Physiological Profiling of Agitation in Dementia: Insights From Wearable Sensor Data.

Background and Objectives: The number of people with dementia is expected to triple to 152 million in 2050, with 90% having accompanying behavioral and psychological symptoms (BPSD). Agitation is among the most critical BPSD and can lead to decreased quality of life for people with dementia and their caregivers. This study aims to explore objective quantification of agitation in people with dementia by analyzing the relationships between physiological and movement data from wearables and observational measures of agitation. Research Design and Methods: The data presented here is from 30 people with dementia, each included for 1 week, collected following our previously published multimodal data collection protocol. This observational protocol has a cross-sectional repeated measures design, encompassing data from both wearable and fixed sensors. Generalized linear mixed models were used to quantify the relationship between data from different wearable sensor modalities and agitation, as well as motor and verbal agitation specifically. Results: Several features from wearable data are significantly associated with agitation, at least the p < .05 level (absolute ß: 0.224-0.753). Additionally, different features are informative depending on the agitation type or the patient the data were collected from. Adding context with key confounding variables (time of day, movement, and temperature) allows for a clearer interpretation of feature differences when a person with dementia is agitated. Discussion and Implications: The features shown to be significantly different, across the study population, suggest possible autonomic nervous system activation when agitated. Differences when splitting the data by agitation type point toward a need for future detection models to tailor to the primary type of agitation expressed. Finally, patient-specific differences in features indicate a need for patient- or group-level model personalization. The findings reported in this study both reinforce and add to the fundamental understanding of and can be used to drive the objective quantification of agitation.

Mild daily stress, in interaction with NR3C1 DNA methylation levels, is linked to alterations in the HPA axis and ANS response to acute stress in early adolescents.

BACKGROUND: Daily Hassles (DH) or daily stress - is a mild type of stressor with unique contributions to psychological distress. Yet, most prior studies that investigate the effects of stressful life experiences focus on childhood trauma or on early life stress and little is known about the effects of DH on epigenetic changes in stress system related genes and on the physiological response to social stressors. METHODS: In the present study, conducted among 101 early adolescents (mean age = 11.61; SD = 0.64), we investigated whether Autonomic Nervous System (ANS) (namely heart rate and heart rate variability) and Hypothalamic-Pituitary-Adrenal (HPA) axis functioning (measured as cortisol stress reactivity and recovery) are associated with DNA methylation (DNAm) in the glucocorticoid receptor gene (NR3C1), the level of DH and their interaction. To assess the stress system functioning the TSST protocol was used. RESULTS: Our findings show that higher NR3C1 DNAm in interaction with higher levels of daily hassles, is associated with blunted HPA axis reactivity to psychosocial stress. In addition, higher levels of DH are associated with extended HPA axis stress recovery. In addition, participants with higher NR3C1 DNAm had lower ANS adaptability to stress, specifically lower parasympathetic withdrawal; for heart rate variability this effect was strongest for participants with higher level of DH. CONCLUSIONS: The observation that interaction effects between NR3C1 DNAm levels and daily stress on the functioning of the stress-systems, are already detectable in young adolescents, highlights the importance of early interventions, not only in the case of trauma, but also daily stress. This might help to prevent stress-induced mental and physical disorders later in life.

Exploring the perception of stress in childhood and early adolescence.

Stressful life experiences may jeopardize the healthy development of children. To improve interventions, more knowledge is needed on the perception of stress by children. In adults, stress is regarded as a state of low valence and high arousal. It is unclear whether children perceive stress similarly. In the current study, 35 children of the general population completed three tasks aiming to provide insight into their knowledge of the concept stress. In the first task, participants were asked about their verbal knowledge of the concept stress. In the second task, they rated the valence and arousal of eight emotion-evoking vignettes. In the final task, participants completed an experience sampling survey for at least 1 day, consisting of a stress thermometer and pictorial scales of valence and arousal. Participants' perception of stress was found to be mainly valence focused. Age and sex were found to play a role in the degree of arousal focus. Older participants differentiated more in arousal levels than younger participants, as did girls in comparison with boys. Because the perception of stress depends on developmental and other individual factors, using stress as a single measurement dimension in a survey is not recommended.

The cumulative effect of chronic stress and depressive symptoms affects heart rate in a working population.

