Search Results (139)

Background: Population aging increases susceptibility to cognitive decline, anxiety, and metabolic dysregulation, yet safe and effective interventions remain limited. Saffron (Crocus sativus L.) has been traditionally used to enhance mood and cognition, and its main metabolites, crocins and safranal, exert neuroprotective, anxiolytic, and metabolic effects. However, variability in extract composition and frequent adulteration hinder reproducibility. Objectives: To clarify the efficacy of genuine saffron preparations in aging, we investigated a saffron extract standardized for safranal and crocin content (SSE). Methods: Safranal bioavailability was first characterized in rats, followed by an evaluation of behavioral, neuroendocrine, and metabolic outcomes after 35 days of oral SSE administration (25 or 200 mg/kg/day) in 25-month-old male C57BL/6 mice. Behavioral performance was assessed using open field and novel object recognition tests, while molecular analyses targeted neuropeptides in the hypothalamus and amygdala, hippocampal plasticity markers, cortical inflammatory proteins, and hepatic lipid metabolism genes. Results: SSE administration induced a rapid but transient increase in the plasma’s safranal, confirming its bioavailability. In aged mice, the low dose prevented age-related weight loss and modulated hepatic lipid metabolism, whereas the high dose reduced anxiety-like behavior and improved recognition memory. The anxiolytic effects are consistent with elevated hypothalamic Npy, an anxiolytic peptide, reduced amygdalar Crh, a key mediator of stress and anxiety, and decreased hypothalamic Hcrt, an arousal modulator. The improvement in memory is associated with modulation of the cortical and hippocampal inflammatory and endocannabinoid proteins involved in neural plasticity. Conclusions: These findings highlight content-standardized saffron extracts as a promising multi-target nutraceuticals for healthy aging. Full article

Women exhibit a higher prevalence of depression, anxiety, stress-related disorders, and autoimmune conditions compared to men, yet the biological mechanisms underlying this sex difference remain incompletely understood. Growing evidence identifies neuroinflammation as a central mediator of psychiatric vulnerability in women, shaped by interactions between sex hormones, immune activation, and neural circuit regulation. Throughout the female lifespan, fluctuations in estrogen and progesterone, such as those occurring during puberty, the menstrual cycle, pregnancy, postpartum, and perimenopause, modulate microglial activity, cytokine release, and neuroimmune signaling. These hormonal transitions create windows of heightened sensitivity in key brain regions involved in affect regulation, including the amygdala, hippocampus, and prefrontal cortex. Parallel variations in systemic inflammation, mitochondrial function, and hypothalamic–pituitary–adrenal (HPA) axis responsivity amplify stress reactivity and autonomic imbalance, contributing to increased risk for mood and anxiety disorders in women. Emerging data also highlight sex-specific interactions between the immune system and monoaminergic neurotransmission, gut–brain pathways, endothelial function, and neuroplasticity. This review synthesizes current neuroscientific evidence on the sex-dependent neuroinflammatory mechanisms that bridge hormonal dynamics, brain function, and psychiatric outcomes in women. We identify critical periods of vulnerability, summarize converging molecular pathways, and discuss novel therapeutic targets including anti-inflammatory strategies, estrogen-modulating treatments, lifestyle interventions, and biomarkers for personalized psychiatry. Understanding neuroinflammation as a sex-specific process offers a transformative perspective for improving diagnosis, prevention, and treatment of psychiatric disorders in women. Full article

