Search Results (1,882)

Professional soccer imposes substantial physiological demands eliciting complex neuroendocrine responses. This review synthesizes evidence on hormonal adaptations in professional soccer players, with emphasis on ethnic and national differences and underlying pathophysiological mechanisms. We analyzed 21 key studies investigating testosterone, cortisol, the testosterone-to-cortisol (T:C) ratio, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) responses to training and competition. Acute cortisol elevations that may persist for up to 72 h post-match in some professional populations and T:C ratio reductions following congested fixture periods are reported across available studies, while somatotropic responses vary considerably across studies. Preliminary evidence suggests that ethnic and geographic background may influence circulating testosterone and urinary steroid excretion profiles, with UGT2B17 genetic polymorphisms identified as one contributing factor; however, the evidence base is limited and requires replication. Approximately 7.4% of elite junior cohorts—though not necessarily professional adult populations—develop non-functional overreaching (NFOR), characterized by blunted GH and ACTH responses. Pathophysiological mechanisms involve hypothalamic–pituitary––adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) axis dysregulation producing anabolic–catabolic imbalance. Individualized, longitudinal T:C monitoring and post-match load moderation may be warranted; future research should establish ethnicity-specific normative values and investigate links between hormonal dysregulation and injury risk. Full article

Stress alters hemodynamic regulation through intricate brain–body pathways, translating psychological phenomena into systemic cardiovascular changes. This review explores these complex neurobiological mechanisms, focusing on how the autonomic nervous system and hypothalamic–pituitary–adrenal axis orchestrate pathological fluctuations in heart rate, vascular resistance, and blood pressure. The neurophysiological data link limbic system hyperactivation to endothelial dysfunction and altered cerebral blood flow. Furthermore, we investigate the bidirectional nature of this relationship wherein stress-induced hemodynamic instability can exacerbate psychiatric conditions. Bridging affective neuroscience with cardiovascular physiology, this integrative framework underscores the critical need for multidisciplinary clinical approaches in managing stress-related psychosomatic and cardiovascular pathologies. Full article

Carbon monoxide (CO) is a gasotransmitter generated by heme oxygenase (HO) isoforms during heme catabolism. The inducible HO-1 produces CO under conditions of redox imbalance, such as oxidative stress and inflammation. On the other hand, HO-2 constitutively generates CO, primarily during the physiological turnover of heme. Extensive evidence indicates that CO exerts autocrine effects by targeting hemoproteins, including soluble guanylyl cyclase, cyclooxygenase, and cytochromes. Furthermore, CO regulates many biological processes within the brain, including mitochondrial biogenesis, potassium channel activity, mitogen-activated protein kinase and phosphatidylinositol-3-kinase/Akt signaling. It also controls the activity of transcription factors, such as hypoxia-inducible factor-1 and peroxisome proliferator-activated receptor-γ. Through these mechanisms, CO modulates inflammatory gene expression, promotes anti-apoptotic signaling, and contributes to local stress responses. Conversely, CO produced in the hypothalamus inhibits the stress-induced release of corticotropin-releasing hormone and arginine vasopressin under pro-inflammatory conditions, resulting in reduced adrenocorticotropin hormone release and cortisol secretion from the anterior pituitary and adrenal cortex, respectively. Moreover, hypothalamic CO acts in a paracrine manner to modulate glucocorticoid release during psychological stress, including restraint or water deprivation. Together, these findings support the view that endogenous CO is a key modulator of the stress axis, exerting pleiotropic effects that integrate neuroendocrine, immune, and metabolic responses. Full article

Background: Polycystic ovarian syndrome (PCOS) and the non-classic form of congenital adrenal hyperplasia (NC-CAH) are hyperandrogenic conditions with overlapping clinical symptoms but different genetic backgrounds. The possible interrelationships between the two conditions remain unclear; thus, the present study aims to investigate the prevalence of CYP21A2 exon 7 genetic variants in patients with PCOS and to explore the possible associations of the polymorphisms with adrenocortical hormonal production. Methods: The CYP21A2 exon 7 region was genotyped in 80 unrelated female patients with PCOS and 12 women with NC-CAH. The associations between genetic variants, clinical characteristics, and adrenocortical hormones were investigated. Results: The pathogenic CYP21A2 NC-CAH variant c.844G>T; p.(Val282Leu) was found in 66.7% (8/12) of patients with NC-CAH but in none of the individuals with PCOS. The benign rs1554305325, rs6465, rs6472, and rs6477 genetic polymorphisms were not related to clinical hyperandrogenism. The rs6472 polymorphic alleles were associated with increased adrenocorticotropic hormone (ACTH) (5.5 vs. 3.4 pmol/L, p = 0.022) and cortisol (460.5 vs. 366.5 nmol/L, p = 0.016) levels. The rs6465 variant alleles were significantly associated with lower pregnenolone (1.43 vs. 3.1 ng/mL, p = 0.031) and ACTH (2.5 vs. 4.5 pmol/L, p = 0.030) levels in the unadjusted model but not after adjustment for potential confounders (p > 0.05). Conclusions: The p.(Val282Leu) variant is very common among Bulgarian patients with NC-CAH but it has not been found in our cohort of women with PCOS. The CYP21A2 exon 7 polymorphisms might be associated with cortisol levels in the patients with PCOS. Further larger studies are needed to confirm or reject the current findings in different ethnic groups. Full article

