The dexamethasone suppression test as a biomarker for suicidal behavior: A systematic review and meta-analysis.

BACKGROUND: The dexamethasone suppression test (DST), which measures HPA-axis functioning, is a potential biomarker for suicidal behavior. The current study aimed (a) to synthesize available knowledge on the association between DST non-suppression and suicidal behavior, and (b) to study potential moderators. METHODS: A total of 4236 studies were screened, 43 were included. Suicide attempts and suicide completion were studied separately. The meta-analysis included 37 effect sizes for suicide attempts (n = 3733) and 11 effect sizes for suicide completion (n = 1626). RESULTS: DST non-suppression was associated with completed suicide (odds ratio (OR) = 2.10, (95 % CI [1.37, 3.23]). For suicide attempts, we found no evidence that DST status was associated in the overall meta-analysis including all patient samples. However, moderator analysis indicated that the DST status was associated with suicide attempts in patient samples that included psychopathology other than just mood disorders, such as psychotic, substance use and personality disorders (OR = 2.34, 95 % CI [1.39-3.93], k = 11). LIMITATIONS: The potential influence of publication bias and exclusion of some relevant published studies (since effect sizes could not be calculated, authors could not supply data or authors could not be reached) are limitations. Furthermore, missing moderator data decreased our ability to explain heterogeneity between studies. CONCLUSIONS: The results of this meta-analysis support the hypothesis that DST non-suppression is predictive of suicidal behavior. More research is needed to investigate optimal cut-off values, confounding factors and the potential usefulness of the DST in clinical practice in terms of personalized medicine.

NMC-4 Ameliorates Depression-Like Behavior and Neuroinflammation Caused by Chronic Unpredictable Mild Stress.

Depression is a prevalent mental disorder, but the side effects of antidepressants also make depressed patients resistant. Effective and safe antidepressants should be developed from traditional herbs, with the aim of reducing the side effects of antidepressants and improving the efficacy of drugs. In this study, the new macamide compound-4 (NMC-4) was synthesized for the first time, addressing the problem of difficult extraction, isolation, and low content of natural macamide. NMC-4 was characterized using mass spectrometry, nuclear magnetic resonance, and infrared spectroscopy. The protective effect of NMC-4 against cell injury was demonstrated to be stronger than that of natural macamide (N-benzylhexadecanamide, XA) using a PC12 cell injury model. The study explored the effects of NMC-4 on chronic unpredictable mild stress (CUMS)-induced depressive symptoms. NMC-4 significantly improved depressive-like behaviors. NMC-4 ameliorated CUMS-induced depressive-like behaviors by mitigating neuroinflammation and modulating the NF-κB/Nrf2 and BDNF/PI3K/Akt pathways.

High rates of mood disorders in patients with chronic idiopathic eosinopenia.

Background: Mood disorders (MD) are multifactorial disorders. Identifying new biomarkers for the early diagnosis of MD and predicting response to treatment is currently a significant research topic. Both eosinopenia and MD are associated with increased activity of the hypothalamic-pituitary-adrenal axis. The present study, therefore, used a clear definition of chronic idiopathic eosinopenia (CIE) to determine the rate of MD in a large cohort of individuals with CIE. Methods: This retrospective population-based, case-control study uses data of seven consecutive years from the database of Leumit Health Services (LHS) - a nationwide health maintenance organization in Israel. Results: Participants were 13928 LHS members with CIE and 27858 negative controls. The CIE group exhibited significantly higher rates of MD than the control group throughout the whole study period, except for atypical depressive disorder at baseline. Conclusions: CIE might be associated with a higher prevalence of MD. Further basic research should elucidate the pathophysiologic mechanisms linking CIE and MD.

Critical illness-related corticosteroid insufficiency: latest pathophysiology and management guidelines.

