Serotonin Modulates the Correlations between Obsessive-compulsive Trait and Heart Rate Variability in Normal Healthy Subjects: A SPECT Study with [123I]ADAM and Heart Rate Variability Measurement.

Top-down regulation in the human brain and anatomical connections between the prefrontal cortex (PFC) and specific catecholamine-related regions have been well-studied. However, the way in which the PFC modulates downstream neuro-networks in terms of serotonin and the autonomic nervous system (ANS) by variation in the level of brain-derived neurotrophic factor (BDNF) is still unclear. We recruited sixty-seven healthy subjects. Serotonin transporter (SERT) availability was examined by SPECT with [123I]ADAM analysis; heart rate variability (HRV) testing was performed, and the BDNF level was measured. The Wisconsin card-sorting test (WCST), which assesses PFC activation, was also conducted. The interactions of BDNF level and SERT availability were significant in relation to the HRV indexes of low frequency, high frequency, total power, and mean heart rate range. Moderate to significant positive correlations between SERT availability and the above-mentioned HRV indexes existed only in subjects with a low BDNF level. Furthermore, in the low BDNF level group, only those with high WCST perseveration errors or low category completions exhibited significant positive correlations between SERT availability and HRV indexes. A lower BDNF level and poorer PFC function might modulate the synergistic effects of serotonergic and ANS systems in order to maintain brain physiological and psychological homeostasis.

Passive translational acceleration (PTA) has been demonstrated to induce the stress response and regulation of autonomic balance in healthy individuals. Electrodermal activity (EDA) and heart rate variability (HRV) measurements are reliable indicators of the autonomic nervous system (ANS) and can be used to assess stress levels. The objective of this study was to investigate the potential of combining EDA and HRV measurements in assessing the physiological stress response induced by PTA. Fourteen healthy subjects were randomly assigned to two groups of equal size. The experimental group underwent five trials of elevator rides, while the control group received a sham treatment. EDA and HRV indices were obtained via ultra-short-term analysis and compared between the two groups to track changes in the ANS. In addition, the complexity of the EDA time series was compared between the 4 s before and the 2–6 s after the onset of PTA to assess changes in the subjects' stress levels in the experimental group. The results revealed a significant increase in the skin conductance response (SCR) frequency and a decrease in the root mean square of successive differences (RMSSD) and high frequency (HF) components of HRV. In terms of stress assessment, the results showed an increase in the complexity of the EDA time series 2–6 s after the onset of PTA. These results indicate an elevation in sympathetic tone when healthy subjects were exposed to a translational transport scenario. Furthermore, evidence was provided for the ability of EDA complexity to differentiate stress states in individual trials of translational acceleration.

Various non-electrocardiogram (ECG) based methods are considered reliable sources of heart rate variability (HRV) measurement. However, the ultra-short recording of a femoral arterial waveform has never been validated against the gold-standard ECG-based 300s HRV and was the aim of this study.A validity study was conducted using a sample from the first follow-up of the longitudinal ADVANCE study UK. The participants were adult servicemen (n = 100); similar in age, rank, and deployment period (Afghanistan 2003–2014). The femoral arterial waveforms (14s) from the pulse wave velocity (PWV) assessment, and ECG (300s) were recorded at rest in the supine position using the Vicorder™ and Bittium Faros™ devices, respectively, in the same session. HRV analysis was performed using Kubios Premium. Resting heart rate (HR) and root mean square of successive differences (RMSSD) were reported. The Bland-Altman %plots were constructed to explore the PWV-ECG agreement in HRV measurement. A further exploratory analysis was conducted across methods and durations.The participants’ mean age was 38.0 ± 5.3 years. Both PWV-derived HR (r = 0.85) and RMSSD (rs=0.84) showed strong correlations with their 300s-ECG counterparts (p < 0.001). Mean HR was significantly higher with ECG than PWV (mean bias: -12.71 ± 7.73%, 95%CI: -14.25%, -11.18%). In contrast, the difference in RMSSD between the two methods was non-significant [mean bias: -2.90 ± 37.82% (95%CI: -10.40%, 4.60%)] indicating good agreement. An exploratory analysis of 14s ECG-vs-300s ECG measurement revealed strong agreement in both RMSSD and HR.The 14s PWV-derived RMSSD strongly agrees with the gold-standard (300s-ECG-based) RMSSD at rest. Conversely, HR appears method sensitive.

