Hyperoxia-induced alterations in cardiovascular function and autonomic control during return to normoxic breathing

Hyperoxia causes hemodynamic alterations. We hypothesized that cardiovascular and autonomic control changes last beyond the end of hyperoxic period into normoxia. Ten healthy volunteers were randomized to breathe either medical air or 100% oxygen for 45 min in a double-blind study design. Measurements were performed before (baseline) and during gas exposure, and then 10, 30, 60, and 90 min after gas exposure. Hemodynamic changes were studied by Doppler echocardiography. Changes in cardiac and vasomotor autonomic control were evaluated through changes in spectral power of heart rate variability and blood pressure variability. Cardiac baroreflex sensitivity was assessed by the sequence method. Hyperoxia significantly decreased heart rate and increased the high frequency power of heart rate variability, suggesting a chemoreflex increase in vagal activity since the slope of cardiac baroreflex was significantly decreased during hyperoxia. Hyperoxia increased significantly the systemic vascular resistances and decreased the low frequency power of blood pressure variability, suggesting that hyperoxic vasoconstriction was not supported by an increase in vascular sympathetic stimulation. These changes lasted for 10 min after hyperoxia (p < 0.05). After the end of hyperoxic exposure, the shift of the power spectral distribution of heart rate variability toward a pattern of increased cardiac sympathetic activity lasted for 30 min (p < 0.05), reflecting a resuming of baseline autonomic balance. Cardiac output and stroke volume were significantly decreased during hyperoxia and returned to baseline values (10 min) later than heart rate. In conclusion, hyperoxia effects continue during return to normoxic breathing, but cardiac and vascular parameters followed different time courses of recovery.     

The heart rate increase at the onset of high-work intensity exercise is accelerated by central blood volume loading

Using a water immersion (WI) method, the combined effect of central blood volume (CBV) loading and work intensity on the time course of heart rate (HR) at the onset of upright dynamic exercise was investigated. Seven males cranked a cycle ergometer for 12 min using their un-immersed arms at low-, moderate- and high-work intensities, followed by a 12-min rest. For WI, the pre-exercise resting cardiac output increased by 36%, while HR decreased by 22% [from 76.8 (10.4) to 59.6 (9.8) beats/min]. WI also increased the high-frequency (HF, 0.15–0.40 Hz) component of the HR variability, suggesting an increased vagal activity. During the initial 2 min of the exercise period at low-work intensity, HR increased by 34.9 and 25.8% in the WI and control conditions, respectively. These were 117 and 73% at high-work intensity, indicating more accelerated HR with WI than the control. The plasma norepinephrine concentration increased less during high-work intensity exercise during WI, as compared to exercise during control conditions. In conclusion, the HR increase at the onset of high-work intensity exercise is accelerated by CBV loading but not at low intensity, possibly reflecting vago-sympathetic interaction and reduced baroreflex sensitivity.     

Effects of exercise intensity and duration on nocturnal heart rate variability and sleep quality

Acute physical exercise may affect cardiac autonomic modulation hours or even days during the recovery phase. Although sleep is an essential recovery period, the information on nocturnal autonomic modulation indicated by heart rate variability (HRV) after different exercises is mostly lacking. Therefore, this study investigated the effects of exercise intensity and duration on nocturnal HR, HRV, HR, and HRV-based relaxation, as well as on actigraphic and subjective sleep quality. Fourteen healthy male subjects (age 36 ± 4 years, maximal oxygen uptake 49 ± 4 ml/kg/min) performed five different running exercises on separate occasions starting at 6 p.m. with HR guidance at home. The effect of intensity was studied with 30 min of exercises at intensities corresponding to HR level at 45% (easy), 60% (moderate) and 75% (vigorous) of their maximal oxygen uptake. The effect of duration was studied with 30, 60, and 90 min of moderate exercises. Increased exercise intensity elevated nocturnal HR compared to control day (p < 0.001), but it did not affect nocturnal HRV. Nocturnal HR was greater after the day with 90- than 30- or 60-min exercises (p < 0.01) or control day (p < 0.001). Nocturnal HRV was lower after the 90-min exercise day compared to control day (p < 0.01). Neither exercise intensity nor duration had any impact on actigraphic or subjective sleep quality. The results suggest that increased exercise intensity and/or duration cause delayed recovery of nocturnal cardiac autonomic modulation, although long exercise duration was needed to induce changes in nocturnal HRV. Increased exercise intensity or duration does not seem to disrupt sleep quality.     

