Search Results (1,865)

Background: Language impairment is a core feature of Major Neurocognitive Disorder (MND), yet the domain-specific relationship between language functioning and everyday functional status remains insufficiently characterized. Methods: We conducted a retrospective observational study in 125 older adults diagnosed with MND according to DSM-5 criteria with mild-to-moderate cognitive impairment measured with Mini-Mental State Examination (MMSE). Language performance was assessed using semantic, phonemic verbal fluency and confrontation naming. Functional status was evaluated using basic (BADL) and instrumental activities of daily living (IADL). Ordinal logistic regression models examined associations between language domains and functional outcomes, adjusting for global cognitive status (MMSE), demographic variables, multimorbidity, and depressive symptoms. Model fit was evaluated using the Akaike Information Criterion. Results: Semantic fluency emerged as the best-performing predictor of BADL across all hierarchical models, remaining statistically significant after full adjustment for MMSE and clinical covariates (β ≈ 0.60, p < 0.05). Phonemic fluency showed the most robust association with IADL, with a stable effect across models, reaching a trend toward statistical significance in the fully adjusted analyses (β ≈ 0.22–0.27, p = 0.069). Naming ability did not influence functional outcomes. All observed associations persisted after controlling for MMSE, demographic variables, multimorbidity, and depressive symptoms. Conclusions: Language abilities showed differential associations across language domains with functional status in this sample of patients with MND. Semantic fluency was associated with basic self-care, while phonemic fluency showed a trend toward association with instrumental daily activities. These relationships remained observable after adjustment for global cognitive impairment, suggesting verbal fluency as a potentially sensitive marker of functional vulnerability. Full article

Fibromyalgia, a syndrome characterized by hyperalgesia and ‘negative emotionality’, and major depressive disorder (MDD) demonstrate substantial overlaps in clinical, neurobiological, and therapeutic domains. Currently, treatment options for fibromyalgia remain limited; however, the epidemiology of this syndrome continues to grow worldwide. The use of animal models is indispensable for developing new treatment strategies for fibromyalgia. Meanwhile, the choice of animal paradigms is limited. Here, we used the ultrasound exposure of emotional stress on CBA, BALB/c, and C57BL/6 mouse strains to model this condition and to identify new molecular targets of fibromyalgia treatment. We exposed young male mice of three common strains to a three-week ultrasound stress (US) comprising emotionally negative and neutral frequencies of 20–25 kHz and 25–45 kHz, resulting in the development of altered pain sensitivity and signs of ‘negative emotionality’. Specifically, mice were studied for timid-like/aggressive behaviors and the tail flick response. Serum levels of corticosterone, cortisol, β-Endorphin, and brain-derived neurotrophic factor (BDNF), as well as brain gene expression of interleukin-33 (Il-33), Bdnf, and its receptor Trkb were investigated. Among the stressed mouse strains, C57BL/6 mice displayed augmented pain sensitivity, allodynia, and suppressed dominant behavior, whereas CBA and BALB/c mice demonstrated opposing changes. Glucocorticoid levels were increased in all stressed groups. Stressed C57BL/6 mice showed downregulated gene and protein expression of functionally inter-related BDNF and IL-33 molecules in the hippocampus, amygdala, and striatum, significantly correlating with behavioral outcomes, as well as lowered blood levels of β-Endorphin and elevated cortisol concentrations. Altogether, our study identified the BDNF/IL-33 regulatory pathway as a molecular correlate of fibromyalgia, and the use of US-exposed young C57BL/6 mice as a potential model that recapitulates this syndrome. Full article

Undergraduate students often engage in nighttime activities and electronic device usage that may adversely affect sleep quality and academic performance; therefore, factors associated with sleep quality are important. The objective of this study was to investigate the prevalence and associated factors of poor sleep quality in undergraduate students. Four hundred and five undergraduate students participated in a cross-sectional study and had no history of psychological disorders or use of medications affecting sleep. Data was collected using the Pittsburgh Sleep Quality Index (PSQI), musculoskeletal discomfort questionnaire, electronic device usage questionnaire and Depression Anxiety Stress Scales (DASS-21). Multivariate logistic regression was employed to analyze the factors associated with poor sleep quality. Among the undergraduate students in this study, 65.93% reported having poor sleep quality. The factors associated with poor sleep quality were stress (OR, 1.03; 95% CI, 1.01–1.06) and musculoskeletal discomfort (OR, 1.92; 95% CI, 1.23–2.99) after controlling for other variables. Undergraduate students frequently experience poor sleep quality, with stress and musculoskeletal discomfort being major contributors. These findings highlight the importance of mental health support and stress management programs in improving sleep quality and overall well-being, as well as in preventing long-term detrimental consequences for undergraduate students’ mental health, physical health and academic performance. Full article