Background/Objectives: Anxiety disorders (ADs) affect up to 20% of mothers in the postpartum period, characterized by psychological symptoms (e.g., emotion dysregulation; ER) and physical symptoms (e.g., disrupted bodily awareness). Although Cognitive Behavioural Therapy effectively reduces anxiety and mood symptoms, it shows limited efficacy in addressing ER difficulties and rarely targets interoceptive dysfunction—both common in postpartum ADs. This study evaluates the effectiveness of a brief mindfulness-based intervention in improving anxiety, ER, and interoception in mothers with postpartum ADs. A secondary aim is to examine changes in brain connectivity associated with these domains. Methods: This protocol describes a proof-of-concept randomized controlled trial involving 50 postpartum mothers with ADs. Participants will be randomized to receive either a 4-week mindfulness intervention plus treatment-as-usual (TAU) or TAU alone. Participants in the mindfulness + TAU group will complete a virtual 4-week group intervention adapted from Mindfulness-Based Cognitive Therapy. The TAU group will receive usual care for 4 weeks and then be offered the mindfulness intervention. Self-report measures of anxiety, ER, and interoception will be collected at baseline, post-intervention, and at a 3-month follow-up. Resting-state functional MRI will be conducted at baseline and post-intervention to assess functional connectivity changes. This trial has been registered on ClinicalTrials.gov (NCT07262801). Results: Improvements in anxiety, ER, and interoception are anticipated, along with decreased default mode network, and increased salience network connectivity post-intervention is hypothesized. Conclusions: This study will be the first to examine the combined psychological and neural effects of mindfulness in postpartum ADs, offering a potentially scalable mind–body treatment. Full article

Background: Growing evidence indicates that oral microbiome dysbiosis contributes to systemic inflammation, immune activation, and neural dysfunction. These processes may influence the onset and progression of major neuropsychiatric and neurodegenerative disorders. This review integrates clinical, epidemiological, and mechanistic findings linking periodontal pathogens and oral microbial imbalance to Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, and anxiety. Methods: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify recent studies examining alterations in the oral microbiota, microbial translocation, systemic inflammatory responses, blood–brain barrier disruption, cytokine signaling, and neural pathways implicated in brain disorders. Results: Evidence from human and experimental models demonstrates that oral pathogens, particularly Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, can disseminate systemically, alter immune tone, and affect neural tissues. Their virulence factors promote microglial activation, cytokine release (IL-1β, IL-6, TNF-α), amyloid-β aggregation, and α-synuclein misfolding. Epidemiological studies show associations between oral dysbiosis and cognitive impairment, motor symptoms in PD, and alterations in mood-related taxa linked to stress hormone profiles. Immunometabolic pathways, HPA-axis activation, and the oral–gut–brain axis further integrate these findings into a shared neuroinflammatory framework. Conclusions: Oral dysbiosis emerges as a modifiable contributor to neuroinflammation and brain health. Periodontal therapy, probiotics, prebiotics, synbiotics, and targeted inhibitors of bacterial virulence factors represent promising strategies to reduce systemic and neural inflammation. Longitudinal human studies and standardized microbiome methodologies are still needed to clarify causality and evaluate whether restoring oral microbial balance can modify the course of neuropsychiatric and neurodegenerative disorders. Full article

The microbiota–gut–brain axis (MGBA) comprises a complex bidirectional communication network integrating neural, immune, metabolic, and endocrine pathways. Dopamine, traditionally viewed as a central neurotransmitter, also plays essential roles in the gastrointestinal (GI) tract, where it regulates motility, secretion, barrier homeostasis, and mucosal immunity. Growing evidence indicates that the gut microbiota significantly contributes to intestinal dopamine metabolism through specialized enzymatic pathways, particularly tyrosine decarboxylase in Enterococcus species and catechol dehydroxylase in Eggerthella species. These microbial reactions compete with host processes, alter dopaminergic tone, and degrade orally administered levodopa (L-DOPA), providing a mechanistic explanation for the variability in treatment response in Parkinson’s disease (PD). Beyond PD, microbially mediated alterations in dopaminergic signaling have been implicated in mood disorders, neurodevelopmental conditions, metabolic dysfunction, and immune-mediated diseases. This review synthesizes current mechanistic and translational evidence on the dopamine–microbiota interface, outlines microbial pathways shaping dopaminergic activity, and highlights therapeutic opportunities including microbiota modulation, dietary strategies, fecal microbiota transplantation, and targeted inhibitors of microbial dopamine metabolism. Understanding this interface offers a foundation for developing personalized approaches in neurogastroenterology and neuromodulatory therapies. Full article

