Once thought of as an immune-privileged site, we now know that the nervous system communicates in a bidirectional manner with the immune system via the neuroimmune axis. Neuropeptides constitute a component of this axis, playing critical roles in the brain and periphery. The function of salivary neuropeptides in the acute stress response is not well understood. The purpose of this study is to investigate salivary neuropeptide levels during acute stress. Salivary samples were collected from fire recruits engaged in a stress training exercise previously shown to induce acute stress, at three separate timepoints during the exercise and levels of oxytocin, neurotensin, Substance P, α-MSH, and β-Endorphin were measured using the Human Neuropeptide 5-Plex Custom Assay Eve Technologies. All neuropeptides increased throughout the acute stress simulation and during the recovery phase. Exploratory factor analysis (EFA) identified one factor contributing to baseline values across five neuropeptides and Pairwise Pearson Correlation Coefficient analysis showed positive correlations >0.9 for almost all neuropeptide combinations at the pre-stress timepoint. Further analysis identified negative and positive correlations between past-life trauma and self-assessed hardiness, respectively. Calculated neuropeptide scores showed an overall positive correlation to self-assessed hardiness. Altogether, our results suggest that salivary neuropeptides increase synchronously during acute stress and higher levels correlate with an increase in self-assessed hardiness. Further study is required to determine if interventions designed to enhance neuropeptide activity can increase stress resilience, especially in high-stress occupations such as firefighting.

Background/Objectives: This pilot study aimed to investigate the relationship between salivary neuropeptides levels, adverse childhood experiences (ACEs), and altruism in a sample of medical students. Additionally, the study examined potential sex differences in these relationships. Methods: Sixty medical students (36.6% men, 63.3% women) provided saliva samples to measure oxytocin, α-MSH, β-endorphin, neurotensin, and substance P using a custom 5-plex human peptide assay. Participants completed the ACE Survey and Compassionate Love Scale for Humanity (CLS-H) Altruism Survey. Descriptive statistics characterized demographics and survey data, with out-of-range values adjusted to the standard curve maximum. Data normality was assessed with the Jarque–Bera test; due to non-normality, values were log-transformed. Differences between male and female salivary, ACE score, and CLS-H altruism score were tested using t-tests and Mann–Whitney U-tests, while correlations were evaluated with Pearson and Spearman coefficients. Results: The five neuropeptides, while highly correlated with each other, did not exhibit significant relationships with altruism, as measured by the CLS-H Altruism Survey. Finally, female participants demonstrated greater altruistic tendencies compared with male participants with marginal significance. Conclusions: While there were no significant relationships between the fives neuropeptides, ACEs, or altruism; women demonstrated higher levels of altruism compared with men. The data reported in this pilot study did not strongly support the conclusion that neuropeptides influence social behavior and trauma response. Furthermore, future studies with larger, more diverse samples and multiple time point measurements of neuropeptides could be beneficial to better understand the relationships between neuropeptides and any potential implications for mental health interventions.

Chronic psychological stress is known to influence immune function and contribute to development of autoimmune disorders through dysregulated inflammatory responses. This study investigates relationships between acute stress, life trauma, and autoimmune salivary biomarkers in firefighter recruits during psychophysical stress training. Salivary samples were collected from firefighter recruits during two stress tests to evaluate responses to acute stress. Samples were obtained at three time points—pre-stress, post-stress, and recovery—across both tests. Cortisol was measured to characterize acute stress response (ASR) profiles, while immune function was assessed through the analyzing C-reactive Protein (CRP), Complement C4 (C4), Pigment Epithelium Derived Factor (PEDF), and Serum Amyloid P (SAP). Results showed significant changes in CRP, C4, and PEDF after stress inoculation. Higher previous life trauma was associated with lower baseline cortisol (r = −0.489) and delay in cortisol recovery (r = 0.514), suggesting a learned biological response, potentially protective against stress-induced dysregulation. Cluster analysis revealed four distinct cortisol ASR profiles which were found to have significantly different past life trauma (p = 0.031). These findings suggest that trauma history influences stress biomarker dynamics, potentially reflecting individualized adaptive or maladaptive responses. The insights gained may inform strategies to enhance stress resilience and mitigate autoimmune risk among high-stress populations.

Stress is a fundamental physiological and psychological response to environmental challenges, regulated by the interplay between the hypothalamic-pituitary-adrenal (HPA) axis, the autonomic nervous system, and immune-inflammatory pathways. Resilience, the ability to adapt and recover from stress, is increasingly recognized as a key factor in maintaining homeostasis and preventing stress-related pathology. Traditional biomarker assessment methods, such as blood sampling, pose limitations due to their invasiveness and inability to capture real-time physiological changes. Saliva has emerged as an optimal diagnostic fluid due to its non-invasive nature and its capacity to reflect dynamic neuroendocrine and immune responses. This chapter explores the use of salivary neuropeptides, hormones, and cytokines as biomarkers of stress and resilience, detailing their physiological roles and measurement methodologies. Key biomarkers including various hormones, immune modulating neuropeptides along with cytokines and chemokines, are discussed. We discuss their relevance in distinguishing between acute and chronic stress responses and their potential utility in identifying individuals in early stages or at risk for stress-related disorders. Emerging evidence supports the integration of salivary biomarker analysis in clinical and research settings, with advancements in immunoassays and mass spectrometry improving sensitivity and specificity. Future research should focus on systems approaches and long-term biomarker profiling to enhance predictive modeling of stress resilience. The application of salivary biomarkers in stress research holds significant promise for personalized diagnostics and early interventions aimed at mitigating the long-term effects of chronic stress.