Introduction: Previous research has shown that L-carnosine (β-alanyl-L-histidine) can reduce cognitive decline and improve mental health outcomes, but an updated systematic review of the effects of carnosine alone or in combination with other supplemental nutrients or bioactive compounds on these interconnected outcomes is lacking. Methods: We searched multiple databases from 1 January 2006 to 30 June 2025 for clinical trials evaluating the effects of all forms of carnosine (e.g., L-carnosine, zinc–L-carnosine) alone or in combination with other supplements on cognition, brain structure and function, mood, depression, or quality of life (QOL) outcomes. The Cochrane Risk of Bias (ROB) 2.0 tool was used to assess the ROB in randomized controlled trials (RCTs). When data were sufficient, random-effects meta-analyses were conducted. Strength of evidence (SoE) across studies was rated using the GRADE approach. Results: A total of 13 distinct studies (12 RCTs; 1 single-arm trial) involving healthy adults and patients with psychiatric or neurocognitive disorders were included. Studies were also heterogeneous in carnosine supplement dosage and duration. Overall 58% of included RCTs were rated ‘some concerns’ for ROB. Ten RCTs evaluated cognitive function, seven RCTs and one single-arm trial assessed mood and depression, four RCTs measured QOL, and three RCTs examined brain structure and function. Results from five RCTs found no significant differences in the majority of the cognitive function measures between L-carnosine supplement and placebo, but random-effects meta-analysis of three RCTs from a single research team found that anserine/L-carnosine supplementation significantly improved WMS-LM2 scores (pooled net change = 1.70; 95% CI 0.19, 3.2; I² = 58.3%) but not WMS–Local Memory Immediate Recall (LM1) scores (pooled net change = 0.76; 95% CI −0.18, 1.71; I² = 8.5%). Additionally, meta-analysis results showed that L-carnosine combined with anserine or antioxidant supplementation significantly improved the MMSE score compared to placebo (pooled net change = 0.62; 95% CI 0.23, 1.01), with small statistical heterogeneity (I² = 21.3%). Most of the studies did not show significant effects in a wide range of mood and depression outcome measures or health-related QOL (data cannot be meta-analyzed). Conclusions: A low strength of evidence suggests that L-carnosine supplement combined with anserine or antioxidants can slow cognitive function decline among healthy elderly or patients with probable Alzheimer’s Disease or mild neurocognitive disorder. More high-quality RCTs are needed to verify these findings and to improve the certainty level of this body of evidence. Full article

Background and objectives: Intolerance of uncertainty (IU) is a well-established transdiagnostic process in anxiety (ANX) and major depressive disorder (MDD), and has been increasingly implicated in anorexia nervosa (AN). However, most previous research including patients with AN has relied on total or subscale scores from eating disorder measures, which obscures how specific eating attitudes and body dissatisfaction symptoms relate to distinct facets of IU. The primary objective of the present study was to characterize item-level networks linking eating attitudes, body dissatisfaction, and IU in a pooled clinical mental health sample, alongside a control group (CG). Methods: Data were drawn from a sample including individuals with symptoms related to AN (N = 105), MDD (N = 97), and ANX (N = 240), a comorbid group (N = 84) with symptoms of two or more of these conditions, and a CG (N = 842). Separate item-level networks were estimated for clinical and control groups, and network structure and centrality indices were compared. Results: Network analyses revealed distinct organizational patterns between the clinical and control subsamples. Although both networks showed identical diameters, the clinical network exhibited a shorter average path length and higher clustering, indicating stronger local connectivity, whereas the control network showed higher modularity. In the clinical subsample, nodes related to binge eating, post-eating guilt, and IU emerged as the most central and acted as key connectors between clusters. In contrast, the control network displayed a more distributed centrality pattern, suggesting a more integrated and homogeneous network organization. Conclusions: This study provides new evidence to refine our understanding of how IU relates to eating attitudes and body dissatisfaction across diagnostic mental health boundaries. Identifying highly influential psychopathological symptoms across eating, mood, and anxiety disorders, as well as bridge nodes linking these mental health domains, is important for understanding transdiagnostic symptom dynamics. These insights may inform the development of more sensitive screening and diagnostic tools, as well as targeted intervention points to support more personalized and mechanism-focused treatments. Full article