Background: Chronic stress and depressive symptoms have both been linked to increased heart rate (HR) and reduced HR variability. However, up to date, it is not clear whether chronic stress, the mechanisms intrinsic to depression or a combination of both cause these alterations. Subclinical cases may help to answer these questions. In a healthy working population, we aimed to investigate whether the effect of chronic stress on HR circadian rhythm depends on the presence of depressive symptoms and whether chronic stress and depressive symptoms have differential effects on HR reactivity to an acute stressor. Methods: 1,002 individuals of the SWEET study completed baseline questionnaires, including psychological information, and 5 days of electrocardiogram (ECG) measurements. Complete datasets were available for 516 individuals. In addition, a subset (n = 194) of these participants completed a stress task on a mobile device. Participants were grouped according to their scores for the Depression Anxiety Stress Scale (DASS) and Perceived Stress Scale (PSS). We explored the resulting groups for differences in HR circadian rhythm and stress reactivity using linear mixed effect models. Additionally, we explored the effect of stress and depressive symptoms on night-time HR variability [root mean square of successive differences (RMSSD)]. Results: High and extreme stress alone did not alter HR circadian rhythm, apart from a limited increase in basal HR. Yet, if depressive symptoms were present, extreme chronic stress levels did lead to a blunted circadian rhythm and a lower basal HR. Furthermore, blunted stress reactivity was associated with depressive symptoms, but not chronic stress. Night-time RMSSD data was not influenced by chronic stress, depressive symptoms or their interaction. Conclusion: The combination of stress and depressive symptoms, but not chronic stress by itself leads to a blunted HR circadian rhythm. Furthermore, blunted HR reactivity is associated with depressive symptoms and not chronic stress.

Individual differences in environmental sensitivity at physiological and phenotypic level: Two sides of the same coin?

Young adolescents are hypothesized to differ in their environmental sensitivity, at both phenotypic (i.e., Sensory Processing Sensitivity [SPS]) and physiological (i.e., biological stress response) level. This is the first study that investigated whether individual differences in environmental sensitivity at physiological level could be predicted by individual differences at phenotypic level, as measured with the HSC scale. A total of 101 adolescents (Mage = 11.61, SDage = 0.64) participated in a standardized social stress task (i.e., Trier Social Stress Task-Modified version for children and adolescents (TSST-M)). From baseline to the end of recovery, eight cortisol samples were collected, as well as a continuous measure of Autonomic Nervous System activity. Adolescents reported on SPS and on perceived stress before, during, and after TSST-M. As a follow-up analysis, the quality of the environment, the possible overlap with Neuroticism, and several covariates were considered. Multilevel models were used to investigate within- and between-person differences in stress reactivity across different systems. Results indicate significant individual differences in heart rate, heart rate variability, skin conductance, cortisol, and perceived stress in response to the TSST-M. Only for perceived stress significant differences in SPS were observed, with more sensitive individuals perceiving more negative and less positive affect. For environmental quality and the interaction between SPS and Neuroticism results showed higher recovery rates of heart rate in high quality environments and stronger cortisol responses for adolescents scoring high on both SPS and Neuroticism. Potential explanations for these findings and implications for current theorizing on environmental sensitivity are discussed.

Twenty-Four-Hour Heart Rate Is a Trait but Not State Marker for Depression in a Pilot Randomized Controlled Trial With a Single Infusion of Ketamine.

Background: Abnormalities of heart rate (HR) and its variability are characteristic of major depressive disorder (MDD). However, circadian rhythm is rarely taken into account when statistically exploring state or trait markers for depression. Methods: A 4-day electrocardiogram was recorded for 16 treatment-resistant patients with MDD and 16 age- and sex-matched controls before, and for the patient group only, after a single treatment with the rapid-acting antidepressant ketamine or placebo (clinical trial registration available on https://www.clinicaltrialsregister.eu/ with EUDRACT number 2016-001715-21). Circadian rhythm differences of HR and the root mean square of successive differences (RMSSD) were compared between groups and were explored for classification purposes. Baseline HR/RMSSD were tested as predictors for treatment response, and physiological measures were assessed as state markers. Results: Patients showed higher HR and lower RMSSD alongside marked reductions in HR amplitude and RMSSD variation throughout the day. Excellent classification accuracy was achieved using HR during the night, particularly between 2 and 3 a.m. (90.6%). A positive association between baseline HR and treatment response (r = 0.55, p = 0.046) pointed toward better treatment outcome in patients with higher HR. Heart rate also decreased significantly following treatment but was not associated with improved mood after a single infusion of ketamine. Limitations: Our study had a limited sample size, and patients were treated with concomitant antidepressant medication. Conclusion: Patients with depression show a markedly reduced amplitude for HR and dysregulated RMSSD fluctuation. Higher HR and lower RMSSD in depression remain intact throughout a 24-h day, with the highest classification accuracy during the night. Baseline HR levels show potential for treatment response prediction but did not show potential as state markers in this study. Clinical trial registration: EUDRACT number 2016-001715-21.

