Search Results (601)

Depression is one of the most common mental disorders in modern society, and it has become a serious threat to human health. The limitations of existing antidepressant drugs have prompted people to turn to the multi-target, low-toxic side effects of natural products. This article reviews the conventional nutrients (omega-3 fatty acids, folic acid, and mineral elements) and functional active ingredients (flavonoids, polysaccharides, saponins, and terpenoids) in medicinal and food homologous substances (MFHs). They show antidepressant potential by regulating neurotransmitters, improving hypothalamic–pituitary–adrenal (HPA) axis function, promoting neuroplasticity, inhibiting neuroinflammation, regulating ferroptosis, and interfering with the gut–brain axis. In addition, this paper discusses the application prospects of modern technologies such as microbial fermentation and nano-delivery in improving the bioavailability of MFHs and product development. In summary, MFHs have potential application value in dietary intervention and adjuvant therapies for depression; in the future, randomized controlled clinical trials should be strengthened, and multi-omics technology should be combined to promote the development of precision products so as to provide a new perspective for the development of new antidepressant drugs. Full article

The relationship between stress and Parkinson’s disease is regarded as complex and multifaceted, although a direct causal link has not yet been conclusively proven. One prevailing hypothesis is based on the activation of the hypothalamic–pituitary–adrenal (HPA) axis and the consequent elevation of glucocorticoid levels. Prolonged exposure to these hormones may exacerbate oxidative stress, thereby rendering the dopaminergic neurons within the brain’s subcortical structures more susceptible to degeneration. Furthermore, stress may intensify neuroinflammation through the activation of microglia—a mechanism that could constitute a significant factor in the pathogenesis of Parkinson’s disease. Another important concept concerns the direct interaction of stressors with the dopaminergic system. Physiological and psychological stress can alter dopaminergic transmission by affecting both the synthesis and release of dopamine, as well as the sensitivity of dopamine receptors. Severe or chronic stress may contribute to the disruption of dopaminergic mechanisms and accelerate the onset of clinical symptoms in predisposed individuals. Furthermore, many researchers draw attention to the role of stress-induced aggregation of α-synuclein—a key protein implicated in the pathogenesis of Parkinson’s disease. Clinical data suggest a highly probable link between post-traumatic stress disorder and an increased risk of developing Parkinson’s disease, although these findings remain inconclusive. It is possible that stress acts not as a primary cause, but rather as a modifying factor that interacts with genetic predisposition, accelerating or triggering neurodegenerative processes. The aim of our narrative review was to examine these concepts and discuss possible directions for future research into the interaction between stress and Parkinson’s disease. Full article

The high comorbidity between autism spectrum disorder (ASD) and major depressive disorder (MDD) represents a complex and heterogeneous clinical challenge. Although elevated rates of depression in autistic individuals are well documented, the neurobiological and psychosocial mechanisms underlying this overlap remain debated, particularly in adulthood. This review synthesizes convergent evidence from genetics, monoaminergic and glutamatergic neurotransmission, neuroinflammatory signaling, hypothalamic–pituitary–adrenal axis dysregulation, large-scale brain network alterations, and gut–brain axis modulation to clarify the biological and psychosocial pathways contributing to ASD–depression comorbidity. In addition to shared neurobiological vulnerability, cumulative environmental stressors such as chronic social masking, stigma, and structural barriers may amplify depressive risk across the lifespan. We propose a hypothesis-generating framework that integrates these findings into a mechanistic stratification model, linking dominant biological profiles to targeted therapeutic hypotheses. Within this preliminary model, plant-derived compounds and microbiota-targeted interventions are hypothesized to serve as promising adjunctive strategies, particularly in neuroinflammatory and stress-related subtypes, complementing established pharmacological and neuromodulatory treatments. By moving beyond descriptive overlap toward biologically informed stratification, this review aims to support precision-guided and neurodiversity-affirming approaches for the assessment and treatment of depression in autistic individuals, especially adults who bear a disproportionate burden of mood disorders. This narrative review is based on a structured literature search conducted in PubMed, Scopus, and Web of Science using combinations of keywords such as “autism spectrum disorder,” “major depressive disorder,” “neuroinflammation,” and “gut–brain axis. Full article