Background: Chronic stress is a major contributing factor to mood disorders, including depression and anxiety; however, the molecular mechanisms underlying individual differences in susceptibility to such disorders remain poorly understood. DNA methyltransferase 3a (Dnmt3a), a key epigenetic regulator, has been increasingly implicated in stress-related neurobiological adaptations. In this study, we employed a well-established mouse model of chronic social defeat stress (CSDS) to investigate the functional role of Dnmt3a in modulating individual susceptibility to social stress. Methods: Male C57BL/6J mice were exposed to chronic/submaximal social defeat stress (CSDS/SSDS). AAV vectors were used to achieve Dnmt3a overexpression or global and oligodendrocyte-specific knockdown in the nucleus accumbens (NAc). Behavioral tests, including social interaction, open field, and elevated zero maze, were conducted alongside Western blotting and immunofluorescence assays. Results: CSDS selectively increased Dnmt3a expression in NAc oligodendrocytes of stress-susceptible mice. Overexpression of Dnmt3a in the NAc enhanced susceptibility to stress, whereas its knockdown conferred resilience, without affecting baseline behaviors. Dnmt3a negatively regulated myelin basic protein (MBP) and dopamine D1 receptor expression. Stress-susceptible mice exhibited shortened myelinated segments and reduced D1 receptor levels, while D2 receptor expression remained unchanged. Conclusions: Dnmt3a in NAc oligodendrocytes modulates susceptibility to social stress through a Dnmt3a-MBP/D1 receptor-NAc pathway, highlighting a critical glia-neuron interaction. This mechanism extends our understanding of the neurobiological basis of stress-related disorders and positions Dnmt3a as a promising therapeutic target for developing precision interventions or biomarkers. Full article

Background/Objectives: Adolescent psychiatric inpatient units play a critical role in the management of severe psychiatric disorders and suicide risk. However, limited evidence exists regarding the clinical and familial factors that simultaneously influence suicidal ideation and treatment outcomes in hospitalized adolescents. This study aimed to identify demographic, diagnostic, and clinical predictors of suicidal ideation and clinical improvement among adolescents hospitalized in a tertiary child and adolescent psychiatry inpatient unit. Methods: This retrospective observational study included 75 adolescents aged 12–18 years who were hospitalized in a tertiary child and adolescent psychiatry inpatient unit between November 2023 and June 2025. Sociodemographic and clinical characteristics were obtained from medical records. Clinical improvement was evaluated using the Clinical Global Impression–Improvement (CGI-I) scale. Group comparisons were conducted using chi-square or Fisher’s exact tests for categorical variables and the Mann–Whitney U test for continuous variables. Multivariate logistic regression analyses were performed to determine independent predictors of suicidal ideation and clinical improvement. Results: Clinical improvement was evaluated in the full sample of adolescents (n = 75), and longer length of stay was independently associated with clinical improvement during hospitalization. Among adolescents admitted with suicidal ideation (n = 45), major depressive disorder, previous suicide attempt, irritability at admission, and fewer siblings were identified as independent predictors of suicidal ideation. In addition, female adolescents had higher rates of suicide attempts and non-suicidal self-injury, whereas psychotic disorders were more common among male adolescents. Conclusions: Suicidal ideation in hospitalized adolescents is strongly associated with affective pathology and prior suicidal behavior. Longer inpatient treatment duration appears to facilitate clinical improvement. These findings highlight the importance of early suicide risk stratification and adequate treatment duration in adolescent psychiatric inpatient care. Full article

