The influence of everyday emotions on mucosal immunity: An intensive longitudinal modeling approach.

Mucosal immunity is a multifaceted system of immunological responses that provides a barrier against pathogenic invasion and can be regulated by psychosocial and neuroendocrine factors. The present study aims to elucidate the association between everyday emotional states, emotion regulation skills, and mucosal immunity by utilizing an ambulatory assessment approach. 30 healthy subjects (61% male; M = 30.18 years old) completed an emotion questionnaire (PANAS) and collected saliva samples via passive drool to determine salivary immunoglobulin-A (S-IgA) excretion rate three times a day over a period of 1 week. In a multi-level model, the influence of emotions on S-IgA, both on a within-subject and between-subject level, was estimated. We found that most of the variation in S-IgA (74%) was accounted for by within-subject changes rather than stable between-subject differences. On a within-subject level, negative emotions had a significant positive effect on S-IgA levels (b = 1.87, p = .015), while positive emotions had no effect. This effect of negative emotions was moderated by the individual emotion regulation skills, with higher regulation skills corresponding to smaller effects (b = -2.67, p = .046). Furthermore, S-IgA levels decreased over the course of a day, indicating circadian rhythmicity (b = -0.13, p = .034). These results highlight the possibilities of intensive longitudinal data to investigate the covariance between psychological and immunological states over time.

Personalized therapy in rheumatoid arthritis (PETRA): a protocol for a randomized controlled trial to test the effect of a psychological intervention in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects cartilage and bone. Psychological stress can both trigger disease exacerbation and result from disease activity. As standard pharmacological interventions alone have limited success in treating RA, a more comprehensive biopsychosocial approach to treatment has been recommended. In this prospective randomized controlled trial (RCT), a psychotherapeutically guided, group-based intervention program will be conducted with RA patients over a period of 9 months. This program combines a dynamic-interactional model with disorder-specific coping-oriented perspectives to improve patients' social, emotional, and problem-solving competencies as well as stress system functional status. The enrolment of 440 patients, randomly allocated to either an intervention (n = 220) or control group (n = 220), is planned. To evaluate the intervention effect, various indicators of RA disease activity, stress system activity, and psychological condition will be assessed through sets of standardized questionnaires and biochemical analyses of blood and saliva samples. Moreover, healthcare-related costs for each patient will be obtained using routine health insurance data. Outcome variables will be measured in all patients at regular intervals prior to intervention (baseline), during the 9-month intervention (five time points), and during a 9-month follow-up phase (three time points), allowing the comprehensive analysis of within- and between-subject effects, i.e. trajectories of the target variables in the intervention and control groups. In addition, to investigate the intervention effects on real-life stress system functioning in RA, 10 integrative single-case studies (n = 5 from the intervention group, n = 5 from the control group) will be conducted. In each study, once before and after the 9-month intervention, urine samples will be collected, and patients will fill out questionnaires for approximately 1 month at 12-h intervals. Moreover, weekly in-depth interviews will be conducted with patients to determine their previous week's emotionally positive and negative incidents. Using time series analysis, it is then possible to investigate whether and how stress system function in these RA patients has improved from the applied intervention. By using both an investigational macro- and microperspective, this project aims to evaluate a psychological intervention in the routine care of individuals with RA.Trial registration German Clinical Trials Register DRKS00028144. Registered on 1 March 2022.

Emotional states predict cellular immune system activity under conditions of life as it is lived: A multivariate time-series analysis approach.

