Synergistic antidepressant-like effect of n-3 polyunsaturated fatty acids and probiotics through the brain-gut axis in rats exposed to chronic mild stress.

N-3 polyunsaturated fatty acids (PUFA) and probiotics have antidepressant-like effects, but the underlying mechanisms are unclear. We hypothesized that n-3 PUFA combined with live and dead probiotics synergistically improves depression by modulating the hypothalamic-pituitary-adrenal (HPA) axis and serotonergic pathways through the brain-gut axis. Rats were randomly divided into seven groups (n = 8/group): nonchronic mild stress (CMS) with n-6 PUFA, CMS with n-3 PUFA, n-6 PUFA, live probiotics, dead probiotics, n-3 PUFA, and live probiotics, and n-3 PUFA and dead probiotics. Diets of n-6 and n-3 PUFA and oral supplementation of live and dead probiotics were provided for 12 weeks, and CMS was performed for the last 5 weeks. N-3 PUFA and probiotics improved depressive behaviors and modulated the brain and gut HPA axis by synergistically increasing glucocorticoid receptor expression and decreasing corticotropin-releasing factor expression and blood levels of adrenocorticotropic hormone and corticosterone. N-3 PUFA and probiotics upregulated the brain serotonergic pathway through serotonin levels and expression of brain-derived neurotrophic factor, phosphorylated cAMP response binding protein, and 5-hydroxytryptamine 1A receptor while downregulating the gut serotonergic pathway. Furthermore, n-3 PUFA and probiotics increased the abundance of Ruminococcaceae, brain and gut short chain fatty acid levels, and occludin expression while decreasing the expression of tumor necrosis factor-α, interleukin-1ß, and prostaglandin E2 and blood lipopolysaccharides levels. There was no significant difference between the live and dead probiotics. In conclusion, n-3 PUFA and probiotics had synergistic antidepressant-like effects on the HPA axis and serotonergic pathways of the brain and gut through the brain-gut axis.

N-3 PUFA ameliorated bone loss induced by postmenopausal depression following exposure to chronic mild stress and maternal separation by regulating neuronal processes.

Depression induced by chronic mild stress (CMS) reduced bone mass in ovariectomized (OVX) rats, and maternal separation (MS) during early life aggravated depression-induced bone mass destruction. N-3 polyunsaturated fatty acids (PUFA) have been shown to improve bone mass and depression, but the bone-protecting effects of n-3 PUFA were unclear in CMS+MS-induced depression models. The purpose of this study was to determine whether n-3 PUFA improved CMS+MS-induced postmenopausal bone loss via its antidepressant-like action. Rats were fed diets containing 0% of total energy intake (en %) of n-3 PUFA during lifetime or 1 en % n-3 PUFA during pre-weaning or post-weaning periods, or their entire lifetimes and were allocated to CMS or CMS+MS groups after OVX. Lifetime supply of n-3 PUFA enhanced bone mass and microarchitecture, and expression of runt-related transcription factor 2, while decreasing blood levels of amino-terminal cross-linked telopeptide of type 1 collagen and the expression of receptor activator of nuclear factor kappa Β ligand/osteoprotegerin, activating transcription factor 4, and adrenergic receptor ß2. Lifetime supply of n-3 PUFA decreased levels of adrenocorticotropic hormone and corticosterone and the expression of corticotropin-releasing factor in the brain but increased expression of the glucocorticoid receptor, serotonin-2C receptor, cAMP response element-binding protein (CREB), and calmodulin kinase IV and serotonin levels. Supply of n-3 PUFA during the pre-and post-weaning periods had beneficial effects on the brain but not on the bones. Lifetime supply of n-3 PUFA ameliorated bone loss induced by chronic stress by regulating hypothalamic-pituitary-adrenal axis activity and serotonin-CREB signaling.

Characterizing the postnatal hypothalamic-pituitary-adrenal axis response of in utero heat stressed pigs at 10 and 15 weeks of age.

