Comprehensive psychoneuroendocrinology最新文献

Background

Stress can have adverse impacts on health, particularly when it is chronic or resulting from major adverse events. Our study investigated whether relatively common adverse events in older individuals were associated with an increased risk of death, as well as cause-specific death and potential gender differences.

Methods

Participants were 12896 community-dwelling Australians aged ≥70 years at enrolment into the ASPREE (ASPirin in Reducing Events in the Elderly) study and without known life-limiting disease. A questionnaire administered in the year after enrolment, collected information on ten adverse events experienced in the past year. Mortality status was verified by multiple sources including health records and the National Death Index across a maximum of 10 years. Underlying causes of death were determined using clinical information by two adjudicators. Cox-proportional hazards regression models were used to estimate mortality risk.

Results

Two of the ten adverse events were associated with an increased risk of mortality in fully adjusted models. A 69% increased risk of mortality was observed in participants who reported their spouse/partner had recently died (95% CI: 1.19–2.39, P < 0.01). Cancer-related but not cardiovascular deaths also increased. Participants with a seriously ill spouse/partner also had a 23% increased risk of mortality (HR: 1.23, 95% CI: 1.02–1.48, P = 0.03). There was a tendency for these associations to be stronger among men than women.

Limitations

Perceived stress and cortisol were not measured, thus limiting our understanding of the psychological and physiological impacts of adverse events.

Conclusions

Experiencing adverse events in later-life, especially the death of a spouse/partner, may be a risk factor for earlier mortality. These findings may increase public health awareness and better inform initiatives for particular groups, including bereaved men.

More than any other neuropeptide, oxytocin (OXT) is attracting the attention of neurobiologists, psychologists, psychiatrists, evolutionary biologists and even economists. It is often called a “love hormone” due to its many prosocial functions described in vertebrates including mammals and humans, especially its ability to support “bonding behaviour”. Oxytocin plays an important role in female reproduction, as it promotes labour during parturition, enables milk ejection in lactation and is essential for related reproductive behaviours. Therefore, it particularly attracts the interest of many female researchers. In this short narrative review I was invited to provide a personal overview on my scientific journey closely linked to my research on the brain OXT system and the adventures associated with starting my research career behind the Iron Curtain.

Converging, albeit scattered data mainly gathered in animals indicate that the neurotrophin brain-derived neurotrophic factor (BDNF) and the nonapeptide oxytocin (OT) interact in a cooperative way.

Data in humans are really limited and indirect. Therefore, the aim of the present study was to explore the possible existence of a link between OT and BDNF in humans, by means of two peripheral markers, the platelet-poor-plasmatic-BDNF (PPP-BDNF) and the platelet BDNF (PLT-BDNF) and OT levels.

Twenty-six young healthy controls of both sexes who volunteered for the study were included in the study. Fifty ml of peripheral venous blood were drawn from one-night fasting subjects between 8.00 and 9.00 a.m. The BDNF and OT assays were carried out according to common methods. Comparisons for continuous variables were performed by the Student's t-test for variables that follow a normal distribution, and by the Wilcoxon-Mann-Whitney test for variables not normally distributed. The correlations between biological markers were explored by calculating the Pearson's correlation coefficient or Spearman's rank correlation.

The results showed that PLT-BDNF (pg/mg proteins, mean ± SD) and PPP-BDNF (pg/ml, mean ± SD) were 1546 ± 1844 and 10111 ± 1892, respectively. The OT levels (pg/ml, mean ± SD) were 13.92 ± 4.54. The OT levels were significantly higher in women than in men. The Spearman's analysis revealed a statistically significant and negative correlation between OT levels and PLT-BDNF (R = −0.543, p = 0.004).

The findings of this study highlight the presence of a significant and negative correlation between OT and PLT-BDNF in a small group of healthy controls of both sexes. In any case, despite all the limits of peripheral biomarkers, they suggest that this reciprocal influence might have a downstream homeostatic function dampening one activity when the other is activated or no longer necessary, maybe at the level of the stress and/or immune systems.