Intensive care unit (ICU) admissions in the United States exceed 5.7 million annually, often leading to complications such as post-intensive care syndrome and high mortality rates. Among these challenges, critical illness-related corticosteroid insufficiency (CIRCI) requires emphasis due to its complex, multiple-cause pathophysiology and varied presentations. CIRCI, characterized by adrenal insufficiency during critical illness, presents in up to 30% of ICU patients and may manifest as an exaggerated inflammatory response. Factors such as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, tissue corticosteroid resistance, and drug-induced suppression contribute to CIRCI. Diagnosis is a complex process, relying on a comprehensive assessment including clinical presentation, laboratory findings, and dynamic stimulatory testing. Treatment involves intensive medical care and exacting glucocorticoid therapy. Recent guidelines advocate for individualized approaches tailored to patient presentation and etiology. Understanding the pathophysiology and treatment of CIRCI is vital for clinicians managing critically ill patients and striving to improve outcomes. This research paper aims to explore the latest developments in the pathophysiology and management of CIRCI.

Exploring the associations between momentary cortisol levels and psychotic-like experiences in young adults: Results from a temporal network analysis of daily-life data.

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of psychosis and subthreshold psychotic symptoms commonly referred to as psychotic-like experiences (PLEs). The exact mechanisms linking the HPA axis responses with the emergence of PLEs remain unknown. The present study aimed to explore real-life associations between stress, negative affect, salivary cortisol levels (a proxy of the HPA axis activity) as well as PLEs together with their underlying cognitive biases (i.e., threat anticipation and aberrant salience). The study was based on the experience sampling method scheduled over 7 consecutive days in the sample of 77 drug-naïve, young adults (18-35 years). The saliva samples were collected with each prompt to measure cortisol levels. A temporal network analysis was used to explore the directed associations of tested variables. Altogether, 3234 data entries were analyzed. Data analysis revealed that salivary cortisol levels did not directly predict next-moment fluctuations of PLEs. However, higher salivary cortisol levels were associated with higher next-moment levels of PLEs through the effects on threat anticipation and negative affect. In turn, PLEs appeared to predict cortisol levels through the effects on negative affect and event-related stress. Negative affect and threat anticipation were the most central nodes in the network. There might be bidirectional associations between the HPA axis responses and PLEs. Threat anticipation and negative affect might be the most important mediators of these associations. Interventions targeting these mediators might hold promise for disrupting the connection between the HPA axis dysregulation and PLEs.

Systemic Adverse Events Associated with Locally Administered Corticosteroids.

Topical corticosteroids are a mainstay in the treatment of many pediatric disorders. While they have proven beneficial therapeutic effects and are generally considered safe, systemic adverse events may occur. This study presents four cases of children who experienced systemic adverse events after using inhaled and intranasal topical corticosteroids, as well as topical corticosteroids in other forms. A comprehensive literature review was performed to explore the existing evidence on this topic. The aim of this study is to raise awareness among healthcare providers about the possibility of systemic adverse events associated with the use of locally administered corticosteroids in pediatric patients. This information underscores the importance of careful monitoring, individualized treatment plans, and further research to better understand and mitigate the risks associated with corticosteroids, even those not given systemically.

Influence of footshock number and intensity on the behavioral and endocrine response to fear conditioning and cognitive fear generalization in male rats.

Foot-shock paradigms have provided valuable insights into the neurobiology of stress and fear conditioning. An extensive body of literature indicates that shock exposure can elicit both conditioned and unconditioned effects, although delineating between the two is a challenging task. This distinction holds crucial implications not only for the theoretical interpretation of fear conditioning, but also for properly evaluating putative preclinical models of post-traumatic stress disorder (PTSD) involving shock exposure. The characteristics of shocks (intensity and number) affect the strength of learning, but how these characteristics interact to influence conditioned and unconditioned consequences of shocks are poorly known. In this study, we aimed to investigate in adult male rats the impact of varying shock number and intensity on the endocrine and behavioral response to contextual fear conditioning and fear generalization to a novel environment markedly distinct from the shock context (i.e., fear generalization). Classical biological markers of stress (i.e., ACTH, corticosterone, and prolactin) were sensitive to manipulations of shock parameters, whereas these parameters had a limited effect on contextual fear conditioning (evaluated by freezing and distance traveled). In contrast, behavior in different novel contexts (fear generalization) was specifically sensitive to shock intensity. Notably, altered behavior in novel contexts markedly improved, but not completely normalized after fear extinction, hypoactivity apparently being the result of both conditioned and unconditioned effects of foot-shock exposure. The present results will contribute to a better understanding of shock exposure as a putative animal model of PTSD.

