Contemporary theories of early development and emerging child psychopathology all posit a major, if not central role for physiological responsiveness. To understand infants’ potential risk for emergent psychopathology, consideration is needed to both autonomic reactivity and environmental contexts (e.g., parent–child interactions). The current study maps infants’ arousal during the face-to-face still-face paradigm using skin conductance (n = 255 ethnically-diverse mother–infant dyads; 52.5% girls, mean infant age = 7.4 months; SD = 0.9 months). A novel statistical approach was designed to model the potential build-up of nonlinear counter electromotive force over the course of the task. Results showed a significant increase in infants’ skin conductance between the Baseline Free-play and the Still-Face phase, and a significant decrease in skin conductance during the Reunion Play when compared to the Still-Face phase. Skin conductance during the Reunion Play phase remained significantly higher than during the Baseline Play phase; indicating that infants had not fully recovered from the mild social stressor. These results further our understanding of infant arousal during dyadic interactions, and the role of caregivers in the development of emotion regulation during infancy.

The etiology of psychopathology is multifaceted and warrants consideration of factors at multiple levels and across developmental time. Although experiences of adversity in early life have been associated with increased risk of developing psychopathology, pathways toward maladaptation or resilience are complex and depend upon a variety of factors, including individuals’ physiological regulation and cognitive functioning. Therefore, in a longitudinal cohort of 113 mother–child dyads, we explored associations from early adverse experiences to physiological coregulation across multiple systems and subsequent variations in executive functioning. Latent profile analysis derived multisystem profiles based on children's heart rate, respiratory sinus arrhythmia, pre-ejection period, and cortisol measured during periods of rest and reactivity throughout a developmentally challenging protocol. Three distinct profiles of multisystem regulation emerged: heightened multisystem baseline activity (anticipatory arousal/ autonomic nervous system [ANS] responder), typically adaptive patterns across all systems (active copers/mobilizers), and heightened hypothalamic–pituitary–adrenal (HPA) axis activity (HPA axis responders). Path models revealed that children exposed to adversity before 18 months were more likely to evidence an anticipatory arousal/ANS responders response at 36 months, and children in this profile had lower executive functioning scores than the active copers/mobilizers. In sum, these findings provide important information about potential physiological associations linking early adversity to variations in children's task-based executive functioning.

We evaluated whether the association between deviant peer affiliation and onset of substance use is conditional upon sex and sympathetic nervous system (SNS) reactivity as measured by pre-ejection period (PEP). Community-sampled adolescents (N = 251; M = 15.78 years; 53% female; 66% White, 34% Black) participated in three waves. PEP reactivity was collected during a mirror star-tracer stress task. Alcohol, marijuana, tobacco, or any substance use, as well as binge drinking and sexual activity involving substance use were outcomes predicted by affiliation with deviant peers and two- and three-way interactions with sex and PEP reactivity. Probability of substance use increased over time, but this was amplified for adolescents with greater deviant peer affiliation in conjunction with blunted PEP reactivity. The same pattern of results was also found for prediction of binge drinking and sexual activity involving substance use. Findings are discussed in the context of biosocial models of adolescent substance use and health risk behaviors.

Children who spend their early lives in institutions experience profound psychosocial deprivation that is associated with altered stress response system development. Here, we used data from a longitudinal randomized controlled trial of foster care for institutionally reared children to examine whether caregiving quality and stressful life events (SLEs) in early adolescence (age 12) influence patterns of hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system (SNS) reactivity. Controlling for the effect of institutional care, higher caregiving quality at age 12 was associated with heightened cortisol and SNS reactivity. However, moderation analysis revealed that the latter effect was only observed among never-institutionalized children, whereas ever-institutionalized children demonstrated a persistently blunted SNS response regardless of recent caregiving quality. Among institutionally reared children, SLEs interacted with prior random assignment to foster care, such that those placed in foster care early in development had a SNS response that approximated never-institutionalized children when SLEs at age 12 were low. In contrast, SNS reactivity was persistently blunted among those with prolonged deprivation, regardless of recent SLEs. Early-life deprivation is associated with persistent blunting of stress response systems, but normalization may be achievable if SLEs are limited following placement into enriched family-based care.

