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The positive feedback model of medically-unexplained symptoms posits that chronic stress affects the activity of the physiological stress axes, which in turn generates medically-unexplained symptoms. As a first step to empirically test its model assumptions, we investigated potential associations between chronic stress, physiological stress axis activity and medically-unexplained in a cross-sectional study. One hundred-ninety-nine healthy individuals provided self-reports on chronic stress and medically-unexplained symptoms, resting heart rate/variability (HR/HRV; e.g., root mean square of successive differences/RMSSD, low frequency/LF power), cortisol awakening response (CAR) and diurnal cortisol. Significant positive contributors to medically-unexplained symptoms were the chronic stress scales 'lack of social appreciation' and 'chronic worries', as well as CAR and LF HRV; diurnal cortisol was a negative contributor. Mediation analyses showed that the impact of neural indicators associated with physiological stress axis activity (HR/HRV) related to medically-unexplained symptoms, which was mediated by chronic stress, whereas the mediation effect as suggested by the positive feedback model was not significant. These cross-sectional findings do not support the positive feedback model. Longitudinal studies are required to conclude about potential mechanistic and causal relationships in the model. Nevertheless, our mediation analyses give first indication that the constitution of physiological stress axes may play a major role in how stressors are perceived and which kind of health-consequences (e.g., medically-unexplained symptoms) this may have., Competing Interests: Declaration of Competing Interest None of the authors has to declare a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

When studying the factors which influence stress reactivity in within-subject designs, test-retest reproducibility data is needed to estimate power and sample size. We report such data regarding a new experimental stress protocol, based on simultaneous application of the socially evaluated, bilateral feet Cold Pressor Test (CPT) and the Paced Auditory Serial Addition Task (PASAT). Cardiovascular, neuroendocrine, and subjective (affective) stress responses of 32 healthy males were measured twice, at an interval of one week. The novel protocol induced substantial stress reactivity in all parameters at both test and retest. Cardiovascular reactivity remained unchanged, but cortisol and subjective responses were lower at second stress exposure, with high test-retest stability of neuroendocrine (r>.7) and cardiovascular measures (r = .5 to r = .9). PASAT performance improved. Response attenuation suggests habituation-like and/or learning effects. Data provided by our study demonstrate feasibility and power of this stress protocol for investigating changes in stress reactivity in repeated, within-subject designs., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Frontal EEG asymmetry has been proposed as an index of emotional regulation, reflecting both state and trait components, and there is evidence that these factors influence the cortisol response to stress. Here, we asked whether cold pressor stress modulates frontal asymmetry and whether this is predictive of the neuroendocrine stress response. Twenty-four male participants underwent an automatized bilateral feet cold pressor test (bfCPT) and a warm water control procedure in counterbalanced order on two separate days, one week apart. EEG, heart rate and blood pressure were assessed at baseline as well as during and after the bfCPT. Salivary cortisol and subjective ratings of stress and arousal were assessed before and after the bfCPT. The bfCPT led to a significant increase in cortisol, cardiovascular parameters and in subjective ratings of stress and arousal that was absent in the control condition. Furthermore, analysis of relative frontal alpha-band asymmetry revealed a stronger relative right frontal activation during the bfCPT compared to the control condition at electrode pairs F7/8 but not F3/4. However, frontal asymmetry scores during the bfCPT were not predictive for neither physiological responses nor subjective ratings. Moreover, an association between physiological responses and frontal asymmetry assessed during rest at baseline could be observed at electrode pairs F3/F4, with stronger responses being associated with stronger relative right frontal activation. Our results show that cold pressor stress leads to an alteration of emotional processes as reflected in frontal EEG asymmetry at F7/F8. Moreover, physiological responses to the CPT seem to be differentially moderated by trait and state components present in frontal asymmetry., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chronic stress attenuates reproductive behavior in many species, but evidence regarding the impact of acute stress on human sexual arousability is insufficient. Stressor-specific effects might result from divergent roles of both stress response systems. Social self-threat, linked to affiliation-oriented coping, might also influence sexual responsivity. To investigate stress-induced modulation of the processing of sexual cues and its relationship with cortisol, 58 participants underwent either a predominantly sympathetic stressor (3 min sustained handgrip) or similar control procedure. In both conditions, half of the sample was monitored by an opposite-sex person (social evaluation). Pupillary responses to erotic nudes were recorded and dissociated into fast and slow PCA components. Physically stressed participants showed enhanced (slow) dilation to explicit pictures. Cortisol levels after stress negatively predicted rapid responses to opposite-sex and (marginally) explicit stimuli. Our results suggest that acute sympathetic stress exposure facilitates cognitive sexual processing, whereas subsequent HPA-axis activation may induce counteracting effects., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In response to stress, physiological and mental resources are allocated towards those systems that are needed for rapid responding in terms of fight or flight. On the other hand, long term regenerative processes such as growth, digestion and reproduction are attenuated. Levels of the sex steroid testosterone are reduced in participants that suffer from chronic stress. However, beyond its role for reproductive functions, testosterone plays an important role in the regulation of social status and dominance, testosterone levels increase during competition or when the social status is challenged. The Trier Social Stress Test (TSST), a laboratory stressor with a substantial social-evaluative component, can provoke an increase in salivary testosterone levels. Still, so far the reported findings regarding acute stress effects on testosterone are equivocal, possibly due to moderating effects. In this study we experimentally manipulated social dominance in 56 healthy participants (28m) by two independent manipulations (body posture and cognitive role taking) and subjected them to the TSST. We analyzed salivary testosterone and cortisol levels as dependent measures for the endocrine stress response. The role taking manipulation interacted with the testosterone response: we found the strongest increase when participants had to put themselves in a dominant (vs. submissive) role. Our results suggest that transient changes in testosterone levels during stress reflect a response to status threat that is affected by social dominance., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Changes within the cardiovascular system have been shown to alter sensorimotor and memory performance, pain perception as well as cortical arousal. This influence is assumed to be mediated by afferent feedback of baroreceptors that when stimulated exert inhibitory effects on cortical structures. Mainly responsible for short-term regulation of blood pressure, afferents of the baroreceptors are widely connected to subcortical and cortical structures like the insular cortex. A putative impact on cognitive control processes remains an open question, however. Using a sequential distractor priming task, the present study investigated whether inhibitory influences of baroreceptor activation apply to selective information processing in the presence of irrelevant information. In particular, we assessed distractor-response binding and Negative Priming as indices of automatic and controlled distractor processing, respectively. Baroreceptor activation was experimentally manipulated by the systematic variation of body position. The results showed that only Negative Priming but not distractor-response binding was modulated by body position suggesting that controlled but not automatic processing of distractors is affected by baroreceptor activity., (Copyright © 2015. Published by Elsevier B.V.)