Hominis Placenta modulates PTSD-like behaviors in SPSS-induced PTSD mice: Regulating energy metabolism and neuronal activity.

The symptoms of post-traumatic stress disorder (PTSD) include re-experiencing trauma, avoidance behaviors, negative alterations in cognition and mood. However, the underlying molecular mechanisms are unclear. Dysfunction of hypothalamic-pituitary-adrenal axis (HPA-axis) and dysregulation of glutamatergic and GABAergic systems were shown during PTSD. Therefore, regulating hormonal change or glutamate energy metabolism are considered as a therapeutic approach to alleviate this condition. Herbal medicine may be effective in treating PTSD due to its ability to target multiple underlying mechanisms with various compounds. Hominis placenta (HP) is a traditional medicine widely used in East Asia for various conditions. However, the effect on PTSD has not been clarified. We aimed to investigate the effects of HP treatment in single-prolonged stress with shock (SPSS)-induced PTSD mice and explore its possible mechanisms. HP treatment at ST36 acupoints, combined with herbal medicine and acupuncture point stimulation, was applied three times/week for 2 weeks. HP treatment effectively alleviated anxiety and cognitive decline in SPSS-induced PTSD mice, as detected by Open field and the Y-maze test. Additionally, HP decreased the corticosterone levels and proinflammatory cytokines in the serum, modulated brain energy metabolism, and inhibited glutamate excitotoxicity, while regulating neuronal activity through modulating brain-derived neurotrophic factor (BDNF) levels, as demonstrated by western blot and immunohistochemistry, and flow cytometry analyses. These findings reveal that HP treatment effectively alleviates PTSD-like behaviors by regulating energy metabolism and neuronal activity though modulation of the HPA-axis and BDNF levels in PTSD mice, indicating that HP treatment is a promising therapeutic approach for PTSD.

General Anesthesia for Patients With Cyclic Vomiting Syndrome and Obesity: A Case Report.

Cyclic vomiting syndrome (CVS) is a chronic digestive disorder characterized by recurrent episodes of severe nausea and vomiting. The perioperative management of patients with CVS undergoing general anesthesia is challenging, especially when combined with obesity. This case report describes the successful management of a patient with CVS and obesity who underwent dental surgery under general anesthesia. A 21-year-old woman with CVS, obesity (body mass index, 35), and intellectual disability was scheduled for tooth extraction and composite resin restoration under general anesthesia. The patient was diagnosed with CVS at the age of 20 years with frequent vomiting attacks requiring hospitalization. Surgery was scheduled during the CVS remission to reduce the risk of perioperative vomiting. Preoperative laboratory test results were normal, including serum adrenocorticotropic hormone (ACTH), anti-diuretic hormone (ADH), and cortisol levels. General anesthesia was induced using remifentanil and propofol. Nasal endotracheal intubation was performed after rocuronium administration. Local anesthesia (2% lidocaine with 1:80,000 epinephrine) was used for all dental procedures. Postoperatively, midazolam was administered to control agitation. No postoperative vomiting occurred. Serum ACTH, ADH, and cortisol levels showed no significant changes before and after anesthesia, suggesting that hypothalamic-pituitary-adrenal (HPA) axis activation due to surgical stress did not occur. This case highlights the importance of careful perioperative planning and monitoring stress-related hormone levels in patients with CVS or obesity. An anesthetic approach using midazolam may effectively suppress HPA axis activation and prevent postoperative vomiting.

Comparison of CUMS at different pregnancy stages, maternal separation, and their effects on offspring in postpartum depression mouse models.