In utero heat stress alters postnatal physiological and behavioral stress responses in pigs. However, the mechanisms underlying these alterations have not been determined. The study objective was to characterize the postnatal hypothalamic-pituitary-adrenal axis response of in utero heat-stressed pigs. Pigs were subjected to a dexamethasone suppression test followed by a corticotrophin releasing hormone challenge at 10 and 15 weeks of age. Following the challenge, hypothalamic, pituitary, and adrenal tissues were collected from all pigs for mRNA abundance analyses. At 10 weeks of age, in utero heat-stressed pigs had a reduced (P < 0.05) cortisol response to the corticotrophin releasing hormone challenge versus controls. Additionally, the cortisol response tended to be greater overall (P < 0.10) in 15 versus 10-week-old pigs in response to the dexamethasone suppression test. The cortisol response tended to be reduced overall (P < 0.10) in 15 versus 10-week-old pigs in response to the corticotrophin releasing hormone challenge. Hypothalamic corticotropin releasing hormone mRNA abundance tended to be greater (P < 0.10) in in utero heat-stressed versus control pigs at 15-weeks of age. In summary, in utero heat stress altered some aspects of the hypothalamic-pituitary-adrenal axis related to corticotropin releasing hormone signaling, and age influenced this response.

Effectiveness of game-based meditation therapy on neurobiological stress systems in adolescents with posttraumatic symptoms: a randomized controlled trial.

Many adolescents in residential care have experienced traumatic events and suffer from posttraumatic stress. Prolonged activation of neurobiological stress systems as the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis can result in long-lasting maladaptive alternations. This study investigated the effectiveness of Muse, a game-based meditation intervention, on the sympathetic nervous system (SNS), parasympathetic nervous system (PNS), and cortisol basal activity and reactivity to acute stress among adolescents with posttraumatic symptoms in residential care. The intervention consisted of two gameplay sessions a week, for 6 consecutive weeks. Seventy-seven adolescents with clinical levels of posttraumatic symptoms (10-18 years old) received either Muse as an addition to treatment as usual (n = 40) or treatment as usual alone (n = 37). We expected reduced basal activity for the SNS and cortisol and increased basal activity for the PNS. As for the response to acute stress, we expected decreased PNS and increased HPA axis reactivity. The Muse group exhibited lower basal activity for the SNS and increased HPA reactivity to acute stress. There were no differences between conditions on SNS and HPA axis activity during rest and on SNS and PNS reactivity to acute stress. Game-based meditation therapy is a promising intervention for the treatment of adolescents with posttraumatic symptoms in residential care. Implications for clinical relevance and trauma-focused treatment purposes are discussed.

Plasticity of intrinsic excitability across the estrous cycle in hypothalamic CRH neurons.

Stress responses are highly plastic and vary across physiological states. The female estrous cycle is associated with a number of physiological changes including changes in stress responses, however, the mechanisms driving these changes are poorly understood. Corticotropin-releasing hormone (CRH) neurons are the primary neural population controlling the hypothalamic-pituitary-adrenal (HPA) axis and stress-evoked corticosterone secretion. Here we show that CRH neuron intrinsic excitability is regulated over the estrous cycle with a peak in proestrus and a nadir in estrus. Fast inactivating voltage-gated potassium channel (IA) currents showed the opposite relationship, with current density being lowest in proestrus compared to other cycle stages. Blocking IA currents equalized excitability across cycle stages revealing a role for IA in mediating plasticity in stress circuit function over the female estrous cycle.

Hypothalamus volume and DNA methylation of stress axis genes in major depressive disorder: A CAN-BIND study report.