Effects of stress on heart rate complexity—A comparison between short-term and chronic stress

This study examined chronic and short-term stress effects on heart rate variability (HRV), comparing time, frequency and phase domain (complexity) measures in 50 healthy adults. The hassles frequency subscale of the combined hassles and uplifts scale (CHUS) was used to measure chronic stress. Short-term stressor reactivity was assessed with a speech task. HRV measures were determined via surface electrocardiogram (ECG). Because respiration rate decreased during the speech task (p < .001), this study assessed the influence of respiration rate changes on the effects of interest. A series of repeated-measures analyses of covariance (ANCOVA) with Bonferroni adjustment revealed that short-term stress decreased HR D2 (calculated via the pointwise correlation dimension PD2) (p < .001), but increased HR mean (p < .001), standard deviation of R–R (SD_RR) intervals (p < .001), low (LF) (p < .001) and high frequency band power (HF) (p = .009). Respiratory sinus arrhythmia (RSA) and LF/HF ratio did not change under short-term stress. Partial correlation adjusting for respiration rate showed that HR D2 was associated with chronic stress (r = −.35, p = .019). Differential effects of chronic and short-term stress were observed on several HRV measures. HR D2 decreased under both stress conditions reflecting lowered functionality of the cardiac pacemaker. The results confirm the importance of complexity metrics in modern stress research on HRV.     

Cardiac and autonomic function in patients with Crohn’s disease during remission

Purpose

The aim of the study was to assess cardiac and autonomic function in patients with Crohn’s disease and explore their relation to disease duration using cardiovascular reflex tests.

Usefulness of cardiac parasympathetic index in CPAP‐treated patients with obstructive sleep apnea: A preliminary study

Cardiac autonomic indexes, including cardiac parasympathetic index and cardiac sympathetic index, have been reported to accurately identify patients with sleep disorders such as obstructive sleep apnea. Our study aimed to assess cardiac autonomic indexes in patients with obstructive sleep apnea before and during a single full‐night continuous positive airway pressure therapy using a combined approach. Our simultaneous heart rate variability‐polysomnographic study included 16 never‐treated obstructive sleep apnea patients. Two patients dropped out. Patients underwent combined recordings in two consecutive days, at baseline and during a single full‐night of acute continuous positive airway pressure treatment. We calculated cardiac parasympathetic index and cardiac sympathetic index as night/day ratio for high‐frequency and low‐frequency heart rate variability spectral components, respectively. Continuous positive airway pressure treatment significantly reduced cardiac autonomic indexes values in comparison with baseline values (cardiac parasympathetic index: p < .0001; cardiac sympathetic index: p = .001). After acute continuous positive airway pressure treatment, the percentage of decrease of cardiac parasympathetic index was greater than that of cardiac sympathetic index (51.02 ± 15.72 versus 34.64 ± 26.93). A positive statistical correlation was also found between decrease of cardiac parasympathetic index and decrease of apnea–hypopnea index after continuous positive airway pressure (p < .001). This study improves the knowledge on cardiac autonomic modulation during acute continuous positive airway pressure therapy in obstructive sleep apnea. Our results demonstrate that both autonomic indexes decreased significantly after a single‐night of acute continuous positive airway pressure therapy. Cardiac parasympathetic index more than cardiac sympathetic index was related to decrease of apnea–hypopnea index after continuous positive airway pressure therapy, thus representing a potential help in everyday clinical practice.     

Exercise-induced plasma volume expansion and post-exercise parasympathetic reactivation

The purpose of this study was to investigate the effect of exercise-induced plasma volume expansion on post-exercise parasympathetic reactivation. Before (D₀) and 2 days after (D₊₂) a supramaximal exercise session, 11 men (21.4 ± 2.6 years and BMI = 23.0 ± 1.4) performed 6-min of submaximal running where heart rate (HR) recovery (HRR) and HR variability (HRV) indices were calculated during the first 10 min of recovery. Relative plasma volume changes (∆PV) were calculated using changes in hematocrit and hemoglobin measured over consecutive mornings from D₀ to D₊₂. Parasympathetic reactivation was evaluated through HRR and vagal-related indexes calculated during a stationary period of recovery. Compared with D₀, ∆PV (+4.8%, P < 0.01) and all vagal-related HRV indices were significantly higher at D₊₂ (all P < 0.05). HRR was not different between trials. Changes in HRV indices, but not HRR, were related to ∆PV (all P < 0.01). HRR and HRV indices characterize distinct independent aspects of cardiac parasympathetic function, with HRV indices being more sensitive to changes in plasma volume than HRR.     