The timing and nature of gestational stress can alter offspring immune function and hypothalamic–pituitary–adrenal (HPA) axis regulation, yet the role of maternal stress history remains poorly understood. This study evaluated the effects of prenatal stress, maternal stress history, and repeated stress exposure on immune and stress reactivity in prenatally stressed (PS) gilts across two farrowings. Eleven PS second-parity sows (197.27 ± 19.22 kg) were sampled at multiple timepoints and compared with their maternally stressed (MS) dams. During the second pregnancy, PS sows received the same maternal treatment as their dams: placebo (CON) or hydrocortisone acetate (HCA) administered twice daily for 21 days during mid (M; d 51–72) or late (L; d 81–102) gestation. Data were analyzed using mixed models with repeated measures in SAS (Version 9.4). During the first pregnancy, PS gilts in the L-HCA group exhibited higher lymphocyte proliferation indices and plasma cortisol concentrations than MS dams (p < 0.05). In the second pregnancy, dehydroepiandrosterone sulfate concentrations were lower in PS sows in the M-HCA group than the CON sows (p < 0.05). Overall, cortisol concentrations were lower in PS sows than PS gilts (p < 0.05), suggesting that maternal stress history modifies physiological responses to gestational stress, though this interpretation is constrained by the small sample size. Full article

Exercise-induced hypoalgesia (EIH) illustrates how physical activity can reshape the biology of pain while simultaneously influencing the systems that regulate stress. Acute and repeated exercise can reduce pain sensitivity in healthy individuals and in some chronic pain populations, yet the magnitude and consistency of these effects vary substantially across individuals, diagnoses, and exercise protocols. This variability suggests that EIH is not a uniform response, but an adaptive multisystem process shaped by neural, immune, endocrine, metabolic, musculoskeletal, and psychosocial factors. This narrative review synthesizes evidence linking pain modulation and stress regulation across biological scales. Exercise engages descending pain modulatory circuits involving the periaqueductal gray, rostral ventromedial medulla, and spinal dorsal horn, while also influencing endogenous opioid, endocannabinoid, serotonergic, and noradrenergic signaling. These pathways are relevant not only to nociceptive inhibition, but also to affective regulation, hypothalamic–pituitary–adrenal axis activity, autonomic balance, and perceived stress. In parallel, exercise-related neuroimmune changes, including modulation of microglial activity, cytokine signaling, and myokine release from skeletal muscle, may connect peripheral metabolic activity with central mechanisms of pain and stress adaptation. Importantly, the evidence supporting these mechanisms differs in strength: some findings derive from human experimental and clinical studies, whereas others are supported mainly by preclinical or translational research. By distinguishing direct evidence from mechanistic inference, this review highlights how exercise may support hypoalgesia, stress resilience, and functional recovery, while also emphasizing the need for biomarker-informed, personalized exercise strategies in chronic pain management. Full article

Background/Objectives: Contrast-associated acute kidney injury (CA-AKI) is a frequent complication after coronary angiography (CAG) that may adversely affect outcomes in patients with acute coronary syndrome (ACS). We aimed to estimate the incidence of CA-AKI and evaluate its association with 30-day all-cause mortality in adults with ACS undergoing CAG. Methods: We conducted a retrospective cohort study; CA-AKI was defined as an increase in serum creatinine ≥0.5 mg/dL or ≥25% from baseline within 72 h after contrast exposure, according to KDIGO criteria. The primary outcome was 30-day all-cause mortality. Survival analyses were performed using Kaplan–Meier curves and Cox proportional hazards models. Results: Including 374 consecutive adults with ACS who underwent diagnostic or therapeutic CAG at a tertiary referral center. The mean age was 68.8 ± 11.2 years, and 72.6% were male. CA-AKI occurred in 17.4% of patients, and 11.7% died within 30 days. In multivariable analysis, age (HR 1.04; 95% CI 1.00–1.07), CA-AKI (HR 2.81; 95% CI 1.48–5.33), stress hyperglycemia ≥180 mg/dL (HR 2.88; 95% CI 1.54–5.38), and delirium (HR 7.20; 95% CI 2.40–20.92) were independent predictors of mortality. Conclusions: age, CA-AKI, stress hyperglycemia, and delirium independently predict short-term mortality after CAG in ACS, supporting integrated risk-stratified peri-procedural management. These observations suggest that mortality in these patients may be related to an inflammatory process secondary to ischemia/reperfusion, which is probably induced by dysregulation of the central autonomic network and activation of the hypothalamic–pituitary–adrenal axis which is currently underdiagnosed. Full article

