Mapping pathways to neuronal atrophy in healthy, mid-aged adults: From chronic stress to systemic inflammation to neurodegeneration?

Growing evidence implicates systemic inflammation in the loss of structural brain integrity in natural ageing and disorder development. Chronic stress and glucocorticoid exposure can potentiate inflammatory processes and may also be linked to neuronal atrophy, particularly in the hippocampus and the human neocortex. To improve understanding of emerging maladaptive interactions between stress and inflammation, this study examined evidence for glucocorticoid- and inflammation-mediated neurodegeneration in healthy mid-aged adults. N = 169 healthy adults (mean age = 39.4, 64.5% female) were sampled from the general population in the context of the ReSource Project. Stress, inflammation and neuronal atrophy were quantified using physiological indices of chronic stress (hair cortisol (HCC) and cortisone (HEC) concentration), systemic inflammation (interleukin-6 (IL-6), high-sensitive C-reactive protein (hs-CRP)), the systemic inflammation index (SII), hippocampal volume (HCV) and cortical thickness (CT) in regions of interest. Structural equation models were used to examine evidence for pathways from stress and inflammation to neuronal atrophy. Model fit indices indicated good representation of stress, inflammation, and neurological data through the constructed models (CT model: robust RMSEA = 0.041, robust χ2 = 910.90; HCV model: robust RMSEA <0.001, robust χ2 = 40.95). Among inflammatory indices, only the SII was positively associated with hair cortisol as one indicator of chronic stress (ß = 0.18, p < 0.05). Direct and indirect pathways from chronic stress and systemic inflammation to cortical thickness or hippocampal volume were non-significant. In exploratory analysis, the SII was inversely related to mean cortical thickness. Our results emphasize the importance of considering the multidimensionality of systemic inflammation and chronic stress, with various indicators that may represent different aspects of the systemic reaction. We conclude that inflammation and glucocorticoid-mediated neurodegeneration indicated by IL-6 and hs-CRP and HCC and HEC may only emerge during advanced ageing and disorder processes, still the SII could be a promising candidate for detecting associations between inflammation and neurodegeneration in younger and healthy samples. Future work should examine these pathways in prospective longitudinal designs, for which the present investigation serves as a baseline.

Evidence for differential associations of distinct trait mindfulness facets with acute and chronic stress.

Stress and stress-associated disease are considered the health epidemic of the 21st century. Interestingly, despite experiencing similar amounts of stress than those falling ill, some individuals are protected against the "wear and tear of daily life". Based on the notion that mindfulness training strengthens stress resilience, we explored whether facets of trait mindfulness, prior to training intervention, are linked to acute psychosocial stress reactivity and chronic stress load. To assess different mindfulness facets, over 130 participants completed the Five Facet Mindfulness Questionnaire (FFMQ) and the Freiburg Mindfulness Inventory (FMI). For acute stress induction, a standardized psychosocial stress test was conducted. Subjective stress, sympathetic and parasympathetic activity, and levels of the hypothalamic-pituitary-adrenal axis end hormone cortisol were assessed repeatedly. Additionally, levels of hair cortisol and cortisone as indices of the long-term physiological stress load were collected. We found differential associations of different facets of mindfulness with subjective stress, cortisol, and hair cortisone levels. Specifically, the trait mindfulness facets FMI "Acceptance" and the ability to put one's inner experience into words (FFMQ "Describing") were associated with lower acute subjective and cortisol stress reactivity. Contrarily, monitoring-related trait mindfulness facets (FFMQ "Acting with Awareness" and "Observing") were associated with higher acute cortisol and marginally higher long-term cortisone release. Our results suggest granularity of the mindfulness construct. In accordance with the "Monitor and Acceptance Theory", especially acceptance-related traits buffered against stress, while monitoring-related traits seemed to be maladaptive in the context of stress. The current results give valuable guidance for the conceptualization of mindfulness-based interventions geared towards stress reduction.