Association of breathing movements to the variability of heart rate and blood pressure in foetal lambs

Heart rate (HR) variability and arterial blood pressure (BP) variability were analysed as functions of foetal breathing movements (FBMs) by means of power spectral analysis in seven foetal lambs during the third trimester of gestation. No evidence of FBM-related changes, either in mean HR, mean systolic or diastolic arterial pressures, were found. Mean arterial pulse pressure, HR variability, and BP variability increased during FBMs. The increase in BP variability occurred at frequencies higher than 0.35 Hz, i.e. those of FBMs. The increase in HR variability occurred at 0.07-1.0 Hz, i.e. at every frequency band except the lowest one. Thus, the increase in HR variability was not frequency-specifically related to FBMs. During FBMs the periodic variability of HR at frequencies > 0.35 Hz was only 10% of total HR variability. We suggest that the FBM-related changes of BP variability may be mediated by direct peripheral, hydraulic mechanisms. HR changes involve autonomic control systems: the vagal component of baroreflex seems to be relatively insensitive, whereas the very slow vasomotor component of HR variability is dominant.     

The effect of 60-h sleep deprivation on cardiovascular regulation and body temperature

This study examined cardiovascular regulation and body temperature (BT) during 60 h of sleep deprivation in 20 young healthy cadets. Heart rate variability was measured during an active orthostatic test (AOT). Measurements were performed each day in the morning and evening after 2, 14, 26, 38, 50 and 60 h of sleep deprivation. In AOT, in the sitting and standing positions, heart rate decreased (P < 0.001), while high frequency and low frequency power increased (P < 0.05–0.001) during sleep deprivation. Body temperature also decreased (P < 0.001), but no changes were detected in blood pressure. In conclusion, the accumulation of 60 h of sleep loss resulted in increased vagal outflow, as evidenced by decreased heart rate. In addition, BT decreased during sleep deprivation. Thus, sleep deprivation causes alterations in autonomic regulation of the heart, and in thermoregulation.     

Effects of long-term exercise training on cardiac autonomic nervous activities and baroreflex sensitivity

Reductions in tonic vagal controls of the heart and depressed baroreflex sensitivity (BRS) have been associated with a postural fall in blood pressure (BP) and the incidence of cardiac events among older people. We examined the hypothesis that BP regulation during orthostatic challenge as well as heart rate variability (HRV) at rest can be better maintained in long-term exercise-trained, healthy, older men (aged 60–70 years). Subjects were classified into two groups; long-term exercise-trained (LTET, n=14) and sedentary (SED, n=10) according to their history of physical activity. Prior to the dynamic BRS assessment, supine resting autonomic cardiac modulation was assessed by means of time domain HRV [standard deviation of ECG R–R interval (RRISD) and the coefficient of variation (CV)]. The BRS was assessed during 60° head-up tilting by simultaneously measuring beat-by-beat systolic blood pressure (SBP) and ECG R–R interval changes. The BRS gain was determined by the regression slope coefficient based on the extent of the SBP fall and the corresponding ECG R–R shortening during the orthostatic challenge. The results indicated that the LTET group manifested greater ECG R–R interval fluctuations with significantly higher resting RRISD and CV, compared with the SED group [59.5 (10.4) versus 27.7 (7.8) ms, p<0.05; 5.5 (0.8) versus 2.8 (0.7)%, p<0.05], respectively. Using dynamic BRS testing during the acute orthostatic challenge, the LTET group showed a significantly higher BRS gain than the SED [6.4 (0.8) versus 3.8 (0.6) ms·mmHg⁻¹, p<0.017] group. These results indicate that CV and BRS are well maintained in healthy, LTET older individuals when compared with their sedentary peers. Our data suggest that this augmented autonomic cardiac modulation reflects better parasympathetic responsiveness in LTET individuals. Data provide further support for long-term exercise training as another possible cardioprotective factor that might decrease susceptibility to ventricular fibrillation as well as assist arterial BP at the onset of an orthostatic challenge in older men. Electronic Publication     