Introduction: Depression and anxiety are highly prevalent disorders with a substantial impact on quality of life. Limitations related to the efficacy and tolerability of conventional pharmacological treatments have stimulated increasing interest in complementary therapeutic approaches, including phytotherapy. This review aims to provide an integrative analysis of some plant species present in the spontaneous flora of Romania, correlating their traditional use with the phytochemical, pharmacological, preclinical, and clinical data available globally. The approach aims to highlight the therapeutic relevance of these species in both regional and international contexts. Relevant sections: This narrative review integrates available data on seven species commonly used in traditional medicine: Matricaria chamomilla L., Galium odoratum L., Melissa officinalis L., Leonurus cardiaca L., Hypericum perforatum L., Tilia spp., and Crataegus monogyna Jacq. This review examines their geographical distribution, taxonomic classification, phytochemical composition, proposed mechanisms of action, and available preclinical and clinical evidence, as well as safety considerations and products currently available on the Romanian pharmaceutical sales. Discussion: Current evidence suggests that Hypericum perforatum L. and Melissa officinalis L. are supported by relatively robust clinical data regarding their efficacy in reducing anxiety and depressive symptoms. For the remaining species, evidence is derived mainly from preclinical studies or traditional use. The proposed mechanisms of action include modulation of neurotransmitter activity, antioxidant and anti-inflammatory effects, and regulation of the hypothalamic–pituitary–adrenal (HPA) axis. Conclusions: Phytotherapy represents a promising approach in the management of anxiety and depressive disorders, particularly as a complementary therapeutic option. However, the strength of evidence varies considerably among the analyzed species, and clinical data remain limited for several of them. Future directions: From a future perspective, advancing the clinical relevance of the analyzed plant species requires a more coherent integration of existing pharmacological, preclinical, and emerging clinical data. Particular attention should be given to species for which the current evidence remains predominantly experimental, by promoting research strategies that facilitate the translation of mechanistic findings into clinically meaningful outcomes. Full article

Keloids and hypertrophic scars are fibroproliferative disorders of wound healing characterized by excessive extracellular matrix deposition, constant inflammation, and high recurrence rates despite appropriate management. Conventional therapies, including surgical excision, corticosteroid injections, laser therapy, and radiation, can provide temporary relief. However, treatment failure remains common, specifically in refractory keloids. Recent findings suggest these outcomes cannot be fully explained by technical or mechanical factors alone, and pathological scarring may reflect underlying immune and neuroimmune dysfunction. Current evidence shows prolonged activation of pro-inflammatory and pro-fibrotic cytokine pathways like IL-6, TNF-α, TGF-β, and IL-17 drives sustain fibroblast activation and disrupts normal wound healing and remodeling. Additionally, the skin functions as an integrated neuro-endocrine-immune organ, allowing bidirectional communication between cutaneous nerves, immune cells, and stromal tissue. Neurogenic inflammation is mediated by neuropeptides, mast cell activation, and stress-induced hypothalamic–pituitary–adrenal axis dysregulation, which further amplifies inflammation within scar tissue. Psychiatric comorbidities like depression, anxiety, and chronic psychological stress serve as a positive feedback mechanism and are increasingly recognized as biologically active contributors to immune dysregulation. This review highlights critical gaps in current management strategies and emphasizes the need for biologically informed, multidisciplinary approaches to improve long-term outcomes for keloid and hypertrophic scar management. Full article

Background: Gestation is a period of significant biological plasticity where the intrauterine environment influences fetal development via “fetal programming”. This study systematically reviews and meta-analyzes the association between genetic determinants—specifically the NR3C1, FKBP5, and CRHR1 genes, chosen for their pivotal role in the functional regulation and feedback sensitivity of the hypothalamic–pituitary–adrenal (HPA) axis—and stress reactivity during pregnancy. Methods: Following PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, and Web of Science, yielding an initial total of 1430 records. After removing duplicates and screening 669 studies, a total of 34 primary observational studies were included in the systematic review and qualitative synthesis. For the quantitative synthesis, 27 articles provided sufficient data, resulting in k = 39 independent effect sizes analyzed via a mixed-effects model to account for tissue-specific and cohort-specific outcomes. Results: Systematic analysis reveals that maternal psychosocial stress significantly correlates with NR3C1 hypermethylation, acting as a biological mediator for neonatal cortisol dysregulation and hippocampal volume reduction. The FKBP5 rs1360780 polymorphism emerged as a key moderator of structural vulnerability, showing a “double-hit” effect when combined with epigenetic alterations. Furthermore, the study identifies sex-specific susceptibility, with divergent placental trajectories for male and female fetuses. Meta-analytic estimates confirmed the robustness of these associations (Rosenthal Fail-Safe N = 431,000), despite a general trend toward statistical significance (p = 0.079) in heterogeneous cohorts. Conclusions: The findings underscore a stable link between genetic determinants and prenatal stress reactivity. The interaction between molecular predisposition and environmental factors defines the health of the mother–infant dyad. These results advocate for a transition toward Precision Prenatal Medicine, integrating polygenic risk scores and epigenetic monitoring to implement early, targeted preventive interventions. Full article