Predictors of stress resilience in Parkinson's disease and associations with symptom progression.

People with Parkinson's disease (PD) are sensitive to effects of long-term stress, but might differ in stress resilience, i.e. the ability to maintain mental health despite adversity. It is unclear whether stress resilience in PD is predominantly determined by dopamine deficiency, psychosocial factors, or both. In PD animal models, chronic stressors accelerate disease progression, but evidence in humans is lacking. Our objectives were to (1) distinguish stressor-reactive from resilient PD patients, (2) identify resilience factors, and (3) compare symptom progression between stressor-reactive and resilient patients. We conducted a longitudinal survey in Personalized Parkinson Project participants (N = 350 PD). We used the COVID-19 pandemic as a model of a stressor, aligned in time for the entire cohort. COVID-19-related stressors, perceived stress, and PD symptoms were assessed at 11 timepoints (April-October 2020). Both pre-COVID and in-COVID clinical assessments were available. We quantified stressor-reactivity as the residual between actual and predicted perceived stress relative to COVID-19-related stressors, and modeled trajectories of stressor-reactivity across timepoints. We explored pre-COVID predictors of 6-month average stressor-reactivity, and tested whether stressor-reactivity was prospectively associated with one-year clinical progression rates. Latent class trajectory models distinguished patients with high (N = 123) or low (N = 227) stressor-reactivity. Pre-existing anxiety, rumination and non-motor symptom severity predicted high stressor-reactivity (risk factors), whereas quality of life, social support, positive appraisal style and cognitive abilities predicted low stressor-reactivity (resilience factors). PD-specific factors, e.g. disease duration, motor severity, and levodopa use, did not predict stressor-reactivity. The COVID-19 pandemic did not accelerate disease progression, but worsened depressive symptoms in stressor-reactive PD patients.

Psychological Resilience Factors and Their Association With Weekly Stressor Reactivity During the COVID-19 Outbreak in Europe: Prospective Longitudinal Study.

BACKGROUND: Cross-sectional relationships between psychosocial resilience factors (RFs) and resilience, operationalized as the outcome of low mental health reactivity to stressor exposure (low "stressor reactivity" [SR]), were reported during the first wave of the COVID-19 pandemic in 2020. OBJECTIVE: Extending these findings, we here examined prospective relationships and weekly dynamics between the same RFs and SR in a longitudinal sample during the aftermath of the first wave in several European countries. METHODS: Over 5 weeks of app-based assessments, participants reported weekly stressor exposure, mental health problems, RFs, and demographic data in 1 of 6 different languages. As (partly) preregistered, hypotheses were tested cross-sectionally at baseline (N=558), and longitudinally (n=200), using mixed effects models and mediation analyses. RESULTS: RFs at baseline, including positive appraisal style (PAS), optimism (OPT), general self-efficacy (GSE), perceived good stress recovery (REC), and perceived social support (PSS), were negatively associated with SR scores, not only cross-sectionally (baseline SR scores; all P<.001) but also prospectively (average SR scores across subsequent weeks; positive appraisal (PA), P=.008; OPT, P<.001; GSE, P=.01; REC, P<.001; and PSS, P=.002). In both associations, PAS mediated the effects of PSS on SR (cross-sectionally: 95% CI -0.064 to -0.013; prospectively: 95% CI -0.074 to -0.0008). In the analyses of weekly RF-SR dynamics, the RFs PA of stressors generally and specifically related to the COVID-19 pandemic, and GSE were negatively associated with SR in a contemporaneous fashion (PA, P<.001; PAC,P=.03; and GSE, P<.001), but not in a lagged fashion (PA, P=.36; PAC, P=.52; and GSE, P=.06). CONCLUSIONS: We identified psychological RFs that prospectively predict resilience and cofluctuate with weekly SR within individuals. These prospective results endorse that the previously reported RF-SR associations do not exclusively reflect mood congruency or other temporal bias effects. We further confirm the important role of PA in resilience.