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is considered one of the mechanisms underlying the development of major depressive disorder (MDD), but the exact nature of this dysfunction is unknown. We investigated the relationship between hypothalamus volume (HV) and blood-derived DNA methylation in MDD. We obtained brain MRI, clinical and molecular data from 181 unmedicated MDD and 90 healthy control (HC) participants. MDD participants received a 16-week standardized antidepressant treatment protocol, as part of the first Canadian Biomarker Integration Network in Depression (CAN-BIND) study. We collected bilateral HV measures via manual segmentation by two independent raters. DNA methylation and RNA sequencing were performed for three key HPA axis-regulating genes coding for the corticotropin-binding protein (CRHBP), glucocorticoid receptor (NR3C1) and FK506 binding protein 5 (FKBP5). We used elastic net regression to perform variable selection and assess predictive ability of methylation variables on HV. Left HV was negatively associated with duration of current episode (ρ = -0.17, p = 0.035). We did not observe significant differences in HV between MDD and HC or any associations between HV and treatment response at weeks 8 or 16, overall depression severity, illness duration or childhood maltreatment. We also did not observe any differentially methylated CpG sites between MDD and HC groups. After assessing functionality by correlating methylation levels with RNA expression of the respective genes, we observed that the number of functionally relevant CpG sites differed between MDD and HC groups in FKBP5 (χ2 = 77.25, p < 0.0001) and NR3C1 (χ2 = 7.29, p = 0.007). Cross-referencing functionally relevant CpG sites to those that were highly ranked in predicting HV in elastic net modeling identified one site from FKBP5 (cg03591753) and one from NR3C1 (cg20728768) within the MDD group. Stronger associations between DNA methylation, gene expression and HV in MDD suggest a novel putative molecular pathway of stress-related sensitivity in depression. Future studies should consider utilizing the epigenome and ultra-high field MR data which would allow the investigation of HV sub-fields.

Susceptibility of Women to Cardiovascular Disease and the Prevention Potential of Mind-Body Intervention by Changes in Neural Circuits and Cardiovascular Physiology.

Women have been reported to be more vulnerable to the development, prognosis and mortality of cardiovascular diseases, yet the understanding of the underlying mechanisms and strategies to overcome them are still relatively undeveloped. Studies show that women's brains are more sensitive to factors affecting mental health such as depression and stress than men's brains. In women, poor mental health increases the risk of cardiovascular disease, and conversely, cardiovascular disease increases the incidence of mental illness such as depression. In connection with mental health and cardiovascular health, the presence of gender differences in brain activation, cortisol secretion, autonomic nervous system, vascular health and inflammatory response has been observed. This connection suggests that strategies to manage women's mental health can contribute to preventing cardiovascular disease. Mind-body interventions, such as meditation, yoga and qigong are forms of exercise that strive to actively manage both mind and body. They can provide beneficial effects on stress reduction and mental health. They are also seen as structurally and functionally changing the brain, as well as affecting cortisol secretion, blood pressure, heart rate variability, immune reactions and reducing menopausal symptoms, thus positively affecting women's cardiovascular health. In this review, we investigate the link between mental health, brain activation, HPA axis, autonomic nervous system, blood pressure and immune system associated with cardiovascular health in women and discuss the effects of mind-body intervention in modulating these factors.

Changes in the Hormonal Profile of Athletes following a Combat Sports Performance.

RESULTS: Following fighting, the adrenaline concentration was significantly higher in all athletes, most markedly in K (p < 0.001). Baseline cortisol and BDNF levels did not differ among the groups and rose significantly in all the groups after the performance. Baseline testosterone concentration was slightly higher in K than in JSW and rose in all the groups to reach similar levels; the increase in T was significantly higher than in K. CONCLUSIONS: Despite substantial differences in the characteristics of the combat sports investigated, including the type of physical effort and the required balance between restraint and aggression, the performance in each of them gives rise to similar hormonal changes with a possible exception of karate showing higher stress hormone levels.

FoxO3a suppresses neuropeptide W expression in neuronal cells and in rat hypothalamus and its implication in hypothalamic-pituitary-adrenal (HPA) axis.