The skin–brain axis constitutes a complex, bidirectional network integrating cutaneous sensory, immune, and neuroendocrine systems with central neural circuits involved in emotion regulation, stress responsivity, and social cognition. Advances in psychodermatology and cosmetic science have progressively extended this framework to the emerging field of neurocosmetics, which explores how topical formulations, sensorial properties, and cutaneous neuromodulators may influence psychological well-being, affective states, and perceived stress. The aim of this narrative review is to synthesize current evidence on the biological foundations of the skin–brain axis and to critically examine the implications of these mechanisms for neurocosmetic interventions from a psychological and psychiatric perspective. It describes the biological substrates underlying skin–brain communication, including the cutaneous hypothalamic–pituitary–adrenal axis, neuropeptides, neurotrophins, transient receptor potential channels, and endocannabinoid signaling, and examines how these pathways are targeted by neurocosmetic interventions. Particular attention is devoted to neuroactive compounds, such as peptides, cannabinoids, botanicals, and aromatherapeutic molecules, as well as to sensorial strategies involving texture, temperature, and olfactory cues, which may modulate mood, anxiety, and self-perception through peripheral mechanisms. From a psychological and psychiatric perspective, the review discusses the intersection between stress-related skin conditions, body image disturbances, and emotional dysregulation, highlighting how cosmetic practices may influence subjective well-being beyond purely aesthetic outcomes. Methodological limitations of the existing literature, including the heterogeneity of study designs and outcome measures, as well as ethical considerations related to mood- and stress-related claims in cosmetic products, are critically examined. Finally, future research directions are outlined, and a translational framework is proposed to integrate dermatology, neuroscience, and mental health within next-generation cosmetic science. Full article

Environmental chemicals are rarely considered stressors in the way that psychological or physical stressors are. Yet many endocrine-disrupting chemicals (EDCs) interact with the body’s core stress response system. This review examines how EDCs alter hypothalamic–pituitary–adrenal (HPA) regulation and how biological sex influences those responses. Drawing on human epidemiological data and experimental models, we describe how EDC exposure affects cortisol dynamics, feedback sensitivity, and adrenal signaling, with a particular focus on sex-dependent outcomes. We propose the concept of endocrine noise to describe how low-dose, often mixed EDC exposures introduce persistent interference into hormone signaling without necessarily causing overt endocrine deficiency or excess. In this framework, EDCs act as chronic, low-grade stressors that reset the timing, feedback precision, and rhythmic organization of the HPA axis rather than as isolated reproductive toxicants. We argue that EDCs should be understood as chronic, context-dependent stress modifiers that reshape sex-specific “risk architectures” for affective, metabolic, and immune disorders. Recognizing sex-specific HPA architecture and endocrine noise has immediate implications for study design and regulation, including the need for sex-stratified analyses, circadian-sensitive sampling of cortisol, and risk assessments that consider how the same exposure can push female and male stress systems in divergent directions. Full article

Chronic diseases increasingly reflect a shared biological origin: persistent cellular stress. This review summarizes the biochemical mechanisms that normally preserve cellular homeostasis, namely redox regulation, endoplasmic reticulum proteostasis, mitochondrial quality control, autophagy, and DNA damage response, and explains how they fail under sustained lifestyle-related overload. Repeated exposure to psychological stress, sleep disruption, hypercaloric intake, and physical inactivity shifts adaptive signaling toward maladaptation, promoting oxidative damage, protein misfolding, mitochondrial dysfunction, low-grade inflammation, and genomic instability. These interconnected processes contribute to the development and progression of major chronic non-communicable diseases, including obesity, type 2 diabetes, cardiovascular disease, neurodegeneration, and cancer. Particular emphasis is placed on circadian and neuroendocrine regulation, especially overactivation of the hypothalamic–pituitary–adrenal axis and impaired nocturnal regenerative pathways such as glymphatic clearance and DNA repair. Together, the evidence supports a unifying model in which chronic pathology emerges from cumulative failure of cellular resilience systems rather than isolated organ-specific defects. This perspective highlights sleep optimization, stress reduction, and metabolic regulation as mechanistically grounded strategies for prevention and supportive interventions for chronic disease. Full article

