Search Results (490)

Many individuals suffer from sleep disorders associated with chronic pain, neuroendocrine diseases, and primary sleep disorders. Although cervical manual therapy (CMT) is frequently presumed to enhance sleep quality in clinical settings, evidence regarding its effects on sleep remains inconclusive. We aimed to evaluate the therapeutic effect of CMT and clinical patterns, providing novel insights into its applicability for sleep disorders and further mechanism studies. Methods: A comprehensive literature survey was conducted by using 6 databases through February 2025, to identify randomized controlled trials (RCTs) assessing the effect of CMT on sleep quality as clinical outcome, regardless of primary diseases. Results: Among 1220 initial studies, a total of 10 RCTs involving 552 participants were included. All included RCTs assessed sleep quality using patient-reported outcome measures, while only one study utilized objective assessment via polysomnography. Among them, seven RCTs (70.0%) reported significant improvements in sleep quality that were not dependent on alleviating the primary diseases, with notable enhancements in subjective sleep depth and efficiency rather than sleep duration or latency. Sleep benefits were pronounced in primary sleep disorders, such as obstructive sleep apnea and bruxism, and in sleep disturbances secondary to other conditions, with limited effects in fibromyalgia (FM). Conclusions: With the dysregulated hypothalamic–pituitary–adrenal axis and aberrant serotonergic activity in FM, in this review, we formed a hypothesis and explored the potential effects of CMT on sleep-related serotonergic activity and HPA axis regulation. This scoping review underscores the need for further research to clarify the neuroendocrinological mechanisms underlying CMT’s role in sleep modulation and its potential applications in sleep-related disorders. Full article

Personalized psychiatry represents an innovative therapeutic approach that integrates biological, genetic, and clinical data to optimize the treatment of mental disorders. Laboratory diagnostics play a fundamental role in this process by providing precise biomarkers that characterize pathophysiological mechanisms such as neuroinflammatory processes, oxidative stress, dysfunction of the Hypothalamic–Pituitary–Adrenal (HPA) axis, as well as disturbances in neuroplasticity and neurodegeneration. This article discusses the use of advanced analytical techniques, such as immunoenzymatic assays for pro-inflammatory cytokines (Interleukin-1β- IL-1β; Interleukin-6-IL-6; Interleukin-18-IL-18; and Tumor Necrosis Factor- α - TNF-α). It also emphasizes the role of pharmacogenomic diagnostics in the individualization of psychotropic therapy. Interdisciplinary collaboration between laboratory diagnosticians and clinicians supports the potential for multidimensional analysis of biomarker data in a clinical context, which supports precise patient profiling and monitoring of treatment responses. Despite progress, there are limitations, such as the lack of standardization in measurement methods, insufficient biomarker validation, and limited availability of tests in clinical practice. Development prospects include the integration of multi-marker panels, the use of point-of-care diagnostics, and the implementation of artificial intelligence tools for the analysis of multidimensional data. As a result, laboratory diagnostics are becoming an integral element of personalized psychiatry, enabling a better understanding of the neurobiology of mental disorders and the implementation of more effective therapeutic strategies. Full article

The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article

Endocrine axes are pathways of interactions involved in various aspects of the organism’s functioning, also implicated in deviations from physiological states leading to pathological conditions. The hypothalamic–pituitary–adrenal (HPA) axis releases corticosteroid hormones promoting adaptation to environmental stimuli (acute stress) or inducing altered conditions due to long-term noxious solicitations (chronic stress). The HP–gonadal (HPG) axis regulates reproductive activities by releasing gonadal steroids. These axes have been shown to engage in reciprocal inhibition under certain conditions, particularly when they rise beyond normal ultradian and circadian fluctuations. Based on the literature data, we reconstructed a neuroendocrine network responsible for this type of interaction. Thereafter, we developed a model of the HPA-HPG inhibition based on a series of nonlinear interactions represented by a system of differential equations in the Matlab environment. The quantitative analysis of the system’s behavior revealed the occurrence of bifurcations leading to bistable behavior, allowing us to detect bifurcation parameters. Bifurcation arises as the system’s components increase hypersensitivity and sustained activity in response to activating inputs. This involves transition from a single low-activity attractor to two distinct attractors, with a new high-activity state representing a breakdown of homeostasis. These results provide insights into the potential involvement of the HPA-HPG interaction in neuroendocrine disorders, and the identification of therapeutic targets from bifurcation parameters. Full article