FoxO3a, a forkhead family member of transcription factors, is involved in the regulation of cell metabolism, proliferation, differentiation and apoptosis. However, whether FoxO3a participates in the regulation of glucocorticoids induced-hypothalamic-pituitary-adrenal (HPA) dysfunction is still unknown. Our present results indicate that dexamethasone(DEX) increased FoxO3a expression in PC12 and hypothalamic neuronal cultures in correlation to reduced expression of NPW, a process that could be blocked by GR2 antagonist. DEX restrained the phosphorylation of Akt and FoxO3a, but not ERK1/2 phosphorylation, resulting with FoxO3a nuclear localization. Overexpression of FoxO3a inhibited NPW expression, while FoxO3a knockdown by siRNA had the opposite effect. The regulatory region of NPW promoter contains multiple FoxO3a binding sites, and FoxO3a bonding to these sites inhibited its transcriptional activity. In a rat model, chronic administration of corticosterone reduced animals' body weight and sucrose consumption and caused stress- depression like behavior. Corticosterone treatment induced a marked increase in FoxO3a levels, while decreased the expression of NPW protein in the hypothalamus. Immunofluorescent double labeling demonstrated that FoxO3a and NPW were collocated in the hypothalamus. Taken together, these data indicate that NPW is a new direct downstream target gene of FoxO3a. FoxO3a suppressed the transcription of NPW and modulated glucocorticoids-induced HPA dysfunction by directly regulating the expression of NPW. Thus, present findings suggest that FoxO3a and NPW may be potential therapeutic targets for endocrine and psychiatric disorders.

Microbiome and Mental Health, Specifically as It Relates to Adolescents.

PURPOSE OF REVIEW: This article reviews the relationship of the microbiome, the gut-brain axis, and depression. It also will review factors which can influence this relationship, such as chronic stress, medications, and the Western diet typically consumed by adolescents. RECENT FINDINGS: Changes in the gut microbiome increase the release of microbial lipopolysaccharides (LPS) which activate a gut inflammatory response. Gut pro-inflammatory cytokines stimulate the afferent vagal nerve which in turn impacts the hypothalamic-pituitary-adrenal (HPA) axis inducing symptoms associated with depression. Recent research suggests that gut inflammation can induce neuroinflammation which, in turn, stimulates microglia activation and the kynurenine pathway and can activate systemic inflammation-inducing depressive symptoms. Promoting a healthy diet and lifestyle changes, limiting exposure to pesticides, limiting medications that affect the microbiome and the use of such things pre/probiotics and other interventions may complement existing efforts to curb the rise in depression. Alternative and complementary therapies may serve as effective treatments in adolescents with depression.

Impact of acupuncture for allergic rhinitis on the activity of the hypothalamus-pituitary-adrenal axis: study protocol for a randomized controlled trial.

BACKGROUND: Patients with moderate and severe persistent allergic rhinitis (AR) have long-term physical and mental stress, leading to dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis, which results in recurrence of AR. Previous research has proved acupuncture can regulate the function of the neuron-endocrine-immune system and contribute to improving the quality of life of patients with AR. This research aims to investigate the mechanism of acupuncture on the HPA axis in patients with moderate or severe persistent AR. METHODS/DESIGN: This randomized controlled trial aims to study the impact of acupuncture on the HPA axis of patients with moderate and severe AR. This research also aims to compare the curative effects of different treatments in three groups of patients: those receiving western medicine, western medicine and conventional acupuncture, or western medicine and mind-regulating acupuncture. We will study the therapeutic effect of acupuncture and the correlation between the changes of therapeutic indexes and experimental indexes after the treatments. Therapeutic indexes include the Visual Analog Scale (VAS) of nasal symptoms and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) for AR patients; experimental indexes include corticotropin releasing hormone (CRH), adreno-corticotropic hormone (ACTH), cortisol (CORT), interleukin 4 (IL-4), and interferon-γ (IFN-γ). DISCUSSION: The results of this trial will provide evidence for the influence of chronic, long-term, repeated stimulation in patients with moderate and severe persistent AR and the impact of acupuncture on the HPA axis of these patients. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-IOR-16000009 . Registered on 22 August 2016.

Anxiolytic Effect of Essential Oils and Their Constituents: A Review.