Background/Objectives: Acute pancreatitis (AP) lacks disease-modifying pharmacotherapy. Neuroimmune, serotonergic, and redox-regulated pathways may modulate inflammatory amplification and acinar injury, although pharmacovigilance data link some psychotropic drug classes to AP risk. This review synthesized controlled rodent studies evaluating neuromodulatory interventions with serotonergic, stress-axis, or ferroptosis-linked targets in experimental AP. Methods: PubMed, Scopus, eLIBRARY.ru, and Elicit were searched in January 2026, supplemented by Google Scholar audit and citation chasing. Eligible studies were controlled in vivo rodent experiments using validated AP models with quantitative outcomes. Intervention timing was classified a priori as a primary analytic variable. Risk of bias was assessed with SYRCLE. A prespecified audit showed that no subset met the criteria for quantitative pooling because of heterogeneity in model class, compounds, timing, outcome definitions, units, and sampling timepoints. Mechanism-stratified qualitative synthesis was therefore performed. The protocol was registered on OSF (doi: 10.17605/OSF.IO/CZXDJ). Results: Nine studies (1992–2023) yielded 410 outcome rows across three mechanistic strands. Serotonergic modulation (5-HT₂/5-HT₂A-focused; six studies) reduced serum amylase/lipase (−37% to −65% vs. disease controls) and histological injury, with receptor-selectivity data supporting 5-HT₂A-mediated mechanisms. Stress-axis modulation with thiadiazine L-17 reduced 7-day mortality in two severe models (from 50–70% to 30%). Olanzapine attenuated ferroptosis-linked injury via off-target antioxidant activity independent of serotonergic receptors. All interventions were prophylactic, peri-induction, or very early post-induction; no delayed therapeutic-window studies were identified. Most SYRCLE domains were unclear, particularly allocation concealment and blinding-related procedures. Conclusions: Neuromodulatory pathways modulate experimental AP in rodents, but evidentiary strength differs across mechanistic strands. Inference is constrained by absent therapeutic-window testing, heterogeneous endpoints, and reporting deficits. The findings support mechanism-level target prioritization rather than clinical repurposing. Full article

Background: Dermatological conditions represent a leading cause of global nonfatal disease burden, accounting for approximately 42.9 million disability-adjusted life years annually. Their complex pathogenesis is increasingly understood through the skin–brain–exposome axis, a bidirectional neuroimmunological and environmental communication network. The study aims to synthesize the neurobiological mechanisms of the skin–brain–exposome axis with macroscopic sociodemographic modifiers, clinical manifestations, and evidence-based psychodermatological interventions. Methods: A narrative review was conducted, following a structured search of PubMed, Scopus, and Web of Science (from inception to February 2026), yielding 54 sources. Mechanistic and interventional data (including randomized controlled trials and meta-analyses) were integrated with large-scale population-based epidemiological findings, anchored by a recent cross-sectional Polish cohort of 27,000 adults. Results: Psychological distress is associated with hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis and peripheral neurogenic inflammation (e.g., Substance P, corticotropin-releasing hormone), exacerbating stress-sensitive conditions such as atopic dermatitis, psoriasis, acne, and chronic pruritus. External exposome factors (urbanization, pollution) and sociodemographic variables (education, gender) may modify biological risk and diagnostic capture rates, frequently generating an epidemiological diagnostic paradox. Randomized trials support that psychotherapeutic interventions, particularly Cognitive Behavioral Therapy (CBT) and Mindfulness-Based Stress Reduction (MBSR), effectively disrupt the physical itch–scratch–stress cycle and improve disease-specific quality of life, serving as evidence-based adjunctive strategies in comprehensive care. Conclusions: Effective dermatological management requires targeting both the cutaneous barrier and the psychological exposome. Integrating routine psychosocial screening and stratified behavioral interventions into standard clinical care is essential for addressing the neuroimmune chronicity of inflammatory skin diseases. Full article

Alzheimer’s disease (AD) is primarily recognized for progressive cognitive decline driven by beta-amyloid accumulation and tau pathology. However, many individuals with AD also experience chronic pain and depressive symptoms, which significantly impair daily functioning and quality of life and increase caregiver burden. These non-cognitive features are frequently underrecognized, despite evidence suggesting they share overlapping biological pathways with neurodegeneration. Emerging data highlight the role of neuroinflammation, oxidative stress, hypothalamic–pituitary–adrenal axis dysregulation, and endocannabinoid system alterations in linking AD pathology to disturbances in pain processing and mood regulation. Persistent microglial activation, cytokine imbalance, redox disruption, and chronic stress signaling may simultaneously promote neuronal vulnerability while shaping affective and nociceptive responses. This review synthesizes current preclinical and clinical evidence on the interplay between pain, depression, and AD, emphasizing their shared pathophysiological mechanisms and clinical relevance. Recognizing these symptoms as integral components of disease progression, rather than isolated comorbidities, can inform the development of integrated, multidimensional therapeutic strategies in AD care. Full article