The relationship between emotional states and immune system activity is characterized by bidirectional influences; however, limited information is available regarding the temporal dynamics of these effects. The goal of this investigation was to examine how these psychoimmunological interdependencies unfold over time under conditions of "life as it is lived". For this purpose, three healthy women collected their entire urine over a period of approximately two months at 12-h intervals (8 am-8 pm, 8 pm-8 am), resulting in a total of 112 to 126 consecutive measurements per subject. In addition, among other regular psychological assessments, the subjects completed the EWL-60-S, an emotional state questionnaire, each morning and evening. To assess the extent of T-helper type 1 immune activation, the neopterin per creatinine concentration was measured in the urine samples using high-pressure liquid chromatography. The dynamic relationships between the time series of the six emotional states (performance-related activity, general inactivity, extraversion/introversion, general feeling of comfort, emotional irritation, anxiety/depressiveness) and urinary neopterin levels were estimated in vector-autoregressive models and evaluated using Granger-causality tests, impulse-response functions and forecast error variance decompositions. The findings showed that emotional states explained up to 20% of the variance of urinary neopterin per creatinine levels, whereby most of the effects occurred within a period of approximately three days. Across all subjects, increases in anxiety/depressiveness and extraversion led to increases in neopterin levels, while a general feeling of comfort led to decreases in neopterin. These results emphasize the importance of the interdependencies between emotional states and immune system activity and showcase the potential that intensive longitudinal study designs offer for psychoneuroimmunology.

On the Role of Psychoneuroimmunology in Oral Medicine.

Psychoneuroimmunology (PNI) is an area of interdisciplinary research exploring the complex interactions within the immuno-neuro-endocrine system in response to psychosocial influences. Such influences can trigger neurological changes, leading to immunological effects related to the emergence and course of various diseases. This concise clinical review explores the role of PNI in oral medicine in three exemplary models of oral disease: periodontitis, herpes labialis, and oral lichen planus. Previous literature has shown that psychosocial stress is related to exacerbations in these three oral diseases and to poorer overall oral health. The presumed biological mechanisms affect the activity of stress axes, i.e. the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), and subsequent immune system dysregulation. Although these PNI mechanisms remain poorly understood, several stress reduction interventions in clinical oral medicine have already yielded promising results. In future work, the elucidation of pathways within PNI networks will require carefully designed studies with sensitive methodology, e.g. the integrative single-case design. A biopsychosocial approach has the potential to move disease models in oral medicine from simple connections rooted in empirical dualism and reductionism to the establishment of network-based models. Further research on these complex connections should lead to novel clinical approaches and preventive strategies in oral medicine.

About-Weekly Pattern in the Dynamic Complexity of a Healthy Subject's Cellular Immune Activity: A Biopsychosocial Analysis.

In a previous integrative single-case study, we collected biological, psychological and social time-series data on a 25-year-old healthy woman over the course of 126 12-h intervals (63 days) and used urinary neopterin as an indicator of cellular immune activity [Schubert et al. 2012 (1)]. The present re-evaluation introduced Dynamic Complexity (DC) as an additional non-linear and non-stationary measure to further investigate the subject's biopsychosocial dynamics during the study. The new time series dealing with urinary neopterin complexity revealed a cyclic, circaseptan (about-weekly) repeating pattern (6.59 days). The only weekly reoccurring events over the course of the study that were associated with this immunological pattern were the in-depth interviews with the subject (mean distance between interviews: 6.5 days). Superposed epoch analysis (SEA) revealed a U-shaped relation between neopterin complexity and interviews, with a decrease in neopterin complexity before and during interviews and an increase after interviews. Furthermore, the complexity scores for irritation, anxiousness/depressiveness and mental activity were positively correlated with neopterin complexity. The results suggest that the interviews, which had been found to be related to the subject's need for educational and/or social accomplishment, were marked by stress (decrease in psycho-immunological flexibility and adaptability), which was then relieved after the interviews (increase in psycho-immunological flexibility and adaptability). It appears that the subject's cellular immune activity, as indicated by neopterin complexity, functionally mirrored the emotional meaning she ascribed to the in-depth interviews. This re-evaluation is in line with the view that biopsychosocial research requires multimodal analysis of single cases based on qualitative (e.g., in-depth interviews) and quantitative (e.g., time series analysis) data under conditions of "life as it is lived".