Depression is a prevalent and disabling psychiatric disorder, characterized by persistent disturbances in mood, cognition, and physiological processes, which collectively lead to substantial impairments in daily functioning and quality of life. This review provides a comprehensive overview of the biological mechanisms implicated in the pathophysiology of depression, including neurotransmitter dysregulation, oxidative stress, inflammatory processes, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, mitochondrial impairment, and alterations in the gut-brain axis. Furthermore, it explores the role of diet in both the prevention and management of depression, with particular emphasis on Mediterranean, anti-inflammatory, and ketogenic dietary patterns, while contrasting these with the detrimental impact of a Western dietary pattern. Specific nutrients-such as n-3 polyunsaturated fatty acids (PUFAs), B-complex vitamins, vitamins D and E, zinc, selenium, and polyphenols-are highlighted for their potential roles in modulating neurotransmission, attenuating inflammation, and supporting gut microbiota homeostasis. Despite growing scientific interest in nutrition-based interventions, current evidence on the comparative efficacy of different dietary approaches remains limited. Future research is warranted to elucidate the therapeutic potential of dietary strategies as adjuncts to conventional treatments for depression and to facilitate the development of evidence-based nutritional recommendations for clinical practice. Full article

Preterm birth remains a significant global health challenge and is strongly associated with heightened risks of long-term neurodevelopmental impairments, including cognitive delays, behavioural disorders, and emotional dysregulation. In recent years, accumulating evidence has underscored the critical role of the gut microbiota in early brain development through the gut–brain axis. In preterm infants, microbial colonisation is frequently delayed or disrupted due to caesarean delivery, perinatal antibiotic exposure, formula feeding, and prolonged stays in neonatal intensive care units (NICUs), all of which contribute to gut dysbiosis during critical periods of neurodevelopment. This review synthesises current knowledge on the sources, temporal patterns, and determinants of gut microbiota colonisation in preterm infants. This review focuses on the gut bacteriome and uses faecal-sample bacteriome sequencing as its primary method of characterisation. We detail five mechanistic pathways that link microbial disturbances to adverse neurodevelopmental outcomes: immune activation and white matter injury, short-chain fatty acids (SCFAs)-mediated neuroprotection, tryptophan–serotonin metabolic signalling, hypothalamic–pituitary–adrenal (HPA) axis modulation, and the integrity of intestinal and blood–brain barriers (BBB). We also critically examine emerging microbiota-targeted interventions—including probiotics, prebiotics, human milk oligosaccharides (HMOs), antibiotic stewardship strategies, skin-to-skin contact (SSC), and faecal microbiota transplantation (FMT)—focusing on their mechanisms of action, translational potential, and associated ethical concerns. Finally, we identify key research gaps, including the scarcity of longitudinal studies, limited functional modelling, and the absence of standardised protocols across clinical settings. A comprehensive understanding of microbial–neurodevelopmental interactions may provide a foundation for the development of targeted, timing-sensitive, and ethically sound interventions aimed at improving neurodevelopmental outcomes in this vulnerable population. Full article

Background: Adverse childhood experiences (ACEs) can lead to hypothalamic–pituitary–adrenal axis dysregulation, negatively impacting child growth and development. Methods: The Hair Biomarkers Study (HBS-I) evaluated healthy preschool children using parent-reported surveys, anthropometrics, and painlessly obtained scalp hair to measure hair cortisol (HCC; ng/mg) and oxytocin concentrations (HOC; ng/mg) via ELISA; log-transformed data were used in analyses. Height, weight, and BMI percentiles were based on CDC growth curves. Linear regressions examined associations of child and maternal hair biomarkers with percentiles, adjusting for sociodemographic factors. Results: The median age was 39.1 months (IQR 23.5–53.0, N = 1189). Higher child Ln-HCC was associated with an increased BMI percentile (0.027; 95%Cl: 0.013, 0.040), while higher child Ln-HOC was associated with a decreased BMI (−0.016; 95%Cl: −0.028, −0.005). Similar significant associations were observed between maternal biomarkers and child growth. In models mutually adjusted for mother and child hair biomarkers, maternal Ln-HCC was associated with an increased BMI percentile (0.036; 95%Cl: 0.003, 0.069), while maternal Ln-HOC was associated with a decreased BMI percentile (−0.034; 95%Cl: −0.052, −0.016). Maternal ACEs of 2–3 vs. 0–1 were associated with increased child weight (0.057; 95%Cl: 0.003, 0.112) and BMI percentiles (0.076; 95%Cl: 0.017, 0.135). Conclusions: We show that higher maternal and child HCC was associated with increased child BMI percentiles, while higher HOC was linked with decreased BMI percentiles. Hair biomarkers may reflect the effects of nurturing vs. adverse experiences during critical windows of growth and development in early childhood. Full article