Motivational states may be induced by affective foreground stimulation or via proprioceptive feedback by certain postures or body movements. In the present study, we addressed the question of an interaction between basic motor actions and the valence of visual stimuli in an affective modulation of startle paradigm: is the potentiation for aversive and the attenuation for pleasant stimuli more pronounced when the muscles for a congruent approach or avoidance action are activated? Thirty-four volunteers (20 female) watched emotional pictures on a computer screen while simultaneously contracting the flexor vs. extensor muscles of the upper arm. After 3-4s, an acoustic startle stimulus (105dB, binaural, instantaneous rise time) was presented via headphones. Arm movement interacted with picture valence: flexion, compared to extension, increased affective startle modulation (F=4.32, p<0.05). This result suggests integration and not simple summation of postural and body movement effects on startle reflexivity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Research on the interaction of the cardiovascular and the central nervous system has demonstrated inhibitory effects associated with baroreceptor stimulation. One way of examining baroreceptor influence on behavior and central nervous processes is by making use of naturally occurring variations in baroreceptor stimulation in the course of the cardiac cycle. In terms of perceptual and sensorimotor processes, until today, research has focused primarily on cardiac cycle time effects on the perception of and reaction to simple stimuli. The present study is the first to investigate modulatory effects of variations in baroreceptor activity in the context of a more complex stimulus configuration using a visual masking task in which a target has to be selected against an interfering mask. The results suggest that baroreceptor stimulation enhances inhibitory processes needed to solve perceptual interference., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Interoception depends on visceral afferent neurotraffic and central control processes. Physiological arousal and organ activation provide the biochemical and mechanical basis for visceral afferent neurotraffic. Perception of visceral symptoms occurs when attention is directed toward body sensations. Clinical studies suggest that stress contributes to the generation of visceral symptoms. However, during stress exposure attention is normally shifted away from bodily signals. Therefore, the net effects of stress on interoception remain unclear. We, therefore, investigated the impact of the cold pressor test or a control intervention (each n=21) on three established laboratory paradigms to assess cardioceptive accuracy (CA): for the Schandry-paradigm, participants were asked to count heartbeats, while during the Whitehead-tasks subjects were asked to rate whether a cardiac sensation appeared simultaneously with an auditory or visual stimulus. CA was increased by stress when attention was focused on visceral sensations (Schandry), while it decreased when attention was additionally directed toward external stimuli (visual Whitehead). Explanations for these results are offered in terms of internal versus external deployment of attention, as well as specific effects of the cold pressor on the cardiovascular system., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The binding of stimulus and response features into SR episodes or "event files" is a basic process for the efficient control of behavior. However, relevant information is usually accompanied by information that is irrelevant for the selection of action and recent studies showed that this irrelevant information is also bound into event files. In this study, we investigated the possible modulation of distractor-response binding due to stress. To this end, participants were treated with a variant of the cold pressure stress test and worked through a binding experiment before and directly after the stress treatment. Physiological and subjective stress measures were surveyed and did predict the change in binding effects: binding in stressed participants ceased as compared to a non-stressed control group. Increases in cortisol and blood pressure are discussed as main reasons for decreased SR retrieval., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Cardiac modulation of startle eye blink has been introduced as a methodology to reflect baro-afferent signal transmission. Recent studies showed that affective startle modulation is specific to left-ear presentation that may be due to hemispheric specificity in processing emotional-relevant stimuli, similar to the processing of visceral- and baro-afferent stimuli. To explore whether cardiac modulation of startle eye blink is lateralized as well, 37 healthy volunteers received 160 unilateral acoustic startle probes of 105 dB(A) intensity presented to both ears, one at a time. They were elicited 0, 100, 230, and 530 ms after the R-wave of the cardiac cycle. Startle response magnitude was significantly diminished at a latency of 230 ms, which may be due to the baro-afferent neural feedback at this temporal location, but only for left-ear presentation. This lateralization effect in the cardiac modulation of startle eye blink may reflect the previously described advantages of right-hemispheric brain structures in relaying viscero- and baro-afferent signal transmission.