Essential oils are usually used in aromatherapy to alleviate anxiety symptoms. In comparison to traditional drugs, essential oils have fewer side effects and more diversified application ways, including inhalation. This review provides a comprehensive overview of studies on anxiolytic effects of essential oils in preclinical and clinical trials. Most of the essential oils used in clinical studies have been proven to be anxiolytic in animal models. Inhalation and oral administration were two common methods for essential oil administration in preclinical and clinical trials. Massage was only used in the clinical trials, while intraperitoneal injection was only used in the preclinical trails. In addition to essential oils that are commonly used in aromatherapy, essential oils from many folk medicinal plants have also been reported to be anxiolytic. More than 20 compounds derived from essential oils have shown an anxiolytic effect in rodents, while two-thirds of them are alcohols and terpenes. Monoamine neurotransmitters, amino acid neurotransmitters, and the hypothalamic-pituitary-adrenal axis are thought to play important roles in the anxiolytic effects of essential oils.

Circadian regulation of endocrine systems.

Hormones are major systemic regulators of homeostatic functions. Not surprisingly, most endocrine signals show some extent of variation across the day. This holds true for the three major hormonal axes of the body originating from the hypothalamus, relayed by the pituitary and terminating in the adrenal (HPA axis), the thyroid (HPT axis), and the gonads (HPG axis), respectively. The rhythmicity of endocrine axis formation has important functions for the maintenance of homeostasis and stabilizes physiological functions against external perturbations. In some cases, such as cortisol, hormonal signals are themselves implicated in circadian regulation and, thus, endocrine disruption may affect the function of the circadian clock network to alter further downstream processes.

A randomised placebo controlled clinical trial on the efficacy of Caralluma fimbriata supplement for reducing anxiety and stress in healthy adults over eight weeks.

BACKGROUND: This study investigated the efficacy of a succulent, Caralluma fimbriata extract (CFE) in reducing anxiety and stress in healthy adults. METHODS: An 8 week double-blind randomised clinical trial, in which 97 adults self-reporting mild to moderate anxiety were given 500 mg b.d. CFE (n = 49), or 500 mg b.d. placebo (n = 48). Anxiety and stress were measured at baseline, week 4, and week 8 to investigate the timing of treatment effect using the GAD-7, Perceived Stress Scale (PSS), Positive and Negative Affect Schedule (PANAS), and salivary cortisol. Data were analysed using mixed ANOVAs on SPSS v.24. RESULTS: Results indicated a significant reduction in anxiety and stress in both groups at week 4 and week 8. The reduction in the CFE group was significantly greater (p < .05) than in the placebo group on the GAD-7 and PSS at week 4 and week 8, and in Negative affect at week 4. Improvement in Positive affect was greater in the CFE group than in the placebo group at week 8. Cortisol analysis indicated that CFE may act through the Hypothalamic-Pituitary-Adrenal (HPA) axis, showing statistically significant changes in males, but not in females. LIMITATIONS: Self-reported instruments involve subjective interpretation thus salivary cortisol was employed as a more objective measure. The study would benefit from a larger sample and longer trial, and the inclusion of a wait-list group to allow comparison between treatment and no treatment. CONCLUSIONS: The findings indicate that CFE is superior to placebo in reducing subclinical anxiety and stress over 8 weeks.

Short-Term d-Aspartic Acid Supplementation Does Not Affect Serum Biomarkers Associated With the Hypothalamic-Pituitary-Gonadal Axis in Male Climbers.

D-aspartic acid (DAA) is promoted as a testosterone (T) enhancing supplement by mechanisms involving the hypothalamic-pituitary-gonadal (HPG) axis. Here, we investigated the short-term effects of DAA on serum biomarkers of the HPG-axis in male climbers. Using a single-blinded, placebo-controlled design, 16 climbers were randomly assigned to either a DAA (3 g/day) or placebo (3 g/day) supplement for 2 weeks. The reverse treatment commenced after a 2-week washout, with all conditions administered in a balanced manner. The subjects maintained their normal weekly training across this study. Serum samples taken before and after each treatment were analyzed for T, luteinizing hormone, sex hormone binding globulin, and cortisol (C), and free T was calculated (cFT). The DAA supplement did not significantly affect serum T, cFT, and luteinizing hormone levels. Only a main effect of time on sex hormone binding globulin (6.8% increase) and C (13.6% decrease) emerged (p < .03). Significant negative associations were identified between pretest values and changes (%) in T, cFT, luteinizing hormone, and C levels with DAA and/or placebo, but these relationships did not differ between treatments (p > .46). Additional measures of physical function and serum hematology also failed to respond to DAA. In summary, a daily dose of DAA during a short training period did not influence T and selected indicators of the HPG-axis in male climbers. Other parameters linked to athletic performance and health status were also unaffected. Our findings support evidence showing that DAA (including DAA-blended supplements) at either recommended or higher dosages does not afford any ergogenic benefits for athletic males.