Background/Objectives: Although clinically distinct, bipolar disorder (BP), schizophrenia (SZ), major depressive disorder (MDD), and social anxiety disorder (SAD) share fundamental biology. We mapped these transdiagnostic systemic mechanisms. Methods: Weighted Gene Co-Expression Network Analysis (WGCNA) of peripheral blood RNA-Seq datasets evaluated module preservation, hub gene disruption, and microRNA (miRNA) networks. Results: Seven modules showed robust cross-disease preservation. Overall, 56 of 105 candidate hub genes exhibited altered expression, with 22 passing the false discovery rate (FDR) correction. Hubs like IL1B, TLR2, and MMP9 dominated networks linked to altered inflammatory signaling and structural remodeling. Downregulated ribosomal hubs characterized systemic metabolic stress. Discussion: These signatures capture extensive systemic dysregulation. Inflammation and metabolic shifts correlate strongly with pathways regulating chronic neuroinflammation, epigenetic control, and dendritic pruning. Computational models suggest these cascades evade miRNA controls, potentially compromising structural neural plasticity. Conclusions: This shared transcriptomic architecture challenges rigid diagnostic boundaries. Identifying systemic immune dysregulation and translational alterations as core pathogenic denominators provides a rationale for transdiagnostic therapies targeting upstream systemic networks to mitigate neural vulnerabilities. Full article

Background/Objectives: Major depressive disorder (MDD) remains a leading cause of disability worldwide and exhibits substantial biological heterogeneity that is not adequately captured by current symptom-based diagnostic systems. While the classical monoamine hypothesis has historically guided antidepressant development, it does not fully account for variability in treatment response, delayed therapeutic onset, or the persistence of cognitive and anhedonic symptoms. Converging evidence from molecular, neuroimaging, and translational studies increasingly implicates glutamatergic dysregulation and impaired neuroplasticity as key mechanisms in depressive pathology. This narrative review aims to integrate monoaminergic and glutamatergic perspectives within a dimensional framework that may help explain clinical heterogeneity and inform mechanism-based treatment strategies. Methods: A narrative synthesis of the literature was conducted using major biomedical databases including PubMed, Scopus, and Web of Science. Preclinical studies, neuroimaging investigations, biomarker research, randomized clinical trials, and meta-analyses examining monoaminergic dysfunction, glutamatergic signaling, neuroplasticity pathways, and rapid-acting antidepressants were reviewed and thematically integrated. Results: Evidence indicates that depressive syndromes may reflect varying contributions of monoaminergic dysregulation and glutamatergic–neuroplastic impairment. Monoaminergic disturbances interact with inflammatory and neuroendocrine processes, including cytokine-driven activation of the kynurenine pathway. In parallel, alterations in glutamatergic signaling, glial function, and BDNF–TrkB–mTOR pathways contribute to synaptic atrophy and network dysfunction. Rapid-acting antidepressants such as ketamine, esketamine, and dextromethorphan–bupropion provide clinical proof-of-concept that direct engagement of synaptic plasticity mechanisms can accelerate symptom improvement, particularly in treatment-resistant depression. Conclusions: Integrating monoaminergic and glutamatergic mechanisms within a “monoamine–glutamate continuum” offers a conceptual framework for understanding depressive heterogeneity and treatment response. Multimodal approaches combining clinical phenotyping with inflammatory, neuroimaging, and molecular markers may ultimately support mechanism-informed precision psychiatry strategies in major depressive disorder. Full article

Background: Overweight and obesity remain major public health challenges in Puerto Rico, affecting over 70% of adults and contributing to cardiovascular, metabolic, and mental health disorders. This study explores the psychosocial and behavioral factors influencing obesity within low-income Puerto Rican communities, emphasizing both biological sex differences and socially defined sex-role influences, along with their respective mental health dimensions. Method: Using a qualitative approach, Community-Based Participatory Research (CBPR), ten focus groups were conducted with 71 participants (37 women and 34 men) from two municipalities in southern Puerto Rico. Discussions were analyzed thematically with the Socioecological and Health Belief Models to identify key determinants. Results: The data collected revealed that women expressed greater emotional vulnerability, frequently citing anxiety, depression, body image concerns, and stress-related eating as contributors to obesity. Men, meanwhile, reported frustration with diet adherence, economic limitations, and healthcare inaccessibility. Across participants, economic hardship, cultural norms, and limited health education emerged as major obstacles. Conclusions: Findings underscore the need for holistic, sex-informed and socially responsive interventions that integrate mental health support with nutritional and physical health strategies. Addressing self-esteem, emotional regulation, and stress management alongside behavioral modification can promote sustainable, culturally tailored obesity prevention in Puerto Rico. Full article