The mammalian host microbiome affects many targets throughout the body, at least in part through an integrated gut-brain-immune axis and neuropeptide hormone oxytocin. It was discovered in animal models that microbial symbionts, such as Lactobacillus reuteri, leverage perinatal niches to promote multigenerational good health and reproductive fitness. While roles for oxytocin were once limited to women, such as giving birth and nurturing offspring, oxytocin is now also proposed to have important roles linking microbial symbionts with overall host fitness and survival throughout the evolutionary journey.

Background

Children of parents with severe mental illness have several known risk factors for altered pubertal timing. Pubertal timing is important for children’s physical and emotional development. We aimed to examine pubertal timing and associations between pubertal timing, early life adversity and child problem behavior including psychiatric diagnoses among children of parents with schizophrenia or bipolar disorder and controls.

Methods

Self-reported Tanner stage (mean age 11.9, range 10.87–12.67), sex hormone levels, home environment, placement out of home, and problem behavior including psychiatric diagnoses of children at familial high-risk (FHR) of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP) and population-based controls (PBC) were assessed.

Results

A total of 465 children participated in the study (Tanner assessment N = 417, sex hormones N = 293). Assessed with self-reported Tanner, no difference in pubertal timing was found between groups (p = 0.09). Hormone levels did not differ between groups except for inhibin B (mean (SD) = 55.86 (29.13) pg/mL for FHR-SZ girls vs 84.98 (47.98) pg/mL) for PBC girls (p < 0.001)) and for follicle stimulating hormone (FSH) (mean (SD) = 5.82 (1.45) U/L for FHR-BP girls vs 4.54 (1.68) U/L for PBC girls (p < 0.001)). FHR children who were placed out of home (17 children, 3.8% of participants) had higher Tanner stages than those living at home (p < 0.001). Timing was not associated with level of problem behavior or psychiatric diagnoses.

Conclusions

FHR children did not differ from controls in pubertal timing. Early life adversity assessed as placement out of home may be associated with accelerated pubertal timing among children of parents with schizophrenia or bipolar disorder.

The neuropeptide hormone oxytocin is involved in many processes in our bodies, linking our social lives to our internal states. I started out my career studying primate families, an interest that expanded into the role of oxytocin in family-oriented behaviors such as pair bonding and parenting in prairie voles, humans, and other primates. Starting as a post-doc with Dr. C. Sue Carter, I also became interested in the role of oxytocin during development and the way that we manipulate oxytocin clinically. During that post-doc and then as a faculty member at the University of California, Davis, I have worked on a number of these questions.

The improvement of horse welfare through housing conditions has become a real issue in recent years and have highlighted the detrimental effect of individual housing of horses on their health and behaviour. In this new study, we analysed the blood transcriptome of 45 sport horses housed individually that were previously examined for their behaviour and gut microbiota. We performed differential and regression analyses of gene expression, followed by downstream bioinformatic analyses, to unveil the molecular pathways related to the behavioural changes associated with welfare impairment in these sport horses. We found that aggressiveness towards humans was the behavioural indicator the most correlated to blood gene expression and that the pathways involved belonged mainly to systemic inflammation. In contrast, the correlations between genes, alert postures and unresponsiveness towards the environment were weak. When blood gene expression profiling was combined with faecal microbiota of a sub-population of horses, stereotypies came out as the most correlated to blood gene expression. This study shows that aggressiveness towards humans and stereotypies are behavioural indicators that covary with physiological alterations. Further studies are needed regarding the biological correlates of unresponsiveness to the environment and alert postures.