Aerobic exercise requires a redistribution of blood flow to active tissue. The autonomic nervous system contributes to this redistribution of blood flow, which could impact heart rate variability (HRV) following exercise. However, little is known about the impact of exercise intensity and dose on post exercise HRV. The purpose of this study was to investigate HRV following aerobic exercise at different intensities and doses. We hypothesized that higher intensities and doses are associated with lower HRV values following exercise. To address this, 10 recreationally active young adults (5 females, 4 males, age = 28 ± 5 years, BMI = 23.06 ± 2.11 kg/m2) completed a maximal oxygen uptake (VO2max) treadmill test and 3 experimental study days in randomized order where they exercised at 1) 30% VO2max for 30 minutes (30 EX), 2) 70% VO2max for 30 minutes (70 EX), and 3) 70% VO2max for a duration that resulted in energy expenditure equal to the 30 EX visit (70 EXEE). Participants were instrumented with a 3-lead electrocardiogram (ECG) and HRV was measured at 25 minutes and 45 minutes post exercise for all study days. HRV was quantified as the root mean square of successive differences (RMSSD), high frequency (HF) power, low frequency (LF) power, the ratio of LF to HF (LF/HF), and the standard deviation of RR intervals (SDRR). During the post exercise period, heart rate (HR) differed by condition and time (time: P = 0.01, condition: P &lt; 0.01, interaction: P &lt; 0.01) such that HR was lower after 30 EX at both 25 minutes (55 ± 6 bpm) and 45 minutes (57 ± 9 bpm) compared to 70 EX (25 minutes = 73 ± 7 bpm, 45 minutes = 69 ± 4 bpm; P &lt; 0.01 for both). At 25 minutes, HR was lower after 30 EX (55 ± 6 bpm) than 70 EXEE (67 ± 9 bpm; P &lt; 0.01). Post exercise RMSSD differed by condition (time: P = 0.13, condition: P &lt; 0.01, interaction: P &lt; 0.01) such that RMSSD was lower 25 minutes after 70 EX (38 ± 19 ms) compared with 30 EX (95 ± 32 ms; P &lt; 0.01). RMSSD was also lower 45 minutes after 70 EX (41 ± 12 ms) compared with 30 EX (66 ± 23 ms; P ≤ 0.05). RMSSD was lower 25 minutes after 70 EXEE (38 ± 19 ms) compared with 30 EX (95 ± 32 ms, P &lt; 0.05). Post exercise HF power differed by condition and time (time: P &lt; 0.05, condition: P &lt; 0.01, interaction: P = 0.53) such that at 25 min, HF power was lower after 70 EX (893 ± 1300 ms2) compared with 30 EX (4119 ± 2288 ms2; P &lt; 0.01), as well as 70 EXEE (1380 ± 1833 ms2) compared with 30 EX (4119 ± 2288 ms2; P &lt; 0.01). The effect of exercise on SDRR differed by condition and time (time: P &lt; 0.01, condition: P &lt; 0.01, interaction: P = 0.53) such that at 25 min, SDRR was lower after 70 EX (47 ± 22 ms) compared with 30 EX (83 ± 26 ms; P &lt; 0.01), as well as 70 EXEE (50 ± 22 ms) compared with 30 EX (83 ± 26 ms; P &lt; 0.01). There were no differences between study days for post exercise LF or LF/HF ratio (P &gt; 0.05 for all). There were also no differences between 70 EX and 70 EXEE for any measure of HR or HRV (P &gt; 0.05 for all). These results indicate that exercise intensity can independently, and in combination with dose, affect HR and HRV after exercise. Specifically, higher intensity exercise resulted in higher HR and lower HRV 25 minutes after exercise. However, at 45 minutes post exercise, there were dose and intensity interactions only on RMSSD and HR. This implies that intensity is more impactful than dose on HR and HRV following exercise, and that some effects may resolve within 45 minutes of exercise. Funding: Wisconsin Alumni Research Foundation, NIH HL118154 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Bipolar disorder (BD) is a chronic recurrent mood disorder associated with autonomic nervous system (ANS) dysfunction, indexed by heart rate variability (HRV). Changes in HRV between mood states are sparsely studied longitudinally. We aimed to compare HRV of hospitalized manic individuals with their own euthymic selves in a naturalistic observational study. 34 individuals were included, of which 16 were lost to follow-up. Ultimately 15 patients provided reliable heart rate data in both a manic and euthymic state, using photoplethysmography (PPG) sensor wristbands overnight. We calculated HRV measures Root Mean Square of Successive Differences (RMSSD), High-frequency (HF: 0.15-0.40 Hz), Low-frequency (LF: 0.40-0.15 Hz), Very low-frequency (VLF: 0.0033-0.04 Hz), Total power and Sample Entropy in 5-min night-time resting samples. We compared HRV measures by mood state within individuals using paired t-tests and linear regression to control for age and sex. HRV was lower in the manic state when compared to the euthymic state for all HRV metrics (p ≤ 0.02), with large to medium effect sizes (g = 1.24 to 0.65). HRV changes were not significantly affected by age or sex. This longitudinal study provides evidence of lower HRV in manic states compared to euthymia, indicating an association between ANS dysregulation and changes in bipolar mood state. This corroborates previous cross-sectional studies, although the association may be less clear or reversed in hypomanic states. Further investigation in larger longitudinal samples is warranted.