Enhancing precision in human neuroscience.

Human neuroscience has always been pushing the boundary of what is measurable. During the last decade, concerns about statistical power and replicability - in science in general, but also specifically in human neuroscience - have fueled an extensive debate. One important insight from this discourse is the need for larger samples, which naturally increases statistical power. An alternative is to increase the precision of measurements, which is the focus of this review. This option is often overlooked, even though statistical power benefits from increasing precision as much as from increasing sample size. Nonetheless, precision has always been at the heart of good scientific practice in human neuroscience, with researchers relying on lab traditions or rules of thumb to ensure sufficient precision for their studies. In this review, we encourage a more systematic approach to precision. We start by introducing measurement precision and its importance for well-powered studies in human neuroscience. Then, determinants for precision in a range of neuroscientific methods (MRI, M/EEG, EDA, Eye-Tracking, and Endocrinology) are elaborated. We end by discussing how a more systematic evaluation of precision and the application of respective insights can lead to an increase in reproducibility in human neuroscience.

Dynamic Modelling of Mental Resilience in Young Adults: Protocol for a Longitudinal Observational Study (DynaM-OBS).

BACKGROUND: Stress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychological resilience in healthy but susceptible young adults over 9 months. Resilience is conceptualized in this study as the maintenance of mental health or quick recovery from mental health perturbations upon exposure to stressors, assessed longitudinally via frequent monitoring of stressors and mental health. OBJECTIVE: This study aims to investigate the factors predicting mental resilience and adaptive processes and mechanisms contributing to mental resilience and to provide a methodological and evidence-based framework for later intervention studies. METHODS: In a multicenter setting, across 5 research sites, a sample with a total target size of 250 young male and female adults was assessed longitudinally over 9 months. Participants were included if they reported at least 3 past stressful life events and an elevated level of (internalizing) mental health problems but were not presently affected by any mental disorder other than mild depression. At baseline, sociodemographic, psychological, neuropsychological, structural, and functional brain imaging; salivary cortisol and α-amylase levels; and cardiovascular data were acquired. In a 6-month longitudinal phase 1, stressor exposure, mental health problems, and perceived positive appraisal were monitored biweekly in a web-based environment, while ecological momentary assessments and ecological physiological assessments took place once per month for 1 week, using mobile phones and wristbands. In a subsequent 3-month longitudinal phase 2, web-based monitoring was reduced to once a month, and psychological resilience and risk factors were assessed again at the end of the 9-month period. In addition, samples for genetic, epigenetic, and microbiome analyses were collected at baseline and at months 3 and 6. As an approximation of resilience, an individual stressor reactivity score will be calculated. Using regularized regression methods, network modeling, ordinary differential equations, landmarking methods, and neural net-based methods for imputation and dimension reduction, we will identify the predictors and mechanisms of stressor reactivity and thus be able to identify resilience factors and mechanisms that facilitate adaptation to stressors. RESULTS: Participant inclusion began in October 2020, and data acquisition was completed in June 2022. A total of 249 participants were assessed at baseline, 209 finished longitudinal phase 1, and 153 finished longitudinal phase 2. CONCLUSIONS: The Dynamic Modelling of Resilience-Observational Study provides a methodological framework and data set to identify predictors and mechanisms of mental resilience, which are intended to serve as an empirical foundation for future intervention studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39817.

Deep learning and differential equations for modeling changes in individual-level latent dynamics between observation periods.