Major depressive disorder is a highly prevalent psychiatric disease, and many patients remain symptomatic despite treatment. Rodent models are central to preclinical depression research, but their translational impact is often constrained by the lack of direct human analogs. We conducted a review to identify behavioral tasks with direct cross-species analogs between rodents and humans. We focused on tests with comparable assay structures that measure depressive symptoms and related constructs. We followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and included all relevant studies. After screening 9680 studies and applying inclusion and exclusion criteria, 62 studies were included. We identified 10 behavioral tests with comparable human and rodent versions. These tests include assays of positive and negative valence systems, affective bias, and cognitive systems. These cross-species behavioral tests help close the gap between animal and human paradigms and advance the understanding of the neurobiology underlying depression. Each test has distinct strengths and limitations in its implementation across species. These assays offer a promising bridge between human and rodent research, and continued efforts to standardize and develop these tests will help maximize their utility in enhancing the understanding of depression and developing more effective treatments for mood disorders. Full article

Background and Objectives: Major Depressive Disorder (MDD) and Bipolar Disorder (BD) lack objective molecular stratification despite partial clinical overlap, particularly during depressive phases. This cross-sectional study explored whether coordinated peripheral biomarker patterns could be identified using an integrated multivariate analytical framework. Materials and Methods: A total of 151 participants (MDD n = 41; BD n = 40; HC (healthy controls) n = 70) were profiled for 42 blood-derived parameters including composite inflammatory indices, hematological markers, trace elements measured by ICP-MS, and circulating BDNF and NLRP3 quantified by ELISA. Data were analyzed using univariate testing, unsupervised dimensionality reduction (PCA, t-SNE), and supervised classification (PLS-DA with cross-validation and permutation testing). Results: Thirty-seven of 42 parameters showed significant inter-group differences (p < 0.05). Circulating NLRP3 concentrations were markedly reduced in both psychiatric groups compared with HC. Composite inflammatory indices (NLR, SIRI, SII) were elevated in MDD. Zinc levels were modestly reduced, while manganese levels were increased in psychiatric cohorts. BDNF showed lower concentrations in MDD and higher concentrations in BD relative to HC. Cross-validated PLS-DA classification for psychiatric disorder vs. controls yielded an accuracy of 89.4% (AUC-ROC 0.947), with permutation testing indicating performance above chance. However, the sample-to-variable ratio and exploratory design warrant cautious interpretation. Conclusions: Multidomain peripheral biomarker profiling identified coordinated biochemical differences across diagnostic groups. These findings suggest the presence of multidimensional peripheral signatures associated with mood disorders within an exploratory framework. Full article

Migraine is a highly prevalent and disabling neurovascular disorder that represents a major global health burden due to its significant impact on quality of life and socioeconomic costs. Increasing evidence suggests that migraine pathophysiology involves complex interactions between neuronal hyperexcitability, vascular dysregulation, oxidative stress, and neuroinflammatory processes. Oxidative and nitrosative stress are increasingly recognized as key contributors to migraine mechanisms, influencing mitochondrial dysfunction, cortical spreading depression, and trigeminovascular activation. Nitric oxide plays a central role in these processes by regulating vascular tone, nociceptive signaling, and neurogenic inflammation through downstream pathways such as the soluble guanylate cyclase–cyclic guanosine monophosphate (NO–sGC–cGMP) signaling cascade. Dysregulation of nitric oxide signaling and increased oxidative stress may contribute to endothelial dysfunction and impaired cerebrovascular regulation observed in migraine patients. In addition, accumulating evidence highlights the role of neuroinflammatory mechanisms, including microglial activation and cytokine-mediated signaling, which may amplify nociceptive transmission within trigeminal pathways. Migraine is increasingly recognized as a systemic disorder associated with several comorbid conditions, including Parkinson’s disease, fibromyalgia, and autoimmune diseases such as Sjögren’s syndrome. This review summarizes recent advances regarding the interactions between oxidative stress, nitric oxide signaling, endothelial dysfunction, and neuroinflammation in migraine and discusses their potential therapeutic implications. Full article