Sleep-disordered breathing (SDB) worsens over pregnancy, and obstructive sleep apnea is associated with serious maternal complications. Intrauterine exposures that provoke insulin resistance (IR), inflammation, or oxidative stress may have long-term offspring health consequences. In obesity, worsening maternal SDB appears to be an exposure that increases the risk for both small- or large-for-gestational-age (SGA, LGA, respectively), suggesting distinct outcomes linked to a common maternal phenotype. The aim of this paper is to systematically review and link data from both mechanistic rodent models and descriptive human studies to characterize the impact of maternal SDB on fetal development. A systematic review of the literature was conducted using PubMed, Embase, and CINAHL (01/2000–09/2019). Data from rodent (9 studies) and human models (48 studies, 5 meta-analyses) were included and reviewed using PRISMA guidelines. Evidence from rodent models suggests that intermittent maternal hypoxia results in mixed changes in birth weight (BW) followed by accelerated postnatal growth, while maternal sleep fragmentation results in normal BW followed by later metabolic derangement. Human studies support that maternal SDB is associated with both SGA and LGA, both of which may predispose offspring to later obesity. Evidence also suggests a link between SDB, inflammation, and oxidative stress that may impact maternal metabolism and/or placental function. SDB is common in pregnancy and affects fetal growth and development. Given that SDB has significant potential to adversely influence the intrauterine metabolic environment, larger, prospective studies in humans are urgently needed to fully elucidate the effects of this exposure on offspring metabolic risk.

Changes in cardiac autonomic regulation, expressed by increased sympathetic activity and decreased heart rate variability, have an important relationship with the onset of lethal cardiac phenomena. Therefore, we aimed to evaluate the cardiac autonomic behaviour in young people according to their level of physical activity. Through the International Physical Activity Questionnaire, 55 healthy young non-smokers with no history of previous diseases and whose parents did not suffer from metabolic syndrome were assessed and divided into groups: sedentary (n=12), insufficiently active (n=16), active (n=14), and very active (n=13). We collected respiratory rate, systolic and diastolic blood pressure at rest, and body mass index. Subjects remained supine at rest, and without mental stress for 15 minutes in a controlled environment. Using a cardiofrequency meter (Polar® RS800CX), data were analysed in the time domain, frequency domain, and detrended fluctuation analysis. For the sedentary group, the mean RR and rMSSD were significantly lower, and the insufficiently active group showed higher means, but significantly only for rMSSD. The insufficiently active group showed in the detrended fluctuation analysis that α2 was significantly lower compared with the sedentary, active, and very active groups. We conclude that young, healthy, sedentary individuals present an increased heart rate and that insufficiently active individuals present a decreased fractal correlation and increased parasympathetic activity.

The aim of the study was to prospectively evaluate the association between the occurrence of post-traumatic stress disorder (PTSD) and the adrenergic response to the traumatic event, and additionally, to explore the link between PTSD and the initial norepinephrine:cortisol ratio. Plasma levels and urinary excretion of norepinephrine (NE) were measured in 155 survivors of traumatic events during their admission to a general hospital emergency room (ER) and at 10 d, 1 month and 5 months later. Symptoms of peri-traumatic dissociation, PTSD and depression were assessed in each follow-up session. The Clinician-Administered PTSD Scale (CAPS) conferred a diagnosis of PTSD at 5 months. Trauma survivors with (n=31) and without (n=124) PTSD had similar levels of plasma NE, urinary NE excretion, and NE:cortisol ratio in the ER. Plasma NE levels were lower in subjects with PTSD at 10 d, 1 month, and 5 months. There was a weak but significant positive correlation between plasma levels of NE in the ER and concurrent heart rate, and a negative correlation between NE in the ER and dissociation symptoms. Peripheral levels of NE, shortly after traumatic events, are poor risk indicators of subsequent PTSD among civilian trauma victims. Simplified biological models may not properly capture the complex aetiology of PTSD.