The impact of an exercise training intervention on cortisol levels and post-traumatic stress disorder in juveniles from an Ugandan refugee settlement: study protocol for a randomized control trial.

BACKGROUND: Latest research demonstrates a significant improvement in stress-related symptoms in psychological disorders as a result of exercise training (ET). Controlled clinical trials further validate the significance of ET by demonstrating lower salivary cortisol levels in patients with post-traumatic stress disorder (PTSD) after intervention. A significant change in cortisol and dehydroepiandrosterone (DHEA) levels can already be found after an 8-12-week ET program. The proposed study aims to investigate the impact of an 8-week ET on PTSD symptoms and changes in cortisol levels in a juvenile refugee sample from the Democratic Republic of the Congo (DRC) at an Ugandan refugee settlement. It is the first to implement an ET intervention in a resource-poor, post-conflict setting. METHODS/DESIGN: In a randomized controlled trial, 198 adolescent participants aged 13-16 years from the DRC who, suffer from PTSD, will be investigated. The participants are based at the Nakivale refugee settlement, an official refugee camp in Uganda, Africa, which is among the largest in the world. The participants will be randomized into an Exercise Training (ET) group with a maximum heart rate (HRmax) of > 60%, an Alternative Intervention (AI) group with low-level exercises, and a Waiting-list Control (WC) group. After the 8-week interventional phase, changes in cortisol awakening response (CAR) and DHEA in the ET group that correspond to an improvement in PTSD symptoms are expected that remain at follow-up after 3 months. DISCUSSION: To date, there is no controlled and reliable longitudinal study examining the effects of an ET program on symptom severity in individuals with PTSD that can be explained with a harmonization of cortisol secretion. The presented study design introduces an intervention that can be implemented with little expenditure. It aims to provide a promising low-threshold and cost-effective treatment approach for the application in resource-poor settings. TRIAL REGISTRATION: German Trials Register, ID: DRKS00014280 . Registered prospectively on 15 March 2018.

Essence of "Shen (Kidney) Controlling Bones": Conceptual Analysis Based on Hypothalamic-Pituitary-Adrenal-Osteo-Related Cells Axis.

As a traditional concept of Chinese medicine (CM), the theory of "Shen (Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen deficiency as a pathological condition has a negative effect on the skeleton of body, specifically the disorder of bone homeostasis. Present studies indicate that Shen deficiency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal (HPA) axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis: cells that comprise bone tissue (osteo-related cells) are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.

Responses of dairy cows with divergent residual feed intake as calves to metabolic challenges during midlactation and the nonlactating period.