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder linked to impaired cognition and altered dopamine neurotransmission. Emerging evidence suggests that women with ADHD experience pronounced hormone-related difficulties, with menstrual cycle-related changes in mood and cognition interfering with daily functioning and diminishing treatment efficacy. This review examines the influence of hormonal fluctuations during the menstrual cycle on cognitive functioning and ADHD symptomatology in women. A comprehensive literature search of Ovid EmBase identified studies published between 2015 and 2025 examining cognitive performance, including attention, executive functioning, working memory, and inhibitory control, across menstrual cycle phases in women with or without ADHD. Twenty-nine studies met inclusion criteria. Neurobiological measurements included hormonal assays, neuroimaging, and neurotransmitter models. Seven studies in non-clinical populations suggested that attentional processing was enhanced during the mid-luteal phase, which may be linked to higher progesterone levels. By contrast, four studies in women with ADHD and six studies in women with mood-related disorders, such as PMS or PMDD, consistently observed impairments in attention, executive function, and impulsivity during the mid-luteal and pre-menstrual phases. These objective findings parallel subjective reports of worsened cognition, heightened mood symptoms, and diminished medication efficacy during the luteal phase. Current evidence indicates that ADHD-related cognitive functioning fluctuates with the menstrual cycle, with impairments particularly evident in women with ADHD and/or comorbid mood disorders. These changes may reflect increased sensitivity to allopregnanolone, peri-menstrual oestrogen withdrawal, and the absence of compensatory neural adaptations observed in non-clinical populations. However, findings remain preliminary and sometimes contradictory due to methodological heterogeneity and small sample sizes. Further research is needed to clarify these mechanisms and, importantly, to translate theoretical insights into clinical application through female-specific diagnostic procedures and treatment strategies. Full article

Background/Objectives: Obesity and insulin resistance (IR) increase the risk of mood disorders, which often manifest during young adulthood. However, neuroelectrophysiological investigations of whether adiposity and IR modify electrocortical activity and emotional processing outcomes remain underexplored, particularly in young adults. Therefore, this study used electroencephalography (EEG) to investigate whether obesity and/or IR moderate the relationships between brain potentials and affective processing in younger adults. Methods: Thirty younger adults completed a passive picture-viewing task utilizing the International Affective Picture System while real-time electroencephalography was simultaneously recorded. Two event-related potentials—early posterior negativity (EPN) and late positive potential (LPP)—were quantified. Affective processing parameters included mean valence ratings and stimulus-to-response-onset reaction times in response to unpleasant, pleasant, and neutral images. Body fat percentage and Homeostatic Model Assessment for Insulin Resistance values were measured. Hierarchical moderated regression analysis was utilized to test the interrelationships between brain potentials, adiposity, IR, and affective processing. Results: In the Negative−Neutral condition, lean and insulin-sensitive participants gave less negative valence ratings to unpleasant versus neutral images when late-window LPP amplitudes were larger, whereas this relationship was reversed in participants with obesity and absent in those with IR. Contrariwise, neither obesity nor IR moderated LPP responses to affective processing parameters in the Positive−Neutral or Negative−Positive valence conditions. Additionally, obesity and IR did not moderate the links between EPN responses and affective processing parameters in any of the valence conditions. Conclusions: Lean, insulin-sensitive young adults showed attenuated affective processing of unpleasant stimuli through stronger neural responses, whereas neural responses to pleasant stimuli did not vary across levels of body fat or IR. These preliminary findings suggest that both obesity and IR increase the vulnerability to mood disorders in young adulthood. Full article