While investigating the reversible seasonal obesity of Siberian hamsters, direct sympathetic nervous system (SNS) postganglionic innervation of white adipose tissue (WAT) has been demonstrated using anterograde and retrograde tract tracers. The primary function of this innervation is lipid mobilization. The brain SNS outflow to WAT has been defined using the pseudorabies virus (PRV), a retrograde transneuronal tract tracer. These PRV-labelled SNS outflow neurons are extensively co-localized with melanocortin-4 receptor mRNA, which, combined with functional data, suggests their involvement in lipolysis. The SNS innervation of WAT also regulates fat cell number, as noradrenaline inhibits and WAT denervation stimulates fat cell proliferation in vitro and in vivo respectively. The sensory innervation of WAT has been demonstrated by retrograde tract tracing, electrophysiological recording and labelling of the sensory-associated neuropeptide calcitonin gene-related peptide in WAT. Local injections of the sensory nerve neurotoxin capsaicin into WAT selectively destroy this innervation. Just as surgical removal of WAT pads triggers compensatory increases in lipid accretion by non-excised WAT depots, capsaicin-induced sensory denervation triggers increases in lipid accretion of non-capsaicin-injected WAT depots, suggesting that these nerves convey information about body fat levels to the brain. Finally, parasympathetic nervous system innervation of WAT has been suggested, but the recent finding of no WAT immunoreactivity for the possible parasympathetic marker vesicular acetylcholine transporter (VAChT) argues against this claim. Collectively, these data suggest several roles for efferent and afferent neural innervation of WAT in body fat regulation.

Sympathetic stimulation has long been recognized to mobilise fatty acids from white adipose tissue. However, it is now apparent that adipose tissue is not only concerned with energy storage as fat, but is a major endocrine and secretory organ. This change has resulted from the identification of leptin as a hormone of energy balance secreted by white adipose tissue. The sympathetic system is a key regulator of leptin production in white fat. Sympathomimetic amines, cold exposure or fasting (which lead to sympathetic stimulation of white fat), decrease ob gene expression in the tissue and leptin production. On the other hand, sympathetic blockade often increases circulating leptin and ob gene expression, and it is postulated that the sympathetic system has a tonic inhibitory action on leptin synthesis. In rodents this action is through stimulation of b3-adrenoceptors. The adrenal medulla (as opposed to the direct sympathetic innervation) has been thought to play only a minor role in the catecholaminergic regulation of white adipose tissue. However, in rodents responses of the leptin system to adrenergic blockade vary with the method used. Changes in leptin and ob gene expression are considerably less using methods of blockade that only effect the terminal adrenergic innervation, rather than medullary secretions as well. Stimulation of the leptin system increases sympathetic activity and hence metabolic activity in many tissues. As well as leptin, other (but not all) secretions from white adipose tissue are subject to sympathetic regulation. In obesity the sympathetic sensitivity of adipose tissue is reduced and this factor may underlie the dysregulation of leptin production and other adipose tissue secretions.

Whilst a number of neuroendocrine afferent signals are implicated in body-weight homeostasis, the major efferent pathway is the sympathetic nervous system (SNS), which affects both energy expenditure and substrate utilization. Thyroid hormones and their interactions with the SNS may also have a role to play. Some of the variability in resting energy expenditure can be explained by differences in SNS activity, and β-blockade can reduce energy expenditure and diet-induced thermogenesis in Caucasians. Excess energy intake leads to SNS activation and increased diet-induced thermogenesis. A relationship has also been demonstrated between spontaneous physical activity and SNS activity. In many animal models the SNS activates brown adipose tissue thermogenesis, hence increasing diet-induced thermogenesis and dissipating excess energy as heat. This effect is mediated via β3-adrenoceptors and activation of an uncoupling protein unique to brown adipose tissue. Homologous proteins have been identified in human tissues and may play a role in human energy expenditure. How the SNS is implicated in this process is unclear at present. β3-Adrenoceptor polymorphism has been associated both with lower resting energy expenditure in some populations and with reduced autonomic nervous system activity. SNS effects on substrate cycling may also play a role. In the development of obesity the effects of the SNS in promoting lipolysis and fat oxidation are likely to be at least as important as its effects on thermogenesis. β-Blockade has relatively small effects on energy expenditure, but more pronounced effects on reducing lipid oxidation, so tending to favour fat storage and weight gain. Low lipid oxidation is a risk factor for weight gain, and there is some evidence that low basal sympathetic nerve activity in muscle is associated with this process. Overall, the relationship between SNS activity and obesity is complex, with evidence of low SNS activity occurring in some, but not all, studies.

