Assessment of the cortisol awakening response: expert consensus guidelines

The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30–45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening. Researchers assessing the CAR thus need to take important steps to maximize and monitor saliva sampling accuracy as well as consider a range of other relevant methodological factors. To promote best practice of future research in this field, the International Society of Psychoneuroendocrinology initiated an expert panel charged with (i) summarizing relevant evidence and collective experience on methodological factors affecting CAR assessment and (ii) formulating clear consensus guidelines for future research. The present report summarizes the results of this undertaking. Consensus guidelines are presented on central aspects of CAR assessment, including objective control of sampling accuracy/adherence, participant instructions, covariate accounting, sampling protocols, quantification strategies as well as reporting and interpreting of CAR data. Meeting these methodological standards in future research will create more powerful research designs, thus yielding more reliable and reproducible results and helping to further advance understanding in this evolving field of research

Dragon-kings: mechanisms, statistical methods and empirical evidence

This introductory article presents the special Discussion and Debate volume "From black swans to dragon-kings, is there life beyond power laws?" published in Eur. Phys. J. Special Topics in May 2012. We summarize and put in perspective the contributions into three main themes: (i) mechanisms for dragon-kings, (ii) detection of dragon-kings and statistical tests and (iii) empirical evidence in a large variety of natural and social systems. Overall, we are pleased to witness significant advances both in the introduction and clarification of underlying mechanisms and in the development of novel efficient tests that demonstrate clear evidence for the presence of dragon-kings in many systems. However, this positive view should be balanced by the fact that this remains a very delicate and difficult field, if only due to the scarcity of data as well as the extraordinary important implications with respect to hazard assessment, risk control and predictability.Comment: 20 page

Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

Differentiating anticipatory from reactive cortisol responses to psychosocial stress

Item does not contain fulltextMost psychosocial stress studies assess the overall cortisol response without further identifying the temporal dynamics within hormone levels. It has been shown, however, that the amplitude of anticipatory cortisol stress levels has a unique predictive value for psychological health. So far, no "best practice" in how to investigate the anticipatory cortisol stress response has emerged. The goal of the current research was to develop a protocol that would allow for a sensitive and easy-to-implement laboratory-based investigation into anticipatory cortisol stress levels. We initially tested 26 healthy men in either an anticipation- or stress-only condition of the Trier Social Stress Test (TSST) to map the distinct timelines of anticipatory and reactive cortisol release profiles (study 1). Subsequently, we administered the TSST to 50 healthy men such that the cortisol responses to anticipatory and reactive stress components could be dissociated (study 2). In both studies we sampled saliva cortisol at high frequency (at baseline, during 10min of anticipation and during and after 10min of acute stress) and the current mood state pre- and post-stress. We found anticipatory responder rates of 20% and 40%, with peak anticipatory cortisol levels between 14 and 20min after onset of anticipation. Visible changes in reactive cortisol levels occurred only after the termination of the acute stressor. We conclude that the best practice to detect a maximum number of anticipatory responders in the TSST would be to extend the anticipation phase to 15min. In doing so, the anticipatory cortisol peak could be captured at a time-point of the actual stressor that is uninfluenced by reactive cortisol levels. Overall, we could reveal several features of anticipatory responders. Most importantly, there was a positive correlation between anticipatory and reactive stress responses. There was no association between anticipatory cortisol and alpha-amylase as well as subjective-psychological stress responses. Future studies will have to determine whether the anticipatory responders differ with respect to various stress-sensitive parameters like sex, personality, psychological wellbeing or chronic stress

Early life stress modulates amygdala-prefrontal functional connectivity: implications for oxytocin effects

Recent evidence suggests that early life stress (ELS) changes stress reactivity via reduced resting state functional connectivity (rs-FC) between amygdala and the prefrontal cortex. Oxytocin (OXT) modulates amygdala connectivity and attenuates responses to psychosocial stress, but its effect appears to be moderated by ELS. Here we first investigate the effect of ELS on amygdala-prefrontal rs-FC, and examine whether ELS-associated changes of rs-FC in this neural circuit predict its response to psychosocial stress. Secondly, we explore the joint effect of OXT and ELS on the amygdala-prefrontal circuit. Eighteen healthy young males participated in a resting-state fMRI study of OXT effects using a double-blind, randomized, placebo-controlled, within-subject crossover design. We measured the rs-FC to bilateral amygdalae and subsequently assessed changes of state anxiety and prefrontal responses to psychosocial stress. Multiple linear regressions showed that ELS, specifically emotional abuse, predicted reduced rs-FC between the right amygdala and pregenual anterior cingulate cortex (pgACC), which in turn predicted elevated state anxiety after psychosocial stress. In subjects with lower ELS scores, stronger pgACC-amygdala rs-FC predicted stronger pgACC deactivation during the psychosocial stress task, and this rest-task interaction was attenuated by OXT. In subjects with higher ELS scores however, the rest-task interaction was altered and OXT showed no significant effect. These findings highlight that ELS reduces pgACC-amygdala rs-FC and alters how rs-FC of this circuit predicts its stress responsiveness. Such changes in pgACC-amygdala functional dynamics may underlie the altered sensitivity to the effects of OXT after ELS