Due to the diversity of postpartum depression (PPD) patients and the complexity of associated pathophysiological changes, most current animal models cannot accurately simulate PPD-like symptoms. In this study, we established a reliable animal model for PPD by inducing chronic unpredictable mild stress (CUMS) at different stages (pre-pregnancy, pregnancy, or postnatal) in female mice, followed by maternal separation (MS) from day 2-21 after delivery. The results for female mice subjected to pre-pregnancy stress were not statistically significant due to a lower conception rate. However, female mice exposed to CUMS during either the gestational or postnatal stage, followed by MS, successfully exhibited PPD-like symptoms. The models were deemed effective based on observed behavioral abnormalities, impaired hippocampal neuron functioning, and reduced serum concentrations of neurotransmitters (5-HT, GABA, and NE). Additionally, mice that underwent gestational CUMS followed by MS displayed a more dysfunctional hypothalamic-pituitary-adrenal (HPA) axis and more severe uterine inflammation. The study also investigated the impact of PPD on the behavior and neurodevelopment of adolescent offspring through behavioral tests, enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, and western blotting (WB). The results indicated that adolescent offspring of mothers with PPD exhibited behavioral and neurodevelopmental disorders, with male offspring being more susceptible than females. Female mice exposed to both CUMS and MS during the postnatal period had more severe adverse effects on their offspring compared to the other model groups.

Association between Temperament and Stress-related Gene Expression in Day-old Chickens.

Stress in day-old chickens from commercial hatcheries is associated with problematic behavior in adult animals. Recently, we developed a new behavioral handling test for day-old chickens and demonstrated that it assessed temperament differences between seven breeds of native Japanese and Western chickens. In this study, we used 2-day-old male chicks from five of the above breeds to investigate the relationship between temperament and mRNA levels of three stress-related genes (nuclear receptor subfamily 3 group C member 1 (NR3C1), cytochrome P450 family 11 subfamily A member 1, and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) involved in the hypothalamic-pituitary-adrenal axis. Principal component analysis of 10 behavioral traits for the handling test revealed that the Fayoumi breed and Hiroshima line of the Chabo breed, both of which exhibited boisterous temperament, clustered separately from the other breeds. Only NR3C1 expression showed a significant positive correlation with two behavioral traits (general vocalization and approaching the wall), and a negative correlation with movement. These results suggest that the complex temperament of day-old chickens is regulated, in part, by stress-related genes along the hypothalamic-pituitary-adrenal axis.

Cortisol in metabolic syndrome.

Cortisol, a stress hormone, plays a crucial role in regulating metabolic, hemodynamic, inflammatory, and behavioral processes. Its secretion is governed by the hypothalamic-pituitary-adrenal axis. However, prolonged activation of this axis and increased cortisol bioavailability in tissues can result in detrimental metabolic effects. Chronic exposure to excessive cortisol is associated with insulin resistance and visceral obesity, both significant contributors to metabolic syndrome. This review delves into the regulation of the hypothalamic-pituitary-adrenal axis, the molecular mechanisms underlying cortisol synthesis and its actions, as well as the key factors influencing cortisol bioavailability. Furthermore, it provides a summary of available clinical research data on the involvement of cortisol in metabolic syndrome, alongside a discussion on the various biomatrices used for cortisol measurement in clinical settings.

Reversible central adrenal insufficiency in survivors of COVID-19: results from a 24-month longitudinal study.

Objective: We studied the temporal course of hypothalamic-pituitary-adrenal (HPA) dysfunction in patients with coronavirus disease 2019 (COVID-19). Methods: Three hundred and two patients (median age 54 years (interquartile range (IQR) 42-64), 76% males) were recruited. The HPA axis was evaluated by morning cortisol and adrenocorticotrophic hormone (ACTH) at admission (n = 232). Adrenal insufficiency (AI) during acute illness was defined using a morning cortisol <83 nmol/L. AI at 12 months follow-up was defined using a peak cortisol <406 nmol/L in the ACTH stimulation test (APST) (n = 90). Those with AI at 12 months were further assessed by APST every 6 months for recovery of hypoadrenalism. Results: The median morning cortisol and ACTH levels during COVID-19 were 295 (IQR 133-460) nmol/L and 3.9 (0.8-6.9) pmol/L, respectively. AI was present in 33 (14%) patients; ACTH was elevated in three and low or inappropriately normal in the rest 30 patients. At 12 months, AI was seen in 13% (12/90) patients, with all cases being hypothalamic-pituitary in origin; five (42%) of them had not met the diagnostic criteria for AI during COVID-19. AI diagnosed at admission persisted at 12 months in seven patients and recovered in seven; the remaining 19 patients were lost to follow-up. The presence of AI at 12 months was independent of severity and steroid use during COVID-19. A morning cortisol <138 nmol/L during COVID-19 predicted the presence of AI at 12 months. All patients showed recovery of the HPA axis in the ensuing 12 months. Conclusion: Central AI was common during acute COVID-19 and at 12 months of follow-up. AI can be late onset, developing after recovery from COVID-19, and was transient in nature.

