables. Similarly, awakening-induced changes in cortisol, HR and HRV measures were not significantly associated with perceived stress or measures of emotion regulation. However, the CAR was found to be significantly positively correlated with steady state measures of HR and negatively correlated with steady state measures of HRV, as determined during the laboratory sessions and the peri-awakening periods. This cross-sectional study indicates that, despite consistent associations between the CAR and indices of trait-like cardiovascular activity, the CAR is not related to concurrent changes of cardiac autonomic activation following awakening.
Summary The current study investigated intra-individual associations between psychosocial state variables and the cortisol awakening response (CAR) in a detailed case study of a 27-year-old healthy ...male (TS) carried out over 50 measurement days, occurring at 3-day intervals. Quantitative diaries capturing psychosocial states were filled out on the evening before each study day as well as 45 min post-awakening on the study day. On each study day, salivary free cortisol was determined at 0, 15, 30, and 45 min post-awakening. Relationships between cortisol measures and psychosocial variables were analysed using correlation analyses and relative predictive input of independent variables was further determined using linear regression analysis. Significant relationships were found between psychosocial state variables and the dynamic of the CAR (area under increase curve; AUCI ). The final regression model for the AUCI (explaining ∼22% of its variability), included an inverse relationship with the level of prior-day happiness and a positive relationship with study-day anticipations of the level of obligations/no leisure. The results are discussed within the context of previous evidence and potential implications for cross-sectional research are highlighted.
Summary The aim of this study was to investigate the relationship between the cortisol awakening response (CAR) and two key state variables (morning stress and arousal) and the trait-like variable of ...seasonality as recent evidence suggests that the CAR is subject to both state and trait influences. The CAR was examined across two consecutive winter days in 50 healthy participants. Participants collected saliva samples in the domestic setting immediately on awakening, then at 15, 30 and 45 min post-awakening on the two study days. Concomitant trait and state measures were examined, notably seasonal changeability in mood as a trait, and self-reported stress and arousal as state measures. Although there was correlational stability for measures of the CAR across days, there was a significant difference in the magnitude of the increase in cortisol levels following awakening between the two study days, being greater on the first sampling day. This reduction in the magnitude of cortisol increase was significantly associated with an observed reduction across the 2 days in self-reported arousal assessed at 45 min following awakening. Participants reported greater arousal (more alert, active, energetic and stimulated, less drowsy, tired and sluggish) on the first study day than the second. Average CAR across days was associated with seasonality score, greater propensity for seasonal changes in mood being associated with smaller average CAR. High seasonality scorers were also more likely as a group to show a strong association between daily changes in state arousal and CAR. This study supports the view that the CAR is, in part, susceptible to short-term changes in state variables, notably perceived arousal, while observing a novel link between CAR and the trait variable of perceived seasonality. Finally a tentative finding suggests the importance of examining for possible interaction between trait and state effects, evidenced by a significantly greater association between state arousal changes and cortisol response changes in those with high (trait) seasonality.
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