When modeling longitudinal biomedical data, often dimensionality reduction as well as dynamic modeling in the resulting latent representation is needed. This can be achieved by artificial neural networks for dimension reduction and differential equations for dynamic modeling of individual-level trajectories. However, such approaches so far assume that parameters of individual-level dynamics are constant throughout the observation period. Motivated by an application from psychological resilience research, we propose an extension where different sets of differential equation parameters are allowed for observation subperiods. Still, estimation for intra-individual subperiods is coupled for being able to fit the model also with a relatively small dataset. We subsequently derive prediction targets from individual dynamic models of resilience in the application. These serve as outcomes for predicting resilience from characteristics of individuals, measured at baseline and a follow-up time point, and selecting a small set of important predictors. Our approach is seen to successfully identify individual-level parameters of dynamic models that allow to stably select predictors, that is, resilience factors. Furthermore, we can identify those characteristics of individuals that are the most promising for updates at follow-up, which might inform future study design. This underlines the usefulness of our proposed deep dynamic modeling approach with changes in parameters between observation subperiods.

Revisiting the stress recovery hypothesis: Differential associations of cortisol stress reactivity and recovery after acute psychosocial stress with markers of long-term stress and health.

Exposure to excessive and long-term stress may result in dysregulation of the stress system, including the acute stress response. In particular, failure to downregulate stress-related reactivity may lead to prolonged stress responses and the accumulation of allostatic load. However, the contribution of altered acute cortisol recovery to chronic stress and associated health impairments has often been neglected. Addressing this lack of research, we explored whether recovery from - more so than reactivity to - acute stress captures the basal stress load of an individual. Using Piecewise Growth Curve Models with Landmark Registration, we analyzed cortisol reactivity and recovery slopes of 130 healthy participants exposed to a standardized psychosocial laboratory stressor. Reactivity and recovery were predicted by measures indicative of long-term stress and its downstream effects, including self-report questionnaires, diurnal cortisol indices [cortisol awakening response (CAR); diurnal cortisol slope], markers of pro-inflammatory activity (interleukin-6; high-sensitive C-reactive protein), and hippocampal volume (HCV). Among these measures, only an increased CAR was specifically and consistently associated with relatively impaired recovery. Since the CAR represents the physiological enhancement needed to meet the anticipated demands of the forthcoming day, this finding may highlight the contribution of cognitive processes in determining both CAR and acute stress recovery. Furthermore, greater cortisol reactivity covaried with smaller HCV, showing that increased acute reactivity translates to health-relevant downstream effects. The lack of further associations between long-term and acute stress measures may arise from biases in self-reported chronic stress and the rigorously health-screened study sample. Overall, our findings suggest that while cortisol stress recovery might not supersede reactivity as an indicator of the long-term stress load or associated health effects, recovery and reactivity have differential utility in describing individuals' allostatic states.

Association of polygenic risk scores and hair cortisol with mental health trajectories during COVID lockdown.

The COVID-19 pandemic is a global stressor with inter-individually differing influences on mental health trajectories. Polygenic Risk Scores (PRSs) for psychiatric phenotypes are associated with individual mental health predispositions. Elevated hair cortisol concentrations (HCC) and high PRSs are related to negative mental health outcomes. We analyzed whether PRSs and HCC are related to different mental health trajectories during the first COVID lockdown in Germany. Among 523 participants selected from the longitudinal resilience assessment study (LORA), we previously reported three subgroups (acute dysfunction, delayed dysfunction, resilient) based on weekly mental health (GHQ-28) assessment during COVID lockdown. DNA from blood was collected at the baseline of the original LORA study (n = 364) and used to calculate the PRSs of 12 different psychopathological phenotypes. An explorative bifactor model with Schmid-Leiman transformation was calculated to extract a general genetic factor for psychiatric disorders. Hair samples were collected quarterly prior to the pandemic for determining HCC (n = 192). Bivariate logistic regressions were performed to test the associations of HCC and the PRS factors with the reported trajectories. The bifactor model revealed 1 general factor and 4 sub-factors. Results indicate a significant association between increased values on the general risk factor and the allocation to the acute dysfunction class. The same was found for elevated HCC and the exploratorily tested sub-factor "childhood-onset neurodevelopmental disorders". Genetic risk and long-term cortisol secretion as a potential indicator of stress, indicated by PRSs and HCC, respectively, predicted different mental health trajectories. Results indicate a potential for future studies on risk prediction.