Background/Objectives: Regular physical activity (PA) benefits mood and cognition, yet the neural markers associated with free-living PA remain unclear. Alpha asymmetry (AA), a neural marker of affective and motivational states, may help predict individuals’ preferred activity intensity and duration. To examine the relationship between resting-state AA in frontal and parietal regions, positive affect, and accelerometer-derived PA metrics were measured. Methods: Fifty-nine participants (age = 21.8 years) wore wrist accelerometers for 7 days, completed resting-state electroencephalography (EEG; alpha power 8–13 Hz), and completed the Positive and Negative Affect Schedule (PANAS). PA metrics included sedentary time (ST), light PA (LPA), moderate-to-vigorous PA (MVPA), average acceleration (AvAcc), intensity gradient (IG), and the most active X minutes (M2–M120). Multiple regression models tested AA to PA associations while accounting for sex and positive affect. Results: Although frontal AA was included as a key neural candidate, the observed associations emerged only at parietal sites. Greater right parietal AA power was associated with the most active M60, M30, M15, M10, and M5. For IG, greater AA power was observed in the left parietal region. No significant associations emerged for LPA, MVPA, AvAcc, M120, or M2. Across models, higher positive affect consistently predicted greater PA engagement. Conclusions: While resting frontal AA is theoretically relevant to motivational processes, the findings indicate that parietal AA more strongly differentiates individuals’ tendencies toward specific PA intensities and durations. Positive affect is associated with PA engagement. These findings identify parietal AA as a promising neural correlate for tailoring PA strategies aimed at sustaining active lifestyles. Full article

Chronic psychological stress impairs neuroendocrine balance and increases the risk of mental health disturbances, including anxiety, sleep disruption, and low mood. The gut–brain axis has emerged as a promising target for stress modulation, particularly through psychobiotic interventions. This randomized, double-blind, placebo-controlled trial evaluated the effects of a combined psychobiotic formulation (Neuralli Mood), comprising live Lactiplantibacillus plantarum PS128 (PS128) and heat-treated Lacticaseibacillus paracasei PS23 (HT-PS23), on the psychological and physiological stress responses in a high-stress occupational population. A total of 116 healthy participants with elevated perceived stress (PSS ≥ 14), primarily firefighters, were randomly assigned to receive the dual-strain supplement or placebo for 8 weeks. Stress-related outcomes were assessed by using validated psychological scales and serum biomarkers. Compared with placebo, the psychobiotics group showed significantly greater reductions in overall job stress perception (JSS), state anxiety (STAI), and insomnia severity (ISI) (all p < 0.05). Additionally, serum adrenocorticotropic hormone (ACTH) and norepinephrine levels were significantly reduced post-intervention, whereas cortisol levels remained unchanged. These findings suggested that combining live and heat-treated psychobiotic strains may provide a safe and effective strategy for alleviating psychological stress and regulating neuroendocrine function in high-risk populations. Full article

Background: The gut microbiota plays a crucial role in brain development and function, especially in early life. Disruptions in the pediatric microbiota–gut–brain axis have been linked to neurodevelopmental and psychiatric disorders. We hypothesize that early-life dysbiosis can perturb neurodevelopment via the pediatric microbiota–gut–brain axis, increasing risk and/or severity of neuropsychiatric outcomes, and that microbiota-targeted strategies may mitigate this risk. Methods: We conducted a narrative review by searching PubMed, Scopus, and Web of Science up to January 2025 for studies addressing pediatric microbiota, neuropsychiatric development, and interventions. Human and animal studies were included if they provided mechanistic or clinical insights. Results: Key determinants of microbiota development in childhood include mode of delivery, feeding practices, antibiotic exposure, diet, and environment. Altered microbial composition has been associated with autism spectrum disorder, attention-deficit/hyperactivity disorder, mood disorders, anxiety, and anorexia nervosa. Mechanistic pathways involve immune modulation, neural signaling (including the vagus nerve and enteric nervous system), and microbial metabolites such as short-chain fatty acids. Interventions targeting the microbiota—ranging from dietary strategies and probiotics to psychobiotics and fecal microbiota transplantation—show promise but require further pediatric-focused trials. Conclusions: The pediatric microbiota–gut–brain axis represents a critical window for neuropsychiatric vulnerability and intervention. Early-life strategies to support a healthy microbiota may help reduce the risk or severity of psychiatric disorders. Future research should prioritize longitudinal pediatric cohorts and clinical trials to translate mechanistic insights into precision interventions. Full article