BackgroundReduced heart rate variability (HRV) has been associated with impaired autonomic nervous system (ANS) adaptation, suggesting that HRV could serve as a biomarker for identifying ANS imbalances that may adversely affect an individual's overall health. Many wearable devices used outside medical settings provide measures of HRV, but clinimetric data on their reliability and agreement remain limited. The primary aim of this study was to assess the ability of the Fitbit Versa 4, a consumer-based wearable, to measure nocturnal HRV compared to a reference standard HRV measure obtained from an ambulatory ECG device, the Firstbeat Bodyguard 3.MethodsEight participants simultaneously wore the Fitbit Versa 4 and Firstbeat Bodyguard 3 beginning at least one hour before sleep, throughout their sleep period, and for at least one hour after waking, over a minimum of three nights. HRV was quantified using the root mean square of successive differences (RMSSD). A t-test assessed differences in median HRV between devices, while a Linear Mixed Model and Bland-Altman analysis evaluated relative difference and agreement, respectively.ResultsThe median RMSSD from Fitbit (21.660 ms [15.927, 22.821]) was not significantly different (p = 0.3858) from the median RMSSD from Firstbeat (20.558 ms [13.648, 21.828]. Linear Mixed Model results indicated that, on average, Firstbeat measurements were approximately 92.3% of those obtained from Fitbit.ConclusionsStrong correlation and acceptable agreement between Fitbit Versa 4 HRV measurements and reference standard HRV measurements derived from ECG provide preliminary support for using Fitbit Versa 4 to measure nocturnal HRV outside laboratory settings.

Stress management interventions aim to reduce the disease risk that is heightened by work stress. Possible pathways of risk reduction include improvements in the autonomous nervous system, which is indexed by the measurement of heart rate variability (HRV). A randomized controlled trial on improving stress management skills at work was conducted to investigate the effects of intervention on HRV. A total of 174 lower management employees were randomized into either the waiting list control group (CG) or the intervention group (IG) receiving a 2-day stress management training program and another half-day booster after four and six months. In the trial, 24 h HRV was measured at baseline and after 12 months. Heart rate (HR), root mean square of successive differences (RMSSD), standard deviation of normal-to-normal intervals (SDNN), and standard deviation of the average of normal-to-normal intervals (SDANN) were calculated for 24 h and nighttime periods. Age-adjusted multilevel mixed effects linear regressions with unstructured covariance, time as a random coefficient, and time × group interaction with the according likelihood-ratio tests were calculated. The linear mixed-effect regression models showed neither group effects between IG and CG at baseline nor time effects between baseline and follow-up for SDANN (24 h), SDNN (24 h and nighttime), RMSSD (24 h and nighttime), and HR (24 h and nighttime). Nighttime SDANN significantly improved in the intervention group (z = 2.04, p = 0.041) compared to the control group. The objective stress axis measures (SDANN) showed successful stress reduction due to the training. Nighttime SDANN was strongly associated with minimum HR. Though the effects were small and only visible at night, it is highly remarkable that 3 days of intervention achieved a measurable effect considering that stress is only one of many factors that can influence HR and HRV.