Open and reproducible science practices in psychoneuroendocrinology: Opportunities to foster scientific progress.

This perspective article was written by invitation of the editors in chief as a summary and extension of the symposium entitled Psychoneuroendocrine Research in the Era of the Replication Crisis which was held at the virtual meeting of the International Society of Psychoneuroendocrinology 2021. It highlights the opportunities presented by the application of open and reproducible scientific practices in psychoneuroendocrinology (PNE), an interdisciplinary field at the intersection of psychology, endocrinology, immunology, neurology, and psychiatry. It conveys an introduction to the topics preregistration, registered reports, quantifying the impact of equally-well justifiable analysis decisions, and open data and scripts, while emphasizing 'selfish' reasons to adopt such practices as individual researcher. Complementary to the call for adoption of open science practices, we highlight the need for methodological best practice guidelines in the field of PNE, which could further contribute to enhancing replicability of results. We propose concrete steps for future actions and provide links to additional resources for those interested in adopting open and reproducible science practices in future studies.

A cross-modal component of alexithymia and its relationship with performance in a social cognition task battery.

BACKGROUND: The personality trait alexithymia describes an altered emotional awareness that is associated with a range of social impairments and constitutes a transdiagnostic risk factor for various psychopathologies. Despite the characteristic interoceptive deficits in alexithymia, it is predominantly assessed via self-reports. This can result in unreliable measurements and arguably contributes to the prevailing uncertainty regarding its components, including constricted imaginal processes and emotional reactivity. METHODS: The current study employed an interview and two validated questionnaires to derive a shared component of multi-modally assessed alexithymia in a German non-clinical sample (n = 78) via prinicipal component analysis. This component was used as a predictor for performance in four behavioural social cognition tasks. The relative importance of this predictor against related variables was assessed via dominance analysis. RESULTS: The identified component reflected cognitive alexithymia. Higher cognitive alexithymia scores were associated with less affective distress in an ostracizing task. Dominance analysis revealed the dominance of competing autism traits relative to cognitive alexithymia and competing predictors empathy, depression, and anxiety, in predicting affective distress. LIMITATIONS: Emotional reactivity was only assessed via self-report and no implicit measures of alexithymia were employed. Due to the low reliability of the self-report measure, no measure of emotional reactivity could be included in the principal component analysis. CONCLUSIONS: Our results provide compelling evidence that cognitive interoceptive deficits are at the core of alexithymia across assessment modalities. Behavioural data suggest that these deficits result in diminished emotional sensitivity to high-pressure social situations, which may cause a lack of behavioural adaptation.

Contemplative Mental Training Reduces Hair Glucocorticoid Levels in a Randomized Clinical Trial.

OBJECTIVE: This study aimed to investigate the effect of regular contemplative mental training on endocrine and psychological indices of long-term stress. METHODS: An open-label efficacy trial that comprised three distinct 3-month long modules targeting attention and interoception, socioaffective, or sociocognitive abilities through dyadic exercises and secularized meditation practices was conducted with healthy adults. Participants underwent the training for 3 or 9 months, or were assigned to a retest control cohort. Chronic stress indices were assayed at four time points: pretraining and after 3, 6, and 9 months. The main outcome measures were cortisol (HC) and cortisone (HE) concentration in hair and self-reported long-term stress. RESULTS: Of 362 initially randomized individuals, 30 dropped out before study initiation (n = 332; mean [SD] age = 40.7 [9.2] years; 197 women). Hair-based glucocorticoid assays were available from n = 227, and questionnaire data from n = 326. Results from three separate training cohorts (TC1-3) revealed consistent decreases in HC and HE levels over the first three (TC3) to 6 months (TC1 and TC2) of training, with no further reduction at the final 9-month mark (baseline to end of training differences, HC, TC1: t(355) = 2.59, p = .010, contrast estimate (est.) [SE] = 0.35 [0.14]; HC, TC2: t(363) = 4.06, p < .001, est. = 0.48 [0.12]; HC, TC3: t(368) = 3.18, p = .002, est. = 0.41 [0.13]; HE, TC1: t(435) = 3.23, p = .001, est. = 0.45 [0.14]; HE, TC2: t(442) = 2.60, p = .010, est. = 0.33 [0.13]; HE, TC3: t(446) = 4.18, p < .001, est. = 0.57 [0.14]). Training effects on HC increased with individual compliance (practice frequency), and effects on both HC and HE were independent of training content and unrelated to change in self-reported chronic stress. Self-reported stress, and cortisol-to-dehydroepiandrosterone ratios as an exploratory endpoint, were also reduced, albeit less consistently. CONCLUSIONS: Our results point to the reduction of long-term cortisol exposure as a mechanism through which meditation-based mental training may exert positive effects on practitioners' health.Trial Registration: ClinicalTrials.gov identifier: NCT01833104.