This narrative review charts my unconventional path to becoming a social neuroscientist and describes my research findings – some baffling, some serendipitous, some pivotal – in the field of neuropeptide biology. I trace my childhood as a Bell Labs “brat” to my adolescence as a soccer-playing party girl, to my early days as a graduate student, when I first encountered oxytocin and vasopressin. These two molecules instantly captivated – and held – my attention and imagination. For more than 25 years, a core goal of my research program has been to better understand how these neuropeptides regulate social functioning across a range of species (e.g., meadow voles, mice, squirrel monkeys, rhesus monkeys, and humans), and to translate fundamental insights from this work to guide development of novel pharmacotherapies to treat social impairments in clinical populations. I also discuss my experience of being a woman and a mother in STEM, and identify the important people and events which helped shape my career and the scientist I am today.

Although there is a consistent literature documenting that vagal cardioinhibitory pathways support homeostatic functions, another less frequently cited literature implicates vagal cardioinhibitory pathways in compromises to survival in humans and other mammals. The latter is usually associated with threat reactions, chronic stress, and potentially lethal clinical conditions such as hypoxia. Solving this ‘vagal paradox’ in studies conducted in the neonatal intensive care unit served as the motivator for the Polyvagal Theory (PVT). The paradox is resolved when the different functions of vagal cardioinhibitory fibers originating in two anatomically distinguishable brainstem areas are recognized. One pathway originates in a dorsal area known as the dorsal motor nucleus of the vagus and the other in a ventral area of the brainstem known as nucleus ambiguus. Unlike mammals, in all ancestral vertebrates from which mammals evolved, cardioinhibitory vagal fibers primarily originate in the dorsal motor nucleus of the vagus. Thus, in mammals the vagus nerve is ‘poly’ vagal because it contains two distinct efferent pathways. Developmental and evolutionary biology identify a ventral migration of vagal cardioinhibitory fibers that culminate in an integrated circuit that has been labeled the ventral vagal complex. This complex consists of the interneuronal communication of the ventral vagus with the source nuclei involved in regulating the striated muscles of the head and face via special visceral efferent pathways. This integrated system enables the coordination of vagal regulation of the heart with sucking, swallowing, breathing, and vocalizing and forms the basis of a social engagement system that allows sociality to be a potent neuromodulator resulting in calm states that promote homeostatic function. These biobehavioral features, dependent on the maturation of the ventral vagal complex, can be compromised in preterm infants. Developmental biology informs us that in the immature mammal (e.g., fetus, preterm infant) the ventral vagus is not fully functional and myelinization is not complete; this neuroanatomical profile may potentiate the impact of vagal cardioinhibitory pathways originating in the dorsal motor nucleus of the vagus. This vulnerability is confirmed clinically in the life-threatening reactions of apnea and bradycardia in human preterm newborns, which are hypothetically mediated through chronotropic dorsal vagal pathways. Neuroanatomical research documents that the distribution of cardioinhibitory neurons representing these two distinct vagal source nuclei varies among mammals and changes during early development. By explaining the solution of the ‘vagal paradox’ in the preterm human, the paper highlights the functional cardioinhibitory functions of the two vagal source nuclei and provides the scientific foundation for the testing of hypotheses generated by PVT.

Stress-induced dysregulation of diurnal cortisol is a cornerstone of stress-disease theories; however, observed associations between cortisol, stress, and health have been inconsistent. The reliability of diurnal cortisol features may contribute to these equivocal findings. Our meta-analysis (5 diurnal features from 11 studies; total participant n = 3307) and investigation (15 diurnal cortisol features) in 2 independent studies (St. Louis Personality and Aging Network [SPAN] Study, n = 147, ages 61–73; Minnesota Longitudinal Study of Risk and Adaptation [MLSRA] Study, n = 90, age 37) revealed large variability in the day-to-day test-retest reliability of diurnal features derived from salivary cortisol data (i.e., ICC = 0.00–0.75). Collectively, these data indicate that some commonly used diurnal cortisol features have poor reliability that is insufficient for individual differences research (e.g., cortisol awakening response) while others (e.g., area under the curve with respect to ground) have fair-to-good reliability that could support reliable identification of associations in well-powered studies.