Background and Clinical Significance: Thyroid cancer is increasing, particularly the differentiated type, with decreasing incidence of the anaplastic type. Anaplastic thyroid carcinoma (ATC) is a rare, aggressive, and often lethal form. It frequently presents with metastatic disease, regional and systemic, with common distant metastasis to the lung, bone, brain, and adrenal, and rarely to other places; Case presentation: A 74-year-old Arab male presented with symptomatic anemia and melena and was admitted for investigation of the cause. The patient was found to have a large retrosternal goiter and gastric tumor. CT scan showed a pedunculated, nonobstructive mass, suggestive of a GIST or leiomyoma. The neck mass presented with compressive symptoms. He underwent a combined neck and abdominal surgical resection based on a multidisciplinary team decision, as prior biopsies were not conclusive. The final pathology report identified similar tumors in the two specimens and suggested an anaplastic thyroid carcinoma as the primary tumor with metastasis to the stomach. Furthermore, the workup, including a PET scan 2 weeks post-surgery, revealed widespread metastases in the bone, lung, and liver, and the treatment was palliative. He was followed up in the outpatient clinic for 4 and a half months post-operatively. The patient developed sepsis and cardiopulmonary arrest and died; Conclusions: ATC can metastasize to many places in the body, including the stomach (as shown in our case), which can cause significant upper gastrointestinal bleeding and anemia. Metastatic ATC carries a poor prognosis; thus, physicians need to keep a high index of suspicion in approaching similar cases. A multidisciplinary approach for the management is of utmost importance for appropriate treatment. This disease’s pathology, behavior, and targeted new treatment modalities must be explored further. Full article

Background/Objectives: Insomnia is one of the most prevalent and persistent symptoms among patients with breast cancer, yet it remains under-recognized and undertreated in routine clinical practice. Beyond its impact on sleep quality, insomnia is increasingly understood as a multidimensional condition involving neurobiological, psychological, and behavioral mechanisms, closely intertwined with cancer-related stress and psychiatric comorbidities. This narrative review aims to provide a comprehensive and integrative overview of insomnia in breast cancer, focusing on its epidemiology, pathophysiological underpinnings, neuropsychiatric correlates, and clinical implications, while highlighting gaps in current research and management. Methods: A narrative review of the literature was conducted, including studies published in major medical databases (PubMed, Scopus, and Web of Science) up to 2025. Relevant articles addressing insomnia, sleep disturbances, psychiatric symptoms, and neurobiological mechanisms in breast cancer populations were selected and synthesized. Results: Insomnia affects a substantial proportion of breast cancer patients across the disease trajectory, from diagnosis to survivorship. Its etiology is multifactorial, involving dysregulation of the hypothalamic–pituitary–adrenal axis, inflammatory processes, and circadian rhythm, as well as treatment-related factors such as chemotherapy, endocrine therapy, and menopausal symptoms. Insomnia frequently co-occurs with depression, anxiety, fatigue, and pain, forming symptom clusters that significantly impair quality of life and may influence clinical outcomes. Emerging evidence supports a bidirectional relationship between insomnia and psychiatric vulnerability, suggesting a shared neurobiological substrate within the brain–body stress axis. Conclusions: Insomnia in breast cancer should be conceptualized as a neuropsychiatric condition embedded within a broader stress-related symptom network rather than as an isolated sleep disturbance. Improved screening, interdisciplinary management, and the integration of evidence-based interventions such as cognitive behavioral therapy for insomnia are essential. Research should focus on personalized and mechanistically informed approaches to better address this highly prevalent yet insufficiently managed condition. Full article