Gastrointestinal symptoms in office workers are predicted by psychological distress and short sleep duration.

OBJECTIVE: Gastrointestinal (GI) symptoms can be triggered by several lifestyle factors, including psychological distress, short sleep duration, and diet. It is poorly known which physiological mechanisms are involved, but the autonomic nervous system (as a key mediator of the stress response) is a likely candidate. We aimed to investigate the associations between selected lifestyle factors, measures of stress physiology, and GI symptoms. METHODS: This is a longitudinal study of 1002 office employees (52% male, mean age 39 ± 10 years), who were asked to report their GI symptoms, psychological distress, sleep times, and intake of caffeine, alcohol, and soft drinks for 5 days. Skin conductance, heart rate / variability, and acceleration were automatically recorded using wearable sensors. 850 participants from this study were eligible for analysis. We computed within-person correlations between the variables and used mediation analysis to test causal models. RESULTS: Sleep duration (ρ = -0.12, p < 0.001) and psychological distress (ρ = 0.19, p < 0.001) were significantly though weakly associated with GI symptoms. The physiological variables were not or weakly associated with GI symptoms in this study. The association between sleep duration and GI symptoms was largely mediated by psychological distress (61%). CONCLUSIONS: Short sleep and psychological distress predict GI symptoms in office workers. Further research is needed to unravel the physiological mechanisms mediate this association.

Relationship Between Chronic Stress and Heart Rate Over Time Modulated by Gender in a Cohort of Office Workers: Cross-Sectional Study Using Wearable Technologies.

BACKGROUND: Chronic stress is increasing in prevalence and is associated with several physical and mental disorders. Although it is proven that acute stress changes physiology, much less is known about the relationship between physiology and long-term stress. Continuous measurement of vital signs in daily life and chronic stress detection algorithms could serve this purpose. For this, it is paramount to model the effects of chronic stress on human physiology and include other cofounders, such as demographics, enabling the enrichment of a population-wide approach with individual variations. OBJECTIVE: The main objectives of this study were to investigate the effect of chronic stress on heart rate (HR) over time while correcting for weekdays versus weekends and to test a possible modulation effect by gender and age in a healthy cohort. METHODS: Throughout 2016 and 2017, healthy employees of technology companies were asked to participate in a 5-day observation stress study. They were required to wear two wearables, of which one included an electrocardiogram sensor. The derived HR was averaged per hour and served as an output for a mixed design model including a trigonometric fit over time with four harmonics (periods of 24, 12, 8, and 6 hours), gender, age, whether it was a workday or weekend day, and a chronic stress score derived from the Perceived Stress Scale (PSS) as predictors. RESULTS: The study included 328 subjects, of which 142 were female and 186 were male participants, with a mean age of 38.9 (SD 10.2) years and a mean PSS score of 13.7 (SD 6.0). As main effects, gender (χ21=24.02, P<.001); the hour of the day (χ21=73.22, P<.001); the circadian harmonic (χ22=284.4, P<.001); and the harmonic over 12 hours (χ22=242.1, P<.001), over 8 hours (χ22=23.78, P<.001), and over 6 hours (χ22=82.96, P<.001) had a significant effect on HR. Two three-way interaction effects were found. The interaction of age, whether it was a workday or weekend day, and the circadian harmonic over time were significantly correlated with HR (χ22=7.13, P=.03), as well as the interaction of gender, PSS score, and the circadian harmonic over time (χ22=7.59, P=.02). CONCLUSIONS: The results show a relationship between HR and the three-way interaction of chronic stress, gender, and the circadian harmonic. The modulation by gender might be related to evolution-based energy utilization strategies, as suggested in related literature studies. More research, including daily cortisol assessment, longer recordings, and a wider population, should be performed to confirm this interpretation. This would enable the development of more complete and personalized models of chronic stress.