Psycho-social factors associated with mental resilience in the Corona lockdown.

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics.

Only vulnerable adults show change in chronic low-grade inflammation after contemplative mental training: evidence from a randomized clinical trial.

Growing evidence suggests that chronic low-grade inflammation can be reduced through mindfulness-based mental training interventions. However, these results are inconsistent and based on patient populations with heterogeneous conditions. Similar research in healthy adults is lacking. Moreover, common intervention protocols involve varying combinations of different contemplative practices, such that it remains unclear which types of training most effectively influence biomarkers of inflammation. The present study investigated the effect of three distinct 3-month training modules cultivating a) interoception and present-moment focus (Presence), b) socio-affective skills (Affect), or c) socio-cognitive skills (Perspective) on the inflammatory biomarkers interleukin-6 (IL-6) and high sensitive C-reactive protein (hs-CRP) in 298 healthy adults. We observed no group-level effect of training on either biomarker, but trend-level interactions of training type and participant sex. In additionally exploring the influence of participants' baseline inflammation, a selective training effect emerged: Following the Presence module, participants with relatively higher inflammatory load showed stronger reduction in IL-6 on average, and in hs-CRP if they were male. Mindfulness- and attention-based mental practice thus appears most effective when targeting chronic low-grade inflammation in healthy adults, particularly in men. Overall, our data point to a floor effect in the reduction of inflammatory markers through contemplative mental training, suggesting that mental training may be less effective in improving basal biological health outcomes in healthy, low-stressed adults than in vulnerable populations.

Association of Short-term Change in Leukocyte Telomere Length With Cortical Thickness and Outcomes of Mental Training Among Healthy Adults: A Randomized Clinical Trial.