Residual feed intake (RFI) is defined as the difference between the actual and expected feed intake required to support animal maintenance and growth. Thus, a cow with a low RFI can obtain nutrients for maintenance and growth from a reduced amount of feed compared with a cow with a high RFI. Variation in RFI is underpinned by a combination of factors, including genetics, metabolism, thermoregulation and body composition; hypothalamic-pituitary-adrenal (HPA) axis responsiveness is also a possible contributor. Responses to 3 metabolic challenges were measured in lactating and nonlactating dairy cattle. Sixteen Holstein Friesian cows with phenotypic RFI measurements that were obtained during the growth period (188-220 d old) were grouped as either low-calfhood RFI (n = 8) or high-calfhood RFI (n = 8). An ACTH (2 µg/kg of body weight), insulin (0.12 U/kg), and epinephrine (a low dose of 0.1 µg/kg and a high dose of 1.6 µg/kg of epinephrine) challenge were each conducted during both midlactation (122 ± 23.4 d in milk) and the nonlactating period (dry period; approximately 38 d after cessation of milking). Cows were housed in metabolism stalls for the challenges and were fed a diet of alfalfa cubes ad libitum for at least 10 d before the experiment (lactating cows also were offered a total of 6 kg of dry matter/d of crushed wheat grain plus minerals fed as 3 kg of dry matter at each milking) and were fasted for 12 h before the challenges. The efficiency of conversion of feed into milk (the ratio of feed consumed to milk produced over the 7 d before the experiment) during midlactation was better (lower) in low-calfhood RFI cows, although dry matter intake did not differ between RFI groups. Low-calfhood RFI cows exhibited a lower plasma cortisol response to the ACTH challenge than high-calfhood RFI cows, particularly in midlactation (-15%). The low-calfhood RFI cows had a greater plasma insulin-like growth factor-1 response to the insulin challenge and plasma fatty acid response to epinephrine compared with the high-calfhood RFI cows. These data suggest that high-calfhood RFI cows exhibit a more responsive HPA axis. As divergence in RFI measured during growth is retained (although reduced) during lactation, it is possible that energy is used to respond to HPA axis activation at the expense of production in high-calfhood RFI dairy cattle during lactation and contributes to a decrease in overall feed use efficiency.

Ancient roots - Modern applications: Mindfulness as a novel intervention for cardiovascular disease.

Cardiovascular disease (CVD) has been associated with chronic psychological stress. Unremittent psychological stress causes dysregulation of the sympathetic nervous system (SNS) and hypothalamic-pituitaryadrenal (HPA) axis, which collectively promotes inflammation, atherosclerosis, and subsequent CVD risk. Stress reduction techniques, such as mindfulness meditation, have been shown to improve some markers of HPA and SNS function at rest and in response to acute stressors, suggesting that such techniques, over time, may be cardioprotective. Therefore, it may be hypothesized that eight weeks of daily mindfulness meditation, compared to a non-mindful relaxation control, may provide a novel strategy to buffer stress responses in healthy and at-risk populations, thereby lowering the risk of chronic psychological stress and the associated CVD risk as measured by arterial stiffness. The current paper outlines methodological considerations for testing this hypothesis, including appropriate acute stressors, and measurement of SNS, HPA axis and cardiovascular function. If the hypothesis is correct, mindfulness meditation would complement healthy lifestyle techniques such as exercise and diet to prevent CVD risk.

Neural - hormonal responses to negative affective stimuli: Impact of dysphoric mood and sex.

BACKGROUND: Maladaptive responses to negative affective stimuli are pervasive, including clinically ill and healthy people, and men and women respond differently at neural and hormonal levels. Inspired by the Research Domain Criteria initiative, we used a transdiagnostic approach to investigate the impact of sex and dysphoric mood on neural-hormonal responses to negative affective stimuli. METHODS: Participants included 99 individuals with major depressive disorder, psychosis and healthy controls. Functional magnetic resonance imaging (fMRI) was complemented with real-time acquisition of hypothalamo-pituitary-adrenal (HPA) and -gonadal (HPG) hormones. fMRI data were analyzed in SPM8 and task-related connectivity was assessed using generalized psychophysiological interaction. RESULTS: Across all participants, elevated cortisol response predicted lower brain activity in orbitofrontal cortex and hypothalamus-amygdala connectivity. In those with worse dysphoric mood, elevated cortisol response predicted lower activity in hypothalamus and hippocampus. In women, elevated cortisol response was associated with lower activity in medial prefrontal cortex and low hypothalamo-hippocampal connectivity. In women with high dysphoric mood, elevated cortisol response was associated with low hypothalamo-hippocampal connectivity. There were no interactions with diagnosis or medication. LIMITATIONS: There was limited power to correct for multiple comparisons across total number of ROIs and connectivity targets; cortisol responses were relatively low. CONCLUSIONS: We conclude that the pathophysiology in neural-hormonal responses to negative affective stimuli is shared across healthy and clinical populations and varies as a function of sex and dysphoric mood. Our findings may contribute to the development of hormonal adjunctive therapeutics that are sex-dependent, underscoring the importance of one's sex to precision medicine.