Serotonin and dopamine transporter imaging in patients with obsessive–compulsive disorder

Background: Previous studies have shown that heart rate variability (HRV) analysis is a sensitive indicator of chemotherapy-induced cardiotoxicity. However, most studies to date have observed long-term effects using long-term analyses. The main purpose of this study was to evaluate the acute effect of chemotherapy on the cardiac autonomic nervous system (ANS) in patients with cervical cancer (CC) by examining short-term HRV. Methods: Fifty patients with CC admitted to the Department of Gynecology and Oncology of the First Affiliated Hospital of Bengbu Medical College were enrolled in the study. Based on their chemotherapy regimens, the patients were divided into a DC group (docetaxel + carboplatin) and a TC group (paclitaxel + carboplatin). A 5-min resting electrocardiogram (ECG) was collected before and the day after chemotherapy: the time domain (standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD)) and frequency domain (low-frequency power (LF), high-frequency power (HF), and (LF/HF)) parameters were analyzed, and the differences before and after chemotherapy were compared. Results: The results showed that SDNN, RMSSD and HF were significantly higher in the DC and TC groups after chemotherapy than before (p < 0.05, Cohen's d > 0.5). In addition, LF was significantly higher after TC than before chemotherapy (p < 0.05, Cohen's d > 0.3), and LF/HF was significantly lower after DC than before chemotherapy (p < 0.05, Cohen's d > 0.5). Conclusion: Chemotherapy combining taxane and carboplatin can increase the HRV of CC patients in the short term, and HRV may be a sensitive tool for the early detection of chemotherapy-induced cardiac ANS perturbations.

BackgroundRheumatoid Arthritis (RA) is often associated with autonomic dysfunction, which is presumably playing a role in the pathogenesis of the disease and may contribute to disease activity [1,2]. Accordingly, patients...

Noninvasive assessment of autonomic activity for evaluation of pain in calves, using surgical castration as a model

Heart rate variability (HRV) estimates autonomic nervous system (ANS) influence on the heart and is sex‐specific. Sensory afferents exhibit sex‐specificity; although, there is a paucity of data on the potential effects of Capsaicin, an agonist for transient receptor potential vanilloid channel‐1 (TRPV1), on cardiac ANS activity and if the effect is sex‐dependent. Given the predictive nature of HRV on risk of developing hypertension, understanding the sex differences in factors governing HRV is paramount.PURPOSETherefore, this study sought to determine the sex‐specificity in the effect of capsaicin on cardiac autonomic function estimated through HRV. It was hypothesized that females would have lower HRV than the age‐matched males and that capsaicin could attenuate these sex differences.METHODSHRV was measured in 38 young males (M: n=25) and females (F: n=13), in a blinded crossover design, after acute ingestion of placebo or capsaicin capsules. Resting measurements of HR, RR interval, root mean square of successive differences (RMSSD), natural log‐transformed RMSSD (LnRMSSD), standard deviation of n‐n intervals (SDNN), number of pairs of successive n‐n intervals that differ by more than 50 msec (NN50), and percent NN50 to total n‐n intervals (PNN50) were obtained using standard techniques.RESULTSUnder placebo, males had significantly lower minimum HR (M: 49±9.7 vs. F: 58±16 beats/min, p=0.038, d=‐0.738) and significantly higher NN50 (M: 141±118 vs. F: 33±23, p=0.003, d=‐0.129) than females. There was a main effect of sex on HR (M: 59±9.3 vs. F: 65±12 beats/min, p=0.036, η2=0.098), minimum HR (M: 47±8.3 vs. F: 56±12 beats/min, p=0.014, η2=0.124), and NN50 (M: 177±143 vs. F: 29±17, p&lt;0.001, η2=0.249). There was a significant interaction of sex and treatment (p=0.02, η2=0.027) for RMSSD, where males increased (Placebo: 78±55 vs. Capsaicin: 91±64 ms), and females decreased (Placebo: 105±83 vs. Capsaicin 76±43 ms).CONCLUSIONThis study recapitulates previously documented sex differences in HR and HRV. Acute ingestion of capsaicin increased RMSSD in men, but decreased RMSSD in women, suggesting a sexual dimorphism in parasympathetic response, perhaps due to differences in TRPV1‐sensitive afferents or sensitivity. The physiological ramifications of these findings, specifically in the regulation of blood pressure and ultimately cardiovascular disease risk remain to be explored, especially in the transition to menopause in women.