Cortisol follows a 24 h circadian rhythm that plays a pivotal role in maintaining the optimal function of various physiological systems in alignment with behavioural cycles. Its synthesis and secretion are regulated by the hypothalamic–pituitary–adrenal (HPA) axis. The 24 h fluctuations of cortisol may result from physiological changes influencing its regulation, or conversely, hormone-mediating physiological changes within the body. This review mainly aims to synthesize current evidence on methods for detecting cortisol. In addition, it focuses on evaluating cortisol’s potential as a biomarker for circadian disruption and related health impacts. A literature search was conducted across databases, including Google Scholar, PubMed, and Scopus, using search terms such as “circadian rhythm OR circadian clock OR circadian disruption OR circadian dysregulation” and “cortisol OR hydrocort* OR corticoid OR corticosteroid”. A total of 47 articles were included on methods of cortisol detection, and 41 articles were reviewed for their health implications. Cortisol measured via saliva, blood serum, urine, interstitial fluid (ISF), and sweat has been reported as suitable for 24 h monitoring, reflecting circadian regulation. In contrast, hair cortisol is suitable for identifying chronic changes and prolonged elevations in cortisol levels. This review highlights the stability, suitability, and challenges of each detection method, including reported cortisol levels across studies. Additionally, it provides a comprehensive overview of health implications associated with changes in cortisol, offering insights into its potential as a marker for circadian disruption and related health outcomes. Full article

Background: Takotsubo Syndrome (TTS), or stress-induced cardiomyopathy, is an acute and typically reversible cardiac condition that mimics acute coronary syndrome without obstructive coronary artery disease. Predominantly affecting postmenopausal women, TTS has been increasingly recognized as a psychobiological disorder involving neuroendocrine dysregulation, autonomic imbalance, psychosocial stress, and gendered patterns of emotional regulation. This review aimed to synthesize multidisciplinary evidence to propose an integrative, gender-informed model of TTS. Methods: A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science (2000–2025) to identify clinical, neurobiological, psychosocial, and psychoanalytic studies addressing sex/gender differences, psychiatric comorbidities, and emotional regulation in TTS. Results: Evidence indicates that catecholamine surge, hypothalamic–pituitary–adrenal axis dysregulation, estrogen deficiency, and autonomic imbalance provide a biological substrate for stress-induced myocardial stunning. Psychosocial factors, such as caregiving burden, chronic stress, and alexithymia, further decrease resilience. Gendered coping scripts and unconscious symbolic processes may amplify vulnerability and influence clinical presentation. The integrative model combines biological, psychological, and social mechanisms, highlighting the predominance of emotional triggers in women and worse in-hospital outcomes in men. Conclusions: TTS should be approached as both a cardiac and affective disorder. Gender-sensitive, multidisciplinary management, including psychiatric screening, psychocardiology interventions, and psychoanalytically informed care, may improve prevention, diagnosis, and patient outcomes. Full article