Dementia caregiving represents a major public health challenge, with spousal caregivers assuming the greatest burden. Spouses, themselves typically older adults, provide high intensity, long-term, and largely unpaid care across all stages of cognitive decline. Despite their central role in dementia care, the health consequences experienced by spousal caregivers remain insufficiently characterized in the literature and inadequately addressed in clinical and public health practice. This structured narrative review synthesizes current evidence on the multidimensional impact of dementia caregiving on the physical, psychological, cognitive, social, and financial health of spousal caregivers. It further contextualizes these consequences within the trajectory of dementia progression, and identifies interventions, support systems, and policy considerations necessary to mitigate caregiver burden. Spousal caregivers experience disproportionate burden due to continuous, escalating responsibilities that often mirror the progressive deterioration of their partners. Emotional burdens, including uncertainty during pre-diagnostic stages, role strain, conflict, loss of intimacy, and anticipatory grief. Physically, spouses endure musculoskeletal strain, sleep disruption, poor nutrition, and heightened frailty risk. Psychologically, spousal caregivers exhibit elevated rates of depression, anxiety, loneliness, and stress-related disorders. Socially, caregivers experience substantial isolation, stigma, and erosion of social networks. Financial hardship, including early retirement, reduced employment, and uncompensated care hours, further exacerbate stress. Evidence suggests that chronic caregiving stress contributes to biological changes such as immune dysregulation, inflammation, acceleration, aging, and potential cognitive decline in caregivers themselves. Caregiver burden influences patient outcomes as evidenced by increased emergency department use, falls, and earlier institutionalization in persons with dementia whose caregiver is subjected to a high burden. Current care models rarely include routine, caregiver assessment or structured guidance following diagnosis, resulting in substantial unmet needs. Effective mitigation requires integrated, stage-sensitive interventions, including psychosocial support, caregiver education, respite services, culturally tailored programs, and digital health tools, alongside broader policy reforms to reduce financial and structural barriers. Full article

Background: The prevalence of mental disorders, particularly anxiety and depression, has been increasing and is becoming a major public health concern in Portugal. Digital mental health solutions offer scalable and accessible tools for monitoring and managing mental health. ‘P5 Mental Health’ has been created as a platform to assess and monitor symptoms of anxiety and depression in the Portuguese population, and to offer strategies to promote well-being to support users. Objective: This study aims to (1) describe the P5 Mental Health platform, (2) evaluate its feasibility as a digital mental health monitoring tool, and (3) analyze trends in the prevalence and severity of anxiety and depression symptoms over a four-year period, particularly in response to major societal stressors. Methods: Between September 2020 and September 2024, 46,032 responses were collected from platform users. Anxiety and depression symptoms were assessed using the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scales. Longitudinal trends were analyzed across four time periods. Welch’s ANOVA and Games–Howell post hoc tests were conducted to compare symptom severity across time, and ordinal logistic regression was used to examine the impact of time on symptom progression. Results: Anxiety and depression symptoms increased between 2020 and 2022, stabilized thereafter, and showed a slight decline in 2024. The proportion of users reporting moderate to severe anxiety (GAD-7 ≥ 10) rose from 30.87% in September 2020 to 66.30% in June 2022. Similarly, the prevalence of moderate to severe depressive symptoms (PHQ-9 ≥ 10) rose from 3.62% in March 2021 to 51.54% in August 2021. Despite a small decrease in 2024, symptom levels remained significantly higher than baseline levels recorded at the beginning (p < 0.001). A strong positive correlation was found between anxiety and depression symptoms (r = 0.739, p < 0.001), underscoring their high comorbidity. Conclusions: This study demonstrates the feasibility of the P5 Mental Health platform as a real-time mental health monitoring tool, particularly during periods of heightened social and economic stress. The findings highlight the need for sustained digital mental health interventions beyond crisis periods to ensure long-term engagement; however, future improvements should focus on increasing user engagement and adding personalized features to ensure long-term mental health management. Full article