Heart rate dynamics after controlled training followed by a home-based exercise program

Daily aerobic training results in autonomic control of the heart toward vagal dominance. The constancy of vagal dominance after controlled training followed by a home-based training program in accordance with contemporary guidelines is not known. We set out here to study whether the vagal dominance induced by 8 weeks of controlled aerobic training is preserved after a 10-month home-based training program. For the controlled study, healthy men were randomized as training (n=18) and control subjects (n=6). The training was started by a supervised 8-week period with six training sessions a week [45 (15) min each] at an intensity of 70–80% of maximum heart rate, followed by a home-based training program for 10 months in accordance with the American College of Sports Medicine recommendations. Cardiovascular autonomic function was assessed by analyzing HR variability over a 24-h period and separately during the night hours (midnight–6 a.m.). Maximal running performance improved during the controlled training 16 (7)% (range 4–31%, P<0.001) and remained 8 (8)% (range –3 to 23%, P<0.001) above the baseline level after the home-based training program. At night, the vagally mediated high-frequency (HF) power of R-R intervals increased during the controlled training from 6.7 (1.3) to 7.3 (1.1) ln ms² (P<0.001) and remained higher than the baseline after the home-based training [7.0 (1.3) ln ms², P<0.05]. The changes in running performance correlated with the changes in HF power at night (r=0.41, P<0.05) and over 24 h (r=0.44, P<0.05) after the home-based training program. Similarly, the changes in body mass index correlated with the changes in HF power over 24 h (r=–0.44, P<0.05) after the home-based training program. The high vagal outflow to the heart after the home-based training is associated with good physical performance and body mass control.     

Autonomic activity and baroreflex sensitivity in patients submitted to carotid stenting

Arterial baroreflex and cardiac autonomic control play important roles in hemodynamic instability after carotid artery stenting (CAS). Spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and blood pressure variability (BPV) are established tools for the assessment of arterial baroreflex and cardiac autonomic activity. Aim of the study was to evaluate cardiac autonomic activity (by means of HRV, BPV and BRS) after CAS and to explore the impact of internal carotid artery stenosis on BRS changes after CAS. 37 patients (68±10.45 years) with internal carotid stenosis underwent CAS. HRV, BPV and BRS were measured in all subjects before and at 1 and 72h after CAS. ANOVA was performed to compare BRS, HRV and BPV parameters before and after CAS. Spearman analysis was performed to determine a possible correlation between carotid stenosis degree (or carotid plaque diameter) and BRS changes (ΔBRS). LF/HF (index of sympatho-vagal balance) decreased during postoperative period, in comparison with baseline (2.32±1.70 vs 1.65±1.40, p<0.05). There was a significant negative correlation between carotid stenosis degree and ΔBRS (r=-0.35, p=0.03) and between carotid plaques thickness and ΔBRS (r=-0.36, p=0.02). CAS procedure may cause an alteration of carotid wall mechanical properties, increasing baroreflex sensitivity. BRS does not increase in all the patients, because arterial wall damage and nerve destruction determined by atherosclerotic plaque may reduce ΔBRS.     

Physiological stress responses in defensive individuals: Age and sex matter

The association between defensiveness and physiological responses to stress were evaluated in 81 healthy working men and 118 women, aged 20 to 64 years (M=41; SD=11.45). Participants underwent laboratory testing during which they were exposed to interpersonal stressors. Heart rate (HR), heart rate variability (HRV), blood pressure (BP), and salivary cortisol were measured. Defensiveness was evaluated using the Marlowe‐Crowne Social Desirability Scale. In women, higher defensiveness was associated with greater BP and HR reactivity to stress (p<.05). In older men, lower defensiveness was associated with increased systolic BP reactivity to stress (p<.02), delayed HRV recovery (p<.02), and greater salivary cortisol levels (p<.02). In conclusion, greater defensiveness was associated with increased reactivity to stress in women whereas in older men, lower defensiveness was associated with elevated cardiovascular, autonomic, and endocrine responses to stress.     

