Psychosocial stress is a central risk factor for major depressive disorder (MDD) and may represent a key pathway through which genetic liability manifests. While polygenic scores for depression (DEP-PGS) have been linked to neural phenotypes, their association with experimentally induced psychosocial stress responses and stress adaptation dynamics remains unclear.

We investigated associations between DEP-PGS and whole-brain neural responses to acute psychosocial stress in 190 healthy young adults (117 female) using the fMRI-compatible ScanSTRESS paradigm. Whole-brain analyses examined associations between DEP-PGS and stress-related activation, including sex-specific effects. Exploratory analyses further examined associations with current depressive symptom severity. In addition to overall stress reactivity, we tested whether DEP-PGS predicted exposure-time effects, reflecting changes in neural activation across two consecutive stress runs.

Higher DEP-PGS was associated with reduced stress-related activation in striatal regions (ncl. caudatus/ncl. accumbens). A significant sex × DEP-PGS interaction revealed opposite associations in males (positive) and females (negative). Depressive symptom severity was independently linked to increased stress-related activation in the ncl. caudatus and thalamus. Beyond stress magnitude, DEP-PGS was associated with altered exposure-time dynamics across a distributed fronto-cingulo-insular network. In the putamen, higher DEP-PGS predicted increasing activation across runs in females but decreasing activation in males.

Genetic liability for depression is associated not only with altered neural stress reactivity but also with sex-dependent changes in stress adaptation dynamics under repeated psychosocial stress. These findings suggest that depression polygenic risk may manifest in altered temporal regulation of stress-responsive circuits, potentially representing an early neural vulnerability marker.

The stress response is closely linked to energy metabolism, with blood glucose shaping endocrine reactivity. While glucose intake has been shown to increase cortisol reactivity, its effects on neural stress processing and the role of the associated insulin-response are not well characterized. We thus studied the effect of both metabolic markers on the endocrine, cardiovascular, and neural response to psychosocial stress in healthy men and women.

Fifty-four fasted adults (age mean = 22.5, SD = 3.5; 54% women) either consumed glucose (50g; n = 27), or water (n = 27) before being exposed to the Montreal Imaging Stress Task (MIST). Functional near-infrared spectroscopy (fNIRS) and electro- and impedance cardiography were recorded to obtain neural and cardiac stress reactivity, and saliva and blood samples were collected to determine cortisol, insulin and blood glucose.

Preliminary results showed that the MIST triggered a robust cortisol stress response and glucose intake increased blood glucose and insulin. Blood glucose –but not insulin– was positively correlated with post-stress cortisol levels. Further results of the preregistered analyses (https://osf.io/z6bpy/) employing growth curve models and regression analyses to assess the effects of the drinks on stress trajectories will be presented at the conference. The findings may advance our understanding of how short-term metabolic variations shape stress reactivity across neural, cardiovascular, and endocrine systems and thereby act as modulators of stress-related health outcomes.

Overcoming environmental challenges is essential for long-term physical and mental health. Adaptive responses to acute stress are critical in this regard, as the hypothalamic-pituitary-adrenal (HPA) axis mobilizes energy stores to meet stressor demands. A process mediated by cortisol-driven increases in glucose levels. However, most evidence comes from laboratory studies, and how glucose fluctuations shape stress experiences in daily life remains poorly understood.

To translate previous lab-based insights into a naturalistic setting, we analyzed 4,307 stress ratings (N=91, 47 women, M_BMI: 24.74 ± 4.09 kg/m²) collected over four weeks of ecological momentary assessment combined with continuous glucose monitoring. We will show that higher momentary glucose levels buffer self-reported stress (b = −.038, p = .035), even after accounting for changes in mood. Further, we will unravel the dynamic temporal relationship between glucose and stress experience: earlier glucose increases predict changes in stress several hours later (0–2h before EMA: p = .013; incremental effect 10–12h before: p < .001), highlighting the potential of physiological biosensor data for understanding and improving adaptive stress regulation.

Together, these findings underscore the strong link between mind and metabolism and its crucial role in daily stress regulation. The metabolic state is pivotal in the modulation of the subjective experience of stress in healthy adults. Ultimately, metabolic functioning may represent a promising target for interventions aimed at improving stress regulation and at bridging the mechanistic connection between mental and metabolic health.

Long COVID is a multisystem condition following SARS-CoV-2 infection, conceptualized as a maladaptive response to an initial physiological stressor. The resulting pathology is increasingly linked to dysfunction in autonomic processes that regulate brain–body interactions. Converging neuroinflammatory, autoimmune, and autonomic mechanisms suggest disrupted interoceptive allostasis, potentially impairing recovery from physical and cognitive stressors. Such impaired recovery may underlie key symptoms, including persistent fatigue, reduced stress tolerance, and cognitive dysfunction. Despite its multifaceted clinical presentation, stress regulation and recovery dynamics in Long COVID remain underexplored.

To target this mechanism, we investigate transcutaneous vagus nerve stimulation (tVNS) as a non-invasive intervention aimed at restoring autonomic balance and enhancing recovery following exertion. In a single-blind, randomized crossover trial (N = 120), participants complete two 6-week stimulation periods (active and low-intensity control), self-administered for up to 4 hours daily in a home-based setting. To capture real-world stress and recovery dynamics, we combine continuous wearable monitoring of physiological signals with ecological momentary assessments of mood, fatigue, and stress. This multimodal approach enables the characterization of individual physiological responses and provides insight into how autonomic regulation shapes recovery in everyday life.

Baseline data indicate distinct heart rate and variability patterns associated with symptom burden, while lower morning cortisol levels are linked to greater autonomic and depressive symptoms. Preliminary findings further suggest that increases in cortisol following high-intensity tVNS (relative to baseline) are associated with improvements in both somatic and mental health outcomes. These findings position tVNS as a promising tool to support adaptive stress recovery in Long COVID.