Background: This randomized parallel-group clinical study evaluated salivary cortisol as a biomarker of perioperative stress response during surgical extraction of impacted mandibular third molars performed under local anesthesia administration of ropivacaine and dexamethasone. Methods: The trial was registered in the ISRCTN registry (ISRCTN87752106). Ninety patients undergoing impacted mandibular third molar surgery were randomly assigned (1:1:1; n = 30/group) to receive inferior alveolar nerve block with 0.5% ropivacaine plus dexamethasone (R+D group), 0.5% ropivacaine (R group), or 0.5% bupivacaine (B group). Salivary cortisol as the primary outcome was measured at 15 min before anesthesia, and 15 min and 24 h postoperatively. Preoperative psychological stress was assessed using the Revised Norman Corah Dental Anxiety Scale. Results: No significant differences were observed between groups in preoperative anxiety (p = 0.890) or baseline salivary cortisol levels (p = 0.984). Significant intergroup differences in cortisol levels were observed at 15 min (p = 0.002) and 24 h postoperatively (p = 0.001). Cortisol levels at 15 min postoperatively were significantly lower in the R+D group compared to the R (p = 0.001) and B groups (p = 0.004) and after 24 h (R+D vs. R: p = 0.005; R+D vs. B: p < 0.001). Conclusions: The ropivacaine–dexamethasone administration significantly reduced perioperative salivary cortisol levels compared to ropivacaine alone or bupivacaine alone during impacted mandibular third molar surgery. This modulation of the neuroendocrine response likely results from dexamethasone-induced suppression of hypothalamic–pituitary–adrenal axis and the improved analgesic effects of this combination. The observed results may contribute to improved physiological stability, postoperative recovery and the clinical benefit of this anesthetic approach in oral surgery. Full article

Major depressive disorder (MDD) is a complex and heterogeneous psychiatric disorder with a high prevalence. Neuroinflammation may define biologically distinct patient subgroups with different mechanisms, clinical phenotypes, and treatment responses. This narrative review integrates current evidence around three linked questions: how neuroinflammatory processes contribute to depression, how biomarkers can identify clinically relevant inflammatory phenotypes, and how these findings can inform anti-inflammatory treatment strategies. The major mechanisms discussed include microglial activation and neuroimmune signaling, hypothalamic–pituitary–adrenal axis dysregulation and glucocorticoid receptor resistance, kynurenine pathway alterations, and cytokine-driven impairment of neurogenesis and synaptic plasticity. These pathways interact with stress responses, neurotransmitter systems, and neuronal function, while their expression may vary according to sex, age, hormonal status, disease stage, and treatment exposure. These interconnected pathways may contribute to depressive symptoms by disrupting neurotransmitter systems and impairing neural plasticity. In addition, this review discusses several candidate biomarkers, including C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF) and transforming growth factor-β1 (TGF-β), which may support patient stratification, treatment prediction, and assessment of target engagement. Clinical trials of anti-inflammatory agents have shown inconsistent and generally modest effects in unselected MDD populations. By integrating mechanistic evidence with biomarker-guided therapeutic implications, this review aims to clarify how neuroinflammatory research may inform more precise and individualized treatment strategies for depression. Full article

Military burn pits used during post-9/11 U.S. military deployments functioned as uncontrolled combustion systems and were widely utilized to dispose of large volumes of outdoor waste by burning. Burn pits involved heterogeneous waste materials burned under variable temperature and oxygen conditions. These combustion environments generated complex, toxic, multipollutant airborne emission mixtures that included particulate matter (PM_2.5), polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). This narrative review synthesizes epidemiologic, experimental, and mechanistic evidence linking burn pit emissions to disruption of the lung–brain axis and adverse neurological outcomes. We specifically aim to address a critical gap in understanding how combustion-derived toxicants impact brain health and are associated with unfavorable neuropsychiatric outcomes, including increased risk of post-traumatic stress disorder (PTSD) and depression. Combustion-related exposures promote pulmonary inflammation and system-wide immune signaling that propagate to the central nervous system, contributing to neuroinflammation and dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. These interconnected mechanisms are associated with toxic encephalopathy and related cognitive and mood disturbances, underscoring the need to integrate fire science with military and environmental health services research to better define the systemic and neurological consequences of acute and chronic fire-derived inhalation exposures. Full article