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are among the leading causes of disability worldwide and are frequently associated with treatment resistance, functional impairment, and high comorbidity with metabolic dysfunction. Increasing evidence implicates insulin resistance (IR) as a key pathophysiological factor linking metabolic and psychiatric illness. IR is associated with chronic low-grade inflammation, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, impaired neuroplasticity, mitochondrial dysfunction, and altered reward processing mechanisms that may contribute to core depressive features such as anhedonia, cognitive slowing, and emotional dysregulation. These processes are further exacerbated by the metabolic side effects of many psychotropic medications, creating a self-perpetuating cycle that worsens both psychiatric and physical health outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for type 2 diabetes and obesity, have emerged as promising candidates to address this metabolic–psychiatric interface. Beyond improving glycemic control and promoting weight loss, GLP-1 RAs exert central actions relevant to mood disorders, including modulation of dopaminergic reward pathways, enhancement of hippocampal neurogenesis, attenuation of neuroinflammation, and regulation of appetite and energy balance. Preclinical studies demonstrate that GLP-1 RAs reduce microglial activation, promote hippocampal neurogenesis, and normalize stress-induced behavioral changes. Early clinical trials in patients with metabolic disorders suggest improvements in depressive symptoms, quality of life, and cognitive function, with some effects independent of weight loss or glycemic outcomes. Observational evidence also indicates reduced antidepressant use and psychological distress in diabetic and obese populations receiving GLP-1 RAs. While these findings are promising, large randomized controlled trials in primary psychiatric populations are lacking. Key challenges include clarifying dose–response relationships, disentangling central from peripheral effects, and addressing safety and adherence concerns in individuals with comorbid psychiatric conditions. Future research should focus on biomarker-informed stratification, comparative trials with standard treatments, and integration of GLP-1 RAs into multimodal care frameworks. Overall, GLP-1 RAs represent a biologically plausible and clinically relevant approach to bridging metabolic and psychiatric care, with the potential to improve outcomes in patients with mood disorders who carry a high metabolic burden. Full article

Male infertility is a growing global concern with increasing prevalence in both developing and developed nations. While many associations between environmental factors and male infertility have been explored, the relationship between sleep deprivation and male infertility remains underexplored. This narrative review examines the reported effects of sleep deprivation on the Hypothalamic––Gonadal (HPG) axis, Hypothalamic–Pituitary–Adrenal (HPA) axis, oxidative stress, and testicular function, and their consequential effects on male infertility. Disruption of the HPG axis results in altered follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, leading to fluctuation in testosterone levels, negatively affecting spermatogenesis and other critical reproductive processes. Activation of the HPA axis, often due to stress, elevates cortisol levels, which, in turn, suppresses gonadotropin-releasing hormone (GnRH), impairing reproductive function. Reactive oxidative species (ROS) accumulate in periods of oxidative stress and have been shown to damage sperm and reduce their quality. The blood–testis barrier (BTB) is disrupted in states of sleep deprivation, leading to decreased sperm quality. A literature review was conducted using PubMed and Google Scholar to assess peer-reviewed studies from 1990 to 2024, revealing a complex interplay between sleep deprivation and male reproductive dysfunction. While existing studies support a link between sleep disturbances and hormonal dysregulation, further research is needed to establish causal relationships and identify potential therapeutic interventions. Addressing sleep deprivation may represent a modifiable factor in improving male fertility outcomes. Full article

Irritable Bowel Syndrome (IBS) and Metabolic dysfunction-associated fatty liver disease (MAFLD) have traditionally been viewed as disorders of distinct organ systems. IBS is a gut–brain axis disorder characterized by abdominal pain, altered bowel habits, and psychological comorbidities. MAFLD, recently redefined to emphasize its metabolic underpinnings, is the hepatic manifestation of systemic metabolic dysfunction. Growing evidence suggests that these conditions share overlapping pathophysiological mechanisms linked through disruption of the gut–liver–brain axis (GLBA), including psychological stress, gut dysbiosis, impaired intestinal permeability, systemic inflammation, and altered neuroendocrine signaling. Neuroimaging studies further reveal functional alterations in brain regions responsible for interoception, emotional regulation, and stress responsiveness in both disorders. This narrative review explores how psychological distress influences the onset and progression of IBS and MAFLD via GLBA dysfunction and stress-induced epigenetic reprogramming. A targeted literature search of major biomedical databases, supplemented by manual screening, identified relevant observational, clinical, neuroimaging, and molecular studies. Findings indicate that chronic psychological distress activates the hypothalamic–pituitary–adrenal (HPA) axis, elevates cortisol, disrupts gut microbiota, and reduces vagal tone; amplifying intestinal permeability and microbial translocation. These changes promote hepatic inflammation and gastrointestinal symptoms. Stress-related epigenetic modifications further impair GLBA communication, while psychological and lifestyle interventions may reverse some of these molecular imprints. Recognizing the shared neuromodulation and epigenetic mechanisms that link IBS and MAFLD opens promising avenues for integrated therapeutic strategies targeting the GLBA to improve outcomes across both conditions. Full article