Importance: Telomere length is associated with the development of age-related diseases and structural differences in multiple brain regions. It remains unclear, however, whether change in telomere length is linked to brain structure change, and to what extent telomere length can be influenced through mental training. Objectives: To assess the dynamic associations between leukocyte telomere length (LTL) and cortical thickness (CT), and to determine whether LTL is affected by a longitudinal contemplative mental training intervention. Design, Setting, and Participants: An open-label efficacy trial of three 3-month mental training modules with healthy, meditation-naive adults was conducted. Data on LTL and CT were collected 4 times over 9 months between April 22, 2013, and March 31, 2015, as part of the ReSource Project. Data analysis was performed between September 23, 2016, and June 21, 2019. Of 1582 eligible individuals, 943 declined to participate; 362 were randomly selected for participation and assigned to training or retest control cohorts, with demographic characteristics matched. The retest control cohorts underwent all testing but no training. Intention-to-treat analysis was performed. Interventions: Training cohort participants completed 3 modules cultivating interoception and attention (Presence), compassion (Affect), or perspective taking (Perspective). Main Outcomes and Measures: Change in LTL and CT. Results: Of the 362 individuals randomized, 30 participants dropped out before study initiation (initial sample, 332). Data were available for analysis of the training intervention in 298 participants (n = 222 training; n = 76 retest control) (175 women [58.7%]; mean [SD] age, 40.5 [9.3] years). The training modules had no effect on LTL. In 699 observations from all 298 participants, mean estimated changes in the relative ratios of telomere repeat copy number to single-copy gene (T/S) were for no training, 0.004 (95% CI, -0.010 to 0.018); Presence, -0.007 (95% CI, -0.025 to 0.011); Affect, -0.005 (95% CI, -0.019 to 0.010); and Perspective, -0.001 (95% CI, -0.017 to 0.016). Cortical thickness change data were analyzed in 167 observations from 67 retest control participants (37 women [55.2%], mean [SD] age, 39.6 [9.0] years). In this retest control cohort subsample, naturally occurring LTL change was related to CT change in the left precuneus extending to the posterior cingulate cortex (mean t161 = 3.22; P < .001; r = 0.246). At the individual participant level, leukocyte telomere shortening as well as lengthening were observed. Leukocyte telomere shortening was related to cortical thinning (t77 = 2.38; P = .01; r = 0.262), and leukocyte telomere lengthening was related to cortical thickening (t77 = 2.42; P = .009; r = 0.266). All analyses controlled for age, sex, and body mass index. Conclusions and Relevance: The findings of this trial indicate an association between short-term change in LTL and concomitant change in plasticity of the left precuneus extending to the posterior cingulate cortex. This result contributes to the evidence that LTL changes more dynamically on the individual level than previously thought. Further studies are needed to determine potential long-term implications of such change in relation to cellular aging and the development of neurodegenerative disorders. No effect of contemplative mental training was noted in what may be, to date, the longest intervention with healthy adults. Trial Registration: ClinicalTrials.gov identifier: NCT01833104.

Exploring the multidimensional complex systems structure of the stress response and its relation to health and sleep outcomes.

To gain a comprehensive understanding of the multidimensional complex systems structure of the stress response and related health outcomes, we utilized network analysis in a sample of 328 healthy participants in two steps. In a first step, we focused on associations between measures of basal hypothalamic-pituitary-adrenal axis functioning and subjective stress perceptions. In a second step, we linked these diverse stress-related measures to biomarkers and self-reports of health and sleep. Overall, measures clustered depending on their method of assessment, with high correlations between different saliva-based indices of diurnal cortisol regulation, between cortisol and cortisone levels in hair, between different biological health indicators (systemic inflammatory activity and body mass index), between state (experience sampling) and trait (questionnaire-based) self-reports of stress and wellbeing, and between different self-reports of sleep. Bridges between clusters suggested that if individuals perceive stress throughout their daily lives this is reflected in their total salivary cortisol output possibly contributing to long-term cortisol accumulation in hair. Likewise, earlier awakening time may contribute to cortisol accumulation in hair via an influence on awakening cortisol processes. Our results show that while meaningful connections between measures exist, stress is a highly complex construct composed of numerous aspects. We argue that network analysis is an integrative statistical approach to address the multidimensionality of the stress response and its effects on the brain and body. This may help uncover pathways to stress-related disease and serve to identify starting points for prevention and therapeutic intervention.

Romance, risk, and replication: Can consumer choices and risk-taking be primed by mating motives?

Interventions aimed at influencing spending behavior and risk-taking have considerable practical importance. A number of studies motivated by the costly signaling theory within evolutionary psychology have reported that priming inductions (such as looking at pictures of attractive opposite sex members) designed to trigger mating motives increase males' stated willingness to purchase conspicuous consumption items and to engage in risk-taking behaviors, and reduce loss aversion. However, a meta-analysis of this literature reveals strong evidence of either publication bias or p-hacking (or both). We then report 8 studies with a total sample of over 1,600 participants which sought to reproduce these effects. None of the studies, including one that was fully preregistered, was successful. The results question the claim that romantic primes can influence risk-taking and other potentially harmful behaviors.