Background: Low heart rate variability (HRV) is associated with major vascular risk factors for cognitive decline, including hypertension and cardiovascular disease (CVD). Therefore, we hypothesized that higher HRV during mid- to late-life is associated with better cognitive performance. Methods: In a subset of participants from the Multi-Ethnic Study of Atherosclerosis (N = 2,961; aged 45-84 years; 55% female; 40% white, 22% African-American, 25% Hispanic, and 13% Chinese-American), we used multivariate linear regression to study the relationship of short-term HRV to global cognitive performance as measured by the Cognitive Abilities Screening Instrument (CASI; score range 0-100). Two measures of HRV, the standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD), were computed at Exam 1 (2000-2002) and Exam 5 (2010-2012). CASI was administered at Exam 5. Results: In age-, race-, sex- and education-adjusted models, Exam 1 SDNN was significantly associated with performance on the CASI ( β = 0.74 ± 0.22; P &lt; 0.001). This association remained significant after adjustment for cardiovascular risk factors, including prevalent CVD, medication use, and APOE ε4 allele carriage ( β = 0.53 ± 0.23; P = 0.019). Furthermore, participants with highest quartile Exam 1 SDNN scored better than the adjusted mean CASI score (0.61 ± 0.22 points higher; P = 0.022), and 0.81 ± 0.29 points higher than other quartiles ( P = 0.006); participants in other Exam 1 SDNN quartiles scored similarly to each other and to the adjusted mean. In contrast, there were no associations between CASI score and Exam 5 SDNN, Exam 1 RMSSD, or Exam 5 RMSSD after adjustment for cardiovascular risk factors, and no interactions between HRV and race or APOE were present. Conclusions: Highest quartile 10-year antecedent SDNN is associated with better global cognitive performance in a multi-ethnic population of middle-aged and elderly adults, independent of sociodemographic factors, traditional cardiovascular risk factors, APOE status, and prevalent CVD. These results suggest that mid- to late-life HRV may be an early predictor of future cognitive ability.

Therapy with local anesthetics (TLA) is known to provide long-lasting pain relief, raising the question of whether these effects are mediated by changes in autonomic nervous system (ANS) regulation. To address this, we examined alterations in 24-h heart rate variability (HRV) following TLA treatment. Twenty-four patients undergoing TLA and 11 controls were monitored with Holter-ECG over 24 h. HRV parameters including mean heart rate (HR), root mean square of successive differences (RMSSD), stress index (SI), low- and high-frequency power, and total power were calculated in 15-min epochs. Changes were analyzed separately for the day and subsequent night, and the standard deviation of change between consecutive 15-min intervals was introduced as an additional parameter. TLA was associated with significant shifts in HRV within 24 h: HR and SI decreased, whereas RMSSD and low-frequency power increased, with effects most pronounced during the night. Moreover, the variability of changes between epochs was reduced across several parameters, particularly HR, RMSSD, and SI, suggesting a “smoothing” effect in HRV dynamics. These findings indicate that 24-h HRV monitoring can capture autonomic effects of TLA beyond its immediate analgesic action. The reduction of variability in HRV changes introduces a novel metric for assessing ANS modulation, offering new insight into the mechanisms and therapeutic potential of TLA.

Association of lower heart rate variability with neuroimaging markers for dementia‐related pathology: The Multi‐Ethnic Study of Atherosclerosis (MESA)