Cushing’s disease (CD) is a rare neuroendocrine disorder caused by ACTH-secreting pituitary adenomas, presenting significant diagnostic and therapeutic challenges. Given the evolutionary conservation of the hypothalamic–pituitary–adrenal axis, this review explores the translational value of spontaneous CD forms in dogs, horses, cats, small mammals, and rats, as well as of experimental models in mice, rats, and zebrafish. Dogs are the most studied, showing strong molecular and clinical similarities with human CD, making them valuable for preclinical drug and diagnostic research. While equine and feline CD are less characterized, they may provide insights into dopaminergic therapies and glucocorticoid resistance. Nevertheless, practical and ethical challenges limit the experimental use of companion animals. In preclinical research, mouse models are widely used to study hypercortisolism and test therapeutic agents via transgenic and xenograft strategies. Conversely, few studies are available on a zebrafish transgenic model for CD, displaying pituitary corticotroph expansion and partial resistance to glucocorticoid-negative feedback at the larval stage, while adults exhibit hypercortisolism resembling the human phenotype. Future transplantable systems in zebrafish may overcome several limitations observed in mice, supporting CD research. Collectively, these animal models, each offering unique advantages and limitations, provide a diverse toolkit for advancing CD research and improving human clinical outcomes. Full article

Gulf War illness (GWI) is a multi-symptom disorder affecting veterans of the Persian Gulf operations. Persistent neuroendocrine dysregulation contributes to impairing cognitive capacity and generates anxiety-like behavior. Effective treatments for this illness are challenging due to compromised metabolism, increased oxidative stress and neuroinflammation, perpetuated by chronic stress and hypothalamic–pituitary–adrenal (HPA) axis dysfunction. This neuroinflammation can be alleviated with synthetic antagonistic analogs of the growth hormone-releasing hormone (GHRH) through modulation of the HPA axis. We evaluated the efficacy of the GHRH antagonist analog, MIA-690, against cognitive impairment and anxiety-like behavior in GWI. Mice exposed to an experimental GWI model involving corticosterone (CORT) and diisopropylfluorophosphate (DFP), followed by CORT and lipopolysaccharide (LPS), received a daily subcutaneous dose of 10 μg of MIA-690 for 10 days. Assessments of spatial memory, recognition capacity, somatic health, anxiety and innate survival were carried out, combining the Morris water maze (MWM), novel object recognition (NORT), grip strength (GST), and open field (OFT) tests. Learning efficiency was selectively enhanced in females using the MWM. There were no significant differences in the recall capacity and performance on the OFT, NOR, and GST tasks. Our findings suggest that the MIA-690 dosage is sufficient to improve learning deficits in experimental GWI exposures. Full article

The corticotropin-releasing factor (CRF) and its type 1 receptor (CRF₁R) play a key role in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis. Dysregulation of the HPA axis is associated with congenital adrenal hyperplasia (CAH) and depression. Non-peptide CRF₁R-selective antagonists displayed antidepressant effects on animal models and are used for the management of CAH. To develop novel non-peptide CRF₁R antagonists, we have previously designed and synthesized a series of substituted pyrimidines. Among these analogs, molecule 43 (M43) binds to CRF₁R with the highest affinity. Based on this finding, we selected M43 for further pharmacological characterization in the present study. The results suggest that M43 is a potent CRF₁R antagonist, blocking the ability of the CRF-related agonist, Tyr⁰-sauvagine, to stimulate (1) cAMP accumulation in HEK 293 cells expressing CRF₁R and (2) the proliferation rate of RAW 264.7 macrophages. Computational studies suggest that the antagonist properties of M43 are mostly attributed to its ability to interact with residues in the allosteric pocket of CRF₁R, comprised of the third, fifth, and sixth transmembrane domain residues, which block activation-associated structural rearrangements of the receptor. Our data will be used to design novel non-peptide CRF₁R antagonists for clinical use. Full article