Neuroendocrine contribution to sex-related variations in adverse air pollution health effects.

Air pollution exposure is ranked as a leading environmental risk factor for not only cardiopulmonary diseases but also for systemic health ailments including diabetes, reproductive abnormalities, and neuropsychiatric disorders, likely mediated by central neural stress mechanisms. Current experimental evidence links many air pollution health outcomes with activation of neuroendocrine sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal (HPA) stress axes associated with resultant increases in adrenal-derived hormone levels acting as circulating mediators of multi-organ stress reactions. Epidemiological and experimental investigations also demonstrated sex-specific responses to air pollutant inhalation, which may be attributed to hormonal interactions within the stress and reproductive axes. Sex hormones (androgens and estrogens) interact with neuroendocrine functions to influence hypothalamic responses, subsequently augmenting stress-mediated metabolic and immune changes. These neurohormonal interactions may contribute to innate sex-specific responses to inhaled irritants, inducing differing individual susceptibility. The aim of this review was to: (1) examine neuroendocrine co-regulation of the HPA axis by gonadal hormones, (2) provide experimental evidence demonstrating sex-specific respiratory and systemic effects attributed to air pollutant inhalation exposure, and (3) postulate proposed mechanisms of stress and sex hormone interactions during air pollution-related stress.

Air pollution exposure responses are co-regulated by stress and sex hormonesHypothalamic and CNS stress reactions are sensitive to sex hormonesEstrogen and testosterone influence HPA axis induction and glucocorticoid dynamicsNeuroendocrine axes interactions mediate sex-specific air pollutant health effects.

Should we routinely assess hypothalamic-pituitary-adrenal axis in pediatric patients with Prader-Willi syndrome?

Background: It has been reported that central adrenal insufficiency (CAI) in pediatric patients (pts) with Prader-Willi syndrome (PWS) may be a potential cause of their sudden death. In addition, the risk of CAI may increase during treatment with recombinant human growth hormone (rhGH). Objective: To prevent both over- and undertreatment with hydrocortisone, we evaluated the prevalence of CAI in a large multicenter cohort of pediatric pts with PWS analyzing adrenal response in the low-dose ACTH test (LDAT) and/or the glucagon stimulation test (GST) and reviewing the literature. Methods: A total of 46 pts with PWS were enrolled to the study, including 34 treated with rhGH with a median dose of 0.21 mg/kg/week. LDAT was performed in 46 pts, and GST was carried out in 13 pts. Both tests were conducted in 11 pts. The tests began at 8:00 a.m. Hormones were measured by radioimmunoassays. Serum cortisol response >181.2 ng/mL (500 nmol/L) in LDAT and >199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) >90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve. Results: Three GSTs were not diagnostic (no hypoglycemia obtained). LDAT results suggested CAI in four pts, but in two out of four pts, and CAI was excluded in GST. GST results suggested CAI in only one patient, but it was excluded in LDAT. Therefore, CAI was diagnosed in 2/46 pts (4.3%), 1 treated and 1 untreated with rhGH, with the highest cortisol values of 162 and 175 ng/dL, but only in one test. However, in one of them, the cortisol delta response was >90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%). Conclusion: We present low prevalence of CAI in pediatric pts with PWS according to the latest literature. Therefore, we do not recommend to routinely screen the function of the hypothalamic-pituitary-adrenal axis (HPAA) in all pts with PWS, both treated and untreated with rhGH. According to a review of the literature, signs and symptoms or low morning ACTH levels suggestive of CAI require urgent and appropriate diagnosis of HPAA by stimulation test. Our data indicate that the diagnosis of CAI should be confirmed by at least two tests to prevent overtreatment with hydrocortisone.