Psychiatric disorders represent a leading cause of disability worldwide and are characterized by substantial biological and therapeutic heterogeneity. Despite significant research efforts, peripheral biomarkers capable of guiding diagnosis, patient stratification, and personalized treatment selection are still lacking. Circulating cell-free DNA (cfDNA) has recently emerged as a promising candidate biomarker, as it may integrate signals of cellular damage, apoptotic activity, and immune activation across multiple tissues. Beyond its role as a marker, cfDNA may also actively contribute to disease processes by functioning as a damage-associated molecular pattern (DAMP), thereby perpetuating inflammatory signaling. The mitochondrial component of cfDNA (cf-mtDNA), which also possesses strong immunostimulatory properties, represents a particularly sensitive indicator of mitochondrial vulnerability to stress. In this context, the present review aims to synthesize the most recent evidence on cfDNA and cf-mtDNA in major psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). Specifically, we examine their association with psychological stress exposure and childhood trauma, as well as their involvement in inflammation-related pathophysiological mechanisms such as mitochondrial dysfunction, oxidative stress, and hypothalamic–pituitary–adrenal (HPA) axis dysregulation. Available evidence suggests that alterations in cfDNA may be present in subgroups of patients with MDD, BD, and SCZ. However, findings remain heterogeneous and sometimes contradictory, partly due to methodological limitations, including the lack of standardized analytical protocols and insufficient control for potential confounders. Nevertheless, cfDNA holds promise as a tool for inflammation-based patient stratification and for informing personalized therapeutic strategies. Future research directions include the integration of cfDNA within multi-omics frameworks, the analysis of cfDNA methylation profiles to infer tissue of origin, and the exploration of pharmacological strategies aimed at modulating cfDNA as a potential therapeutic target. Full article

Background/Objectives: Vitamin D is a nutrient-related secosteroid system with endocrine, paracrine, immunological, and neurodevelopmental actions relevant to nutritional psychiatry. Psychiatric research has often treated vitamin D either as a cross-sectional correlate of depression or as a non-specific supplement expected to act across heterogeneous diagnostic categories. This narrative review aimed to develop a more discriminating framework in which vitamin D is considered a lifespan neuroimmune and immunometabolic signal whose psychiatric relevance depends on developmental timing, biological context, and phenotype. Methods: Evidence was integrated from developmental epidemiology, neonatal dried-blood-spot studies, randomized trials, meta-analyses, Mendelian randomization studies, clinical guidelines, and mechanistic neuroscience. The review focuses on prenatal and neonatal 25-hydroxyvitamin D, vitamin D-binding protein, free and bioavailable vitamin D, vitamin D receptor signaling, immune and microglial pathways, neurotransmitter systems, neurotrophic signaling, mitochondrial function, oxidative stress, hypothalamic–pituitary–adrenal-axis regulation, and the gut–microbiota–immune–brain axis. Results: The available evidence does not support vitamin D as a universal treatment for psychiatric disorders. Instead, vitamin D deficiency and altered vitamin D biology appear most relevant in biologically and clinically defined risk states, including neurodevelopmental vulnerability, inflammatory depression, psychosis liability, severe mental illness with nutritional deprivation, metabolic comorbidity, and cognitive frailty. Mechanistic data support plausible links with cytokine biology, the tryptophan–kynurenine pathway, dopaminergic and serotonergic systems, stress regulation, and neuroimmune homeostasis. Conclusions: Vitamin D should be conceptualized in psychiatry as a context-dependent neuroimmune and immunometabolic signal rather than a generic psychotropic intervention. Future studies should prioritize biomarker-enriched, developmentally timed, nutrition-centered models of precision prevention and adjunctive care. Full article

Background/Objectives: This study aimed to evaluate the diagnostic utility of 24 h urinary aldosterone (uAldo) measurements in patients with suspected primary aldosteronism (PA) and to explore its potential utility in guiding individualized clinical decisions. Methods: We examined 40 patients with suspected PA who underwent screening, confirmatory testing and 24 h uAldo assessment at a tertiary endocrinology center. Confirmatory tests were performed per standardized protocols. Patients were classified into three groups based on uAldo levels derived from receiver operating characteristic (ROC) analysis: Group 1 (<8.7 μg/24 h), Group 2 (8.7–13.6 μg/24 h), and Group 3 (>13.6 μg/24 h). Diagnostic performance was evaluated using sensitivity, specificity, and area under the curve (AUC). Results: uAldo levels were significantly higher in patients with positive confirmatory tests (16.3 μg/24 h vs. 5.5 μg/24 h, p < 0.001). A cut-off of >8.7 μg/24 h showed 89% sensitivity and 91% specificity (AUC: 0.95), while >13.6 μg/24 h yielded 91% sensitivity and 86% specificity (AUC: 0.97). Patients in Group 2 were managed solely with medical therapy, with no need for invasive procedures. Group 3 patients had higher blood pressure, higher uAldo levels, and more frequent hypokalemia. Adrenal venous sampling and surgery were more common in Group 3, with histological PA confirmation in all operated patients. Conclusions: The 24 h uAldo measurement demonstrated promising diagnostic performance in this cohort. The proposed cut-offs may help support patient stratification and clinical decision-making in patients with suspected PA. However, because confirmatory testing served as the reference standard, these findings should be considered exploratory and require external validation in larger multicenter studies before incorporation into routine diagnostic algorithms. Full article