Background: Depression and anxiety disorders impact millions globally. In recent years, low-intensity focused ultrasound (LIFU), characterized by its high precision, deep penetration, and non-invasive nature, has garnered significant interest in neuroscience and clinical practice. To enhance understanding of its effects on mood, therapeutic availability in treatment of depression/anxiety disorders, and potential mechanisms, a systematic review of studies investigating the emotional impact of LIFU on depressive/anxious-like animal models, healthy volunteers, and patients with depression or anxiety disorders has been undertaken. Methods: Relevant papers published before 15 July 2025 were searched across four databases: Web of Science, PubMed, Science Direct, and Embase. A total of 28 papers which met the inclusion and exclusion criteria are included in this review. Results: Our findings indicate that LIFU reversed the depressive/anxious-like behaviors in the animal models and showed antidepressant/anti-anxiety effects among the state-of-art clinical studies. For example, immobility time in FST or TST is reduced in depressive animal models, and HRSD/BAI scales are improved in human studies. Key molecules such as BDNF/5-HT are found restored in animal models, and FC between key brain areas related to depression/anxiety is modulated after LIFU treatment. Notably, no brain tissue damage was observed in animal studies, and only mild adverse effects (such as dizziness and vomiting) were noted in a few human studies. Conclusions: The studies using LIFU to treat depression and anxiety remain in the preliminary stage. The mechanisms underlying LIFU’s mood effects—such as activation or inhibition of specific brain regions or neural circuits, anti-inflammatory effects, alterations in functional connectivity, synaptic plasticity, neurotransmitter levels, and BDNF—remain incompletely understood and warrant further investigation. Nevertheless, the LIFU technique holds promise for regulating both cortical and subcortical brain areas implicated in depression/anxiety disorders as a precise neuromodulation tool. Full article

The rapid increases in urbanization and time spent in built indoor environments have sparked significant concerns about their impact on human health and well-being. People who spend long hours in enclosed and highly artificial settings, such as hospital workers, are especially vulnerable to environmental stressors. This study examined whether applying biophilic (i.e., human tendency to connect with nature and other lifeforms) spatial design within hospital spaces could provide restorative benefits for nurses working in high-stress environments. Twenty-one nurses participated in this study, staying under two different conditions for 10 min: a control room with plain white walls and a biophilic space where the walls were entirely covered with vegetation. During the sessions, functional near-infrared spectroscopy was used to measure hemodynamic responses in the dorsolateral prefrontal cortex (DLPFC). Additionally, standardized self-report questionnaires were used to analyze the level of perceived restorativeness, affective states, mood, and anxiety. Results showed that exposure to the biophilic space significantly reduced oxyhemoglobin (oxy-Hb) concentrations in the DLPFC, reflecting relief from cognitive–emotional overload and enhanced neural stabilization. Psychological measures further indicated decreases in fatigue, depression, and anxiety, alongside increases in vigor, attentiveness, and perceived restorativeness in biophilic space. These findings demonstrate that even brief exposure to a biophilically designed indoor environment can produce neuropsychologically restorative effects, suggesting biophilic interventions as sustainable, effective strategies for healthier workplaces and urban environments. Full article