Effects of acupuncture on hypothalamic-pituitary-adrenal axis: Current status and future perspectives.

The hypothalamic-pituitary-adrenal (HPA) axis is a critical component of the neuroendocrine system, playing a central role in regulating the body's stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus, hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA axis. This review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture. Please cite this article as: Zheng JY, Zhu J, Wang Y, Tian ZZ. Effects of acupuncture on hypothalamic-pituitary-adrenal axis: Current status and future perspectives. J Integr Med. 2024; 22(4): 446-459.

Adrenocortical and autonomic cross-system regulation in youth: A meta-analysis.

Childhood and adolescence are salient periods for the development of adrenocortical and autonomic arms of the stress response system (SRS), setting the stage for subsequent health and adaptive functioning. Although adrenocortical and autonomic systems theoretically function in highly coordinated ways, the strength of the relationship between these systems remains unclear. We leveraged a multivariate mixed effects meta-analytic approach to assess associations between adrenocortical, sympathetic, and parasympathetic functioning at rest and reactivity during stress-inducing tasks across 52 studies (N = 7,671; 5-20 years old). Results suggested a modest positive relation between adrenocortical and sympathetic systems as well as between adrenocortical and parasympathetic systems. Moderation analyses indicated the strength of associations varied as a function of several methodological and sociodemographic characteristics. Environmental effects on cross-system regulation were less clear, perhaps due to underrepresentation of adverse-exposed youth in the included studies. Collectively, our findings call for greater methodological attention to the dynamical, non-linear nature of cross-system functioning, as well as the role of experience in their organization across development.

The effect of total sleep deprivation on autonomic nervous system and cortisol responses to acute stressors in healthy individuals: A systematic review.

OBJECTIVE: To synthesise the literature examining the autonomic nervous system (ANS) and cortisol responses to an acute stressor following total sleep deprivation (TSD) in healthy adult subjects. METHODS: We conducted a systematic review (CRD42022293857) following the latest PRISMA statement. We searched Medline (via Ovid), Embase (via Ovid), PsycINFO (via Ovid), CINAHL complete and Scopus databases, without year restriction, using search terms related to "sleep deprivation", "stress", "autonomic nervous system" and "cortisol". Two independent team members used pre-defined inclusion/exclusion criteria to assess eligibility and extract data. We used RoB 2 to assess the risk of bias in randomised controlled trials, and ROBINS-I for non-randomised studies. RESULTS: Sixteen studies, with 581 participants (mean age = 29 ± 12 years), were eligible for inclusion in the descriptive syntheses. Half of the studies (n = 8) were conducted in the United States of America. The most commonly used study designs were randomised crossover studies (n = 7) and randomised controlled trials (n = 5). Most studies used a single night of TSD (n = 13) which was followed by a psychological (n = 6), physical (n = 5) or psychological and physical (n = 5) acute stressor event. Heart rate (n = 8), cortisol (n = 7) and blood pressure (n =6) were the most reported outcomes, while only a single study used forearm vascular conductance and forearm blood flow. Ten studies found that TSD changed, at least, one marker of ANS or cortisol response. TSD compared with a sleep control condition increased cortisol level (n=1), systolic blood pressure (n=3), diastolic blood pressure (n=2), mean arterial pressure (n=1), and electrodermal activity (n=1) after acute stress. Also, compared with a sleep control, TSD blunted cortisol (n=2), heart rate (n=1) and systolic blood pressure (n=2) responses after acute stress. However, TSD did not change ANS or cortisol responses to acute stressors in 73 % of the total reported outcomes. Furthermore, 10 RCT studies (62.5 %) were assigned as "some concerns" and two RCT studies (12.5 %) were attributed "high" risk of bias. Additionally, one non-randomised trial was classified as "moderate" and three non-randomised trials as "serious" risk of bias. CONCLUSION: The markers of ANS and cortisol responses to acute stress after TSD in healthy individuals reveal a scarcity of consistent evidence. The included studies present enough evidence that TSD induces either blunted or exaggerated ANS or cortisol responses to laboratory stresses supporting the "bidirectional multi-system reactivity hypothesis.". It appears that a comprehensive understanding of this phenomenon still lacks robust evidence, and further research is needed to clarify these relationships.