Post-exercise recovery of autonomic cardiovascular control: a study by spectrum and cross-spectrum analysis in humans

The recovery of the baseline autonomic control of cardiovascular activity after exercise has not been extensively studied. In 12 healthy subjects, we assessed the time-course of recovery by autoregressive spectrum and cross-spectrum analysis of heart period and systolic blood pressure during the 3 h after the end of 20 min of steady-state exercise at 50% (light workload, LW) and 80% (moderate workload, MW) of the individual's anaerobic threshold. The electrocardiogram and non-invasive blood pressure were simultaneously recorded during 10 min periods in the sitting position, at rest before exercise, and at 15, 60 and 180 min of recovery after exercise. At 15 min we observed a persistent tachycardia and relative hypotension; after MW, at 60 min heart rate was still slightly higher. Spectrum and cross-spectrum analysis showed, at 15 min, an increase in the low frequency component of systolic blood pressure, a reduction in the high frequency component of heart rate (larger in MW), and a decrease in baroreceptor sensitivity. After 60 and 180 min none of these parameters was significantly different from those at rest, although, in MW, some subjects still displayed signs of sympathetic activation after 1 h. We concluded that, after 15 min of recovery, the cardiovascular reflexes were blunted, that sympathetic nerve activity was still enhanced, and that the tone in the vagus had not fully recovered. Only the persistent vagal restraint seemed to be exercise intensity-dependent. For complete restoration of autonomic control after LW 1 h of rest was sufficient, and just enough after MW. Accepted: 2 November 2000     

Reproducibility of heart rate variability and baroreflex sensitivity measurements in children

Despite their extensive use, the reproducibility of cardiac autonomic measurements in children is not well-known. We investigated the reproducibility of short-term continuous measurements of heart rate (HR), heart rate variability (HRV, time and frequency domain), and spontaneous baroreflex sensitivity (BRS, frequency domain) in the supine and standing position in 57 children (11.2 ± 0.7 years, 52.6% boys). Reproducibility between two sessions within a two-week interval was evaluated by intraclass correlation coefficients (ICCs), standard error of measurement, coefficients of variation (CVs), limits of agreement, and Bland-Altman plots. HR and HRV were moderately-to-highly (ICC = .63-.79; CV = 5.7%-9.7%) and BRS moderately (ICC = .49-.63; CV = 11.4%-14.0%) reproducible. While the BRS measurements were slightly less reproducible than the HR and HRV measurements, all can be reliably applied in research, thus implicating sufficient capacity to detect real differences between children. Still, clinical studies focusing on individual changes in cardiac autonomic functioning need to address the considerable random variations that may occur between test-retest measurements.     

Heart rate variability during dynamic exercise in elderly males and females

It has been proposed that cardiac control is altered in the elderly. Power spectral analysis of heart rate variability (HRV) was performed on 12 male and 11 female elderly subjects (mean age 74 years) while at rest in supine and sitting positions, and at steady states during 5 min of exercise (35–95% peak oxygen consumption, V˙O_2peak). There were no differences in power, measured as a percentage of the total of the high frequency peak (HF, centred at about 0.25 Hz; 13% in males vs 12% in females), low frequency peak (LF, centred at 0.09 Hz; 25% in males and 22% in females), and very low frequency component (VLF, at 0.03 Hz; 66% in males and 69% in females) between body positions at rest. There was no difference in spectral power between male and female subjects. Total power decreased as a function of oxygen consumption during exercise, LF% did not change up to about 14 ml · kg⁻¹ · min⁻¹ (40% and 80% V˙O_2peak in males and females, respectively), then decreased towards minimal values in both genders. HF% power and central frequency increased linearly with metabolic demand, reaching higher values in male subjects than in female subjects at V˙O_2peak, while VLF% remained unchanged. Thus, the power spectra components of HRV did not reflect the changes in autonomic activity that occur at increasing exercise intensities, confirming previous findings in young subjects, and indicated similar responses in both genders. Accepted: 30 November 1999     

Influence of age on blood pressure recovery after maximal effort ergometer exercise in non-athletic adult males