Early life stress (ELS) and adverse childhood experiences are critical determinants of neurodevelopmental trajectories and long-term somatic and psychiatric health outcomes. This narrative review synthesizes current evidence, identified through searches in PubMed, Scopus, and Web of Science, on the neurobiological and epigenetic mechanisms through which early environmental exposures shape developmental programming and stress responsivity across the lifespan. A central framework is the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which mediates adaptive and maladaptive stress responses. During sensitive developmental periods, including prenatal, perinatal, and early postnatal stages, increased neuroplasticity confers heightened vulnerability to environmental influences, resulting in persistent alterations in stress regulation systems, brain circuitry, and endocrine function. The review further examines the role of maternal stress during gestation, with emphasis on placental regulatory mechanisms and fetal programming processes that establish long-term physiological set points. In parallel, emerging evidence on paternal stress is considered, highlighting potential contributions of germline epigenetic modifications and postnatal environmental transmission pathways. At the molecular level, epigenetic mechanisms—including DNA methylation, histone modifications, and non-coding RNA regulation—are discussed as key mediators linking early environmental exposures to stable changes in gene expression without alterations in DNA sequence. Collectively, the evidence supports ELS as a fundamental biological embedding process with enduring consequences for health across the lifespan. A deeper understanding of these mechanisms, alongside the identification of reliable biomarkers, is essential for early detection and the development of targeted preventive and intervention strategies in pediatric populations. Full article

Background: Atopic dermatitis is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, whereas major depressive disorder is a common psychiatric condition with a substantial impact on quality of life; increasing attention has been given to oxidative and nitrosative stress as a potential biological link between these disorders. Methods: This narrative review synthesizes current evidence on molecular biomarkers of oxidative and nitrosative stress in AD and MDD and examines shared mechanisms within the skin–brain axis. Results: Across both conditions, studies consistently report increased markers of lipid peroxidation (e.g., malondialdehyde, 4-hydroxynonenal), oxidative DNA damage (8-hydroxy-2′-deoxyguanosine), and nitrosative stress, alongside impaired antioxidant defenses, particularly involving glutathione; these alterations are closely associated with chronic inflammation, cytokine signaling, mitochondrial dysfunction, and dysregulation of neuroimmune and hypothalamic–pituitary–adrenal axis pathways. Conclusions: Although the available evidence is heterogeneous and largely based on cross-sectional studies, limiting causal inference, the findings support a biologically plausible link between AD and depression mediated by shared redox pathways and highlight the need for further longitudinal and mechanistic research. Full article

Background: Head and neck paragangliomas (HNPGLs) are rare neuroendocrine neoplasms that may be sporadic or hereditary and may occur as isolated, multifocal, or syndromic disease within the pheochromocytoma-paraganglioma spectrum. Synchronous bilateral carotid body tumors (CBTs) and bilateral vagal paragangliomas (VPGLs) are exceptional, particularly when biochemical activity and metastatic nodal involvement coexist. Case Presentation: We report a 33-year-old man with a 2-year history of enlarging bilateral neck masses, positive family history, and markedly elevated noradrenaline (6430 pg/mL; reference range <750 pg/mL). Initial CT angiography suggested bilateral CBTs, and Metaiodobenzylguanidine (MIBG) scintigraphy did not demonstrate abnormal adrenal or distant uptake. After alpha- and beta-blockade, staged surgery was performed. Right CBT excision demonstrated metastatic PGL, with two of four lymph nodes positive. Subsequent MRI and operative reassessment revealed synchronous bilateral CBTs and bilateral VPGLs. Left-sided surgery required partial debulking of a vagal-adherent mass to preserve nerve continuity; pathology confirmed PGL with Ki-67 index approximately 2% and left neck nodes were negative. Postoperatively, profound bradycardia required temporary then permanent pacing, together with bilateral vocal cord paralysis. During follow-up, swallowing and voice improved, the pacemaker was removed, and late imaging showed stable residual cervical disease without visceral metastasis on chest/abdominal CT. Conclusions: This case highlights the diagnostic and therapeutic complexity of multicentric, biochemically active HNPGLs and supports individualized multidisciplinary management, genetic counseling, biochemical surveillance, and long-term follow-up. Full article