Kamishoyosan Normalizes Dendritic Spine Morphology in the Medial Prefrontal Cortex by Regulating microRNA-18 and Glucocorticoid Receptor Expressions in Postmenopausal Chronic Stress-Exposed Mice.

OBJECTIVE: Kamishoyosan (KSS), a traditional Japanese Kampo medicine, is widely used to treat neuropsychiatric symptoms in perimenopausal and postmenopausal women. We aimed to elucidate the functional mechanisms underlying KSS-mediated reduction of stress response behaviors and neuropsychological symptoms in perimenopausal and postmenopausal women. METHODS: Female mice were bilaterally ovariectomized (OVX) at the age of 12 weeks and exposed to chronic water immersion and restraint stress for three weeks. Among them, mice in the OVX+stress+KSS group were fed chow containing KSS from one week before exposure to chronic stress until the end of the experiment. Firstly, we performed a marble burying test and measured serum corticosterone levels to assess irritability and stress conditions. Next, we examined whether KSS affects microRNA-18 (miR-18) and glucocorticoid receptor (GR) protein expression, as well as the basal dendritic spine morphology of pyramidal neurons in the medial prefrontal cortex (mPFC) of postmenopausal chronic stress-exposed mice. Analyzed data were expressed as mean ± standard deviation. Tukey's post hoc test, followed by analysis of variance (ANOVA), was used for among-group comparisons. RESULTS: KSS administration normalized chronic stress-induced unstable emotion-like behavior and upregulated plasma corticosterone levels. Furthermore, KSS ameliorated GR protein expression by downregulating miR-18 expression in the mPFC and recovered the immature morphological changes in spine formation of pyramidal neurons in the mPFC of OVX mice following chronic stress exposure. CONCLUSIONS: KSS administration in postmenopausal chronic stress-exposed mice exerted anti-stress effects and improved the basal dendritic spine morphology of pyramidal neurons by regulating miR-18 and glucocorticoid receptor expression in the mPFC.

Child Maltreatment and Psychopathology: A Brief Review on the Potential Role of the Hypothalamic-pituitary-adrenal Axis.

Child maltreatment is a widespread global issue involving any form of harm or neglect by a parent or caregiver, leading to various forms of physical or emotional damage, with approximately 150 million affected children globally. This study discusses the potential mechanism of the hypothalamic-pituitary-adrenal axis dysfunction and cortisol hormone changes in linking child maltreatment to mental health disorders. It also discusses supportive strategies to prevent mental diseases and counteract the biological embedding of these conditions, emphasizing the need for comprehensive interventions to address the long-term impact of child maltreatment on mental health. Articles were selected using established methods previously described. Key information was obtained from scientific articles published during the past 20 years, including original studies, systematic reviews, and meta-analyses. Articles search was performed using top academic search engines. While research on hypothalamic-pituitary-adrenal axis response to stress in maltreated children is ongoing and far from conclusive, its impact and implications for physiological functioning and the predisposition to psychopathology are significant. Childhood maltreatment increases the risk of psychiatric illnesses, severity of diseases, and poor treatment responses. Childhood maltreatment manifests as disruptions to hypothalamic-pituitary-adrenal axis functioning, with the extent varying based on factors, such as the age of onset, parental responsiveness, and the type and characteristics of maltreatment. The complex interplay of these factors contributes to the diversity of hypothalamic-pituitary-adrenal axis responses to stress in maltreated children, creating a spectrum of physiological functioning and vulnerability to psychopathology.