Objective: The objective was to evaluate the ability of Comprehensive Geriatric Assessment (CGA) parameters to predict all-cause mortality in older adults using both traditional statistical methods and machine learning (ML) approaches. Methods: A total of 1.974 older adults from a university hospital outpatient clinic were included in this study. Ninety-six CGA-related variables encompassing functional and nutritional status, frailty, mobility, cognition, mood, chronic conditions, and laboratory findings were assessed. Cox proportional hazards regression and six ML algorithms (logistic regression, support vector machine, decision tree, random forest, extreme gradient boosting, and artificial neural networks) were employed to identify mortality predictors. Model performance was evaluated using area under the curve (AUC), sensitivity, and F1-score. Results: During a median follow-up of 617 days (interquartile range [IQR]: 297–1015), 430 participants (21.7%) died. Lower Lawton instrumental activities of daily living scores, unintentional weight loss, slower gait speed, and elevated C-reactive protein levels were consistent mortality predictors across all models. The artificial neural network demonstrated the highest predictive performance (AUC = 0.970), followed by logistic regression (AUC = 0.851). SHapley Additive explanations (SHAP) analysis confirmed the relevance of these key features. Conclusions: CGA parameters provide robust prognostic information regarding mortality risk in older adults. Functional decline and inflammation markers offer greater predictive power than chronological age alone in assessing overall health and survival probability. Full article

In the breeding of farm animals, music serves as an environmental enrichment factor that can improve the mood and welfare level of animals. However, it is not clear whether pigs receiving different modes of musical stimulation can improve cognitive performance. This study aimed to explore the extent to which different music stimulation methods affect the cognitive ability-related behaviors and neural substances of weaned piglets by providing them with various music stimuli. Fifty-four piglets were randomly divided into three groups: control group (C Group), continuous music group (CM group), and intermittent music group (IM group). The CM group received half an hour of music stimulation in the morning and afternoon of each day when the piglets were active, the IM group was given a cross-stimulation mode between the music playing time and the music pause time, and the C group had a music player installed in the enclosure, but no music was played, and the test period was 3 d. The results of the study showed the following: (1) Compared with piglets in the C group, piglets in the CM and IM groups showed more exploring behavior and less aggressive behavior (p < 0.05), while the playing behavior of piglets in the CM and IM groups was significantly higher than those in the C group (p < 0.05). (2) Compared with the CM group, the expression of cognition-related DCX, BDNF, and EGR1 genes in hippocampal tissues of the IM group was significantly higher (p < 0.05), and the expression of CREB was significantly lower (p < 0.05). (3) Western blot results showed that the protein expression of neural tissue development and cognitive-related genes (DCX and BDNF) in the hippocampal tissues of the IM group was significantly higher (p < 0.05), and the protein expression of EGR1 was highly significant (p < 0.01), compared with the CM group. These findings may indicate that intermittent music patterns can improve the cognitive abilities of weaned piglets regarding the surrounding physical and social environmental cognitive abilities. Full article

The bone and brain, though distinct in structure and function, share remarkable physical, molecular, and developmental similarities. Emerging evidence reveals dynamic bidirectional crosstalk between these systems mediated by hormones, cytokines, extracellular vesicles (EVs), and neural signals. Bone-derived factors such as osteocalcin (OCN), lipocalin-2, and fibroblast growth factor (FGF) 23 influence cognitive functions, mood, and neurogenesis, while brain- and nerve-derived mediators, including leptin, serotonin, and sympathetic signals, modulate bone remodeling. Inflammation and aging disrupt this communication, contributing to cognitive decline, osteoporosis, and other age-related disorders. Stem cells and EVs have also been implicated as mediators in this axis, offering insights into regenerative strategies. Molecular signaling pathways and transcriptional regulators, such as Wnt/β-catenin, leptin, receptor activator of nuclear factor kappa-B ligand (RANKL), sclerostin (SOST), and nuclear factor kappa-B (NF-κB), play critical roles in maintaining bone–brain homeostasis. Additionally, shared biomarkers and pathological links between neurodegeneration and bone loss suggest new diagnostic and therapeutic opportunities. Studies support this inter-organ communication, yet further mechanistic and translational research is needed. This review highlights the molecular basis of bone–brain crosstalk, emphasizing inflammation, aging, and regulatory pathways, with a focus on future directions in biomarker discovery and therapeutic targeting. Understanding this crosstalk may help in early diagnosis and dual-targeted interventions for both bone and brain disorders. Full article