This study investigated whether age influences blood pressure recovery after maximal exercise in adult males. Forty healthy, non-athletic adult males (20 young, aged 22 ± 3.46 years and 20 older, aged 48 ± 6.91 years) participated in the study. Subjects performed a maximal-effort ergometer exercise test. Peak oxygen uptake (VO_2max) was measured during the exercise protocol; heart rate (HR) and blood pressure (BP) were measured before exercise, during exercise (at 2-min intervals), and at the first minute of post-exercise recovery and subsequently at 2-min intervals until the recovery of BP. Results indicated that young adults had lower systolic blood pressure (SBP) recovery ratio (P < 0.05), lower SBP recovery time (P < 0.001), higher SBP% decline in 1, and 3 min (P < 0.001), and higher DBP% decline in 1, and 3 min (P < 0.05, <0.001) than the older adults, thus indicating faster BP recovery in young than older adults. A bivariate correlation test, revealed significant associations (P < 0.001, <0.01) between age and BP recovery parameters: percentage SBP decline in 1 and 3 min (27 and 39%), percentage DBP decline in 1 and 3 min (14 and 26%), third minute SBP ratio (22%), and SBP recovery time (72%). After controlling for factors affecting BP recovery such as resting SBP, percentage HR decline, VO_2max and delta SBP, the observed correlations reduced in SBP recovery time (29%; P < 0.002) but disappeared (P > 0.01) in the other BP recovery parameters. These data indicate the need to take into account, factors affecting BP recovery when interpreting the effect of age on BP responses after exercise in future investigations.     

Dominance in cardiac parasympathetic activity during real recreational SCUBA diving

It was already established that exposure to hyperbaric conditions induces vagal-depended bradycardia but field study on autonomic nervous system (ANS) activity during self-contained underwater breathing apparatus (SCUBA) diving is lacking. The aim of the present study was to evaluate ANS modifications during real recreational SCUBA diving using heart rate variability analysis (timedomain, frequency-domain and Poincaré plot) in 10 experienced and volunteers recreational divers. Mean RR, root mean square of successive differences of interval (rMSSD), high frequency of spectral analysis and standard deviation 1 of Poincaré Plot increased (P < 0.05) during dive. Low frequency/high frequency ratio decreased during dive (P < 0.05) but increased after (P < 0.05). Recreational SCUBA diving induced a rise in vagal activity and a decrease in cardiac sympathetic activity. Conversely, sympathetic activity increases (P < 0.05) during the recovery.     

Consistency of heart rate and sympathovagal reactivity across different autonomic contexts

Theories that psychophysiological reactivity constitutes a risk factor for coronary artery disease assume that reactivity is a consistent individual characteristic. We tested this assumption by measuring reactivity to three psychologically challenging tasks performed by 22 healthy subjects across different autonomic contexts produced by positional change. Dependent variables included heart rate (HR), low-frequency (LF; 0.04–0.15 Hz) and high-frequency (HF; 0.15–0.50Hz) heart period variability, and the LF/HF ratio. HR (r= .44, p < .05) and LF/HF ratio (r= .48, p= .03) reactivity were modestly correlated across the different autonomic contexts, but HF and LF power reactivity were not. These findings suggest that HR reactivity to psychological challenge is a modestly consistent characteristic of individuals, despite differences in autonomic context. Although the same is true of cardiac sympathovagal balance, reactivity of HF and LF power were less consistent.     

Associations between digit ratio (2D4D), mood,and autonomic stress response in healthy men

The ratio between the length of the second (index) and the fourth (ring) finger (2D4D) is a putative biomarker of prenatal testosterone (T) exposure, with higher exposure leading to a smaller ratio. 2D4D has further been linked to mental and somatic disorders. Healthy male Swiss recruits (N = 245; M_age = 20.30 years) underwent a psychosocial stress test. Mood and salivary alpha‐amylase (sAA) were assessed before and after the stress test, while heart rate (HR) and heart rate variability (HRV) were measured continuously. Additionally, 2D4D (right: R2D4D; left: L2D4D) was determined and divided into quartile groups. Correlation analysis showed no associations between R/L2D4D and outcome measures. Comparing calculated quartiles for R2D4D, subjects in the lowest R2D4D quartile expressed trendwise (p < 0.10) lower positive and higher negative affect, significantly elevated sAA activity (p < 0.05), but no HR and HRV differences at baseline as compared to subjects in the upper three quartiles. With regard to acute stress, subjects in the lowest as compared to subjects in the upper three R2D4D quartiles showed a higher increase of negative affect and a stronger cardiac response (p < 0.05), but no alterations in positive affect and sAA activity. Young healthy men in the lowest R2D4D quartile revealed a more negative affect and increased physiological activity at baseline and in response to acute stress. An exposure to high levels of prenatal T might constitute a risk factor potentially increasing vulnerability to stress‐related disorders in men.