Summary

Background and objectives: The aim of this prospective, randomized, double-blind study was to determine the effects of adding two different target-controlled concentrations of remifentanil (1 and 3 ng mL−1) on the desflurane requirement for blunting sympathetic responses after surgical incision (minimum anaesthetic concentration (MACBAR)). Methods: 67 patients, aged 20–50 yr, ASA I, undergoing general anaesthesia for elective abdominal surgery were enrolled and randomly allocated to receive no remifentanil infusion (n = 21) or a target-controlled effect-site concentration of 1 ng mL−1 (n = 24) or 3 ng mL−1 remifentanil (n = 22). All patients were anaesthetized with propofol, cisatracurium and desflurane with a mixture of 60% nitrous oxide in oxygen. Sympathetic responses to surgical incision were determined after a 20-min period of stable end-tidal desflurane and target-controlled remifentanil concentrations. Predetermined end-tidal desflurane concentrations and the MACBAR for each group were determined using an up-and-down sequential-allocation technique. Results: The MACBAR of desflurane was higher in the group receiving no remifentanil (6.25% [95% confidence interval: 5.9–6.5%]) as compared with patients of the groups receiving 1 ng mL−1 (2.7% [2.6–2.8%]; P < 0.001) and 3 ng mL−1 remifentanil (2% [1.9–2.2%]; P < 0.01). When considering a MAC value in this age population and the contribution of 60% nitrous oxide (0.55 MAC), the combined MACBAR values, expressed as multiples of the MAC, were 1.9, 0.8 and 0.6 MAC, in the three groups, respectively. Conclusion: A target-controlled concentration of 1 ng mL−1 remifentanil results in a 57% decrease in the MACBAR of desflurane combined with 60% nitrous oxide. Increasing the target concentration of remifentanil to 3 ng mL−1 produces a further 26% decrease in the MACBAR values of desflurane.

Summary

Background and objective: Desflurane has been shown to increase sympathetic activity and heart rate (HR) in a concentration-dependent manner. Nevertheless, desflurane, like all other volatile anaesthetics, increased HR in parallel to vagal inhibition in a previous study. Therefore, our hypothesis is that desflurane elicits tachycardia by vagal inhibition rather than by activation of the sympathetic nervous system.

Methods: Six dogs were studied awake and during desflurane anaesthesia (1 and 2 MAC) alone, after pre-treatment with propranolol (2 mg kg−1 followed by 1 mg kg−1 h−1), or after pre-treatment with atropine (0.1 mg kg−1 followed by 0.05 mg kg−1 h−1). The effects on HR and HR variability were compared by an analysis of variance (P < 0.05). HR variability was analysed in the frequency domain as power in the high-(0.15–0.5 Hz, vagal activity) and low-frequency range (0.04–0.15 Hz, sympathetic and vagal activity).

Results: HR increased during 2 MAC of desflurane from about 60 (awake) to 118 ± 2 beats min−1 (mean ± SEM) in controls and to 106 ± 3 beats min−1 in dogs pre-treated with propranolol. In contrast, pre-treatment with atropine increased HR from 64 ± 2 to 147 ± 5 beats min−1 (awake) and HR decreased to 120 ± 5 beats min−1 after adding desflurane. High-frequency power correlated inversely with HR (r2 = 0.95/0.93) during desflurane alone and in the presence of β-adrenoceptor blockade, with no significant difference between regression lines. There was no correlation between these variables during atropine/desflurane.

Conclusions: The increase in HR elicited by desflurane mainly results from vagal inhibition and not from sympathetic activation.

This study examined possible neuroendocrine mechanisms underlying the association between stress and antibody response to vaccination. Hepatitis B antibody titers were obtained, and salivary cortisol and cardiovascular activity measured during baseline, mental arithmetic, and recovery in 30 undergraduates. It was hypothesised that higher reactivity would be associated with poorer antibody status. Compared to individuals with high antibody titers, those with low titers had significantly lower cortisol levels throughout, exhibited a significantly attenuated end-of-task reduction in cortisol relative to resting baseline, and had larger cardiac output and inotropic reactions, but smaller increases in total peripheral resistance, to mental arithmetic. In sum, variations in indices of both hypothalamic pituitary adrenocortical axis and sympathetic nervous system activity were associated with individual differences in immune response to vaccination.

Granular cell tumour is a rare neoplasm that can occur in various sites. This report describes a 48-year-old female with a malignant granular cell tumour originating from the cervical sympathetic nerve trunk, who presented with hyperaesthesia of the left shoulder. The tumour had a maximum diameter of 86 mm and involved adjacent tissues directly.

Histopathologically, it showed considerable variation in the size and shape of nuclei, with occasional mitosis and an abundant granular cytoplasm. Immunohistochemically, the tumour reacted positively for S-100 protein and neuron-specific enolase, indicating its neural origin. Following total local excision of the lesion, the patient has been well without recurrence.