Search Results (13,222)

Background: Regional cerebral blood flow (rCBF) is a putative biomarker for neuropsychiatric disorders, including major depressive disorder (MDD). Methods: Here, we show that rCBF can be predicted from resting-state functional MRI (rsfMRI) at the voxel level while correcting for partial volume averaging (PVA) artifacts. Cortical patterns of MDD-related CBF differences decoded from rsfMRI using a PVA-corrected approach showed excellent agreement with CBF measured using single-photon emission computed tomography (SPECT) and arterial spin labeling (ASL). A support vector machine algorithm was trained to decode cortical voxel-wise CBF from temporal and power-spectral features of voxel-level rsfMRI time series while accounting for PVA. Three datasets, Amish Connectome Project (N = 300; 179 M/121 F, both rsfMRI and ASL data), UK Biobank (N = 8396; 3097 M/5319 F, rsfMRI data), and Amen Clinics Inc. datasets (N = 372: N = 183 M/189 F, SPECT data), were used. Results: PVA-corrected CBF values predicted from rsfMRI showed significant correlation with the whole-brain (r = 0.54, p = 2 × 10⁻⁵) and 31 out of 34 regional (r = 0.33 to 0.59, p < 1.1 × 10⁻³) rCBF measures from 3D ASL. PVA-corrected rCBF values showed significant regional deficits in the UKBB MDD group (Cohen’s d = −0.30 to −0.56, p < 10⁻²⁸), with the strongest effect sizes observed in the frontal and cingulate areas. The regional deficit pattern of MDD-related hypoperfusion showed excellent agreement with CBF deficits observed in the SPECT data (r = 0.74, p = 4.9 × 10⁻⁷). Consistent with previous findings, this new method suggests that perfusion signals can be predicted using voxel-wise rsfMRI signals. Conclusions: CBF values computed from widely available rsfMRI can be used to study the impact of neuropsychiatric disorders such as MDD on cerebral neurophysiology. Full article

Metastatic cancer, characterized by poor survival outcomes and grim prognosis, represents the final stage of malignancy. The current evidence regarding the prophylactic effects of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors on metastatic cancer remains largely unexamined. With a confirmatory approach based on the Cochrane recommendation, we conducted a frequentist-based network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating such medications. The primary outcome was the incidence of metastatic cancer, while secondary outcomes included safety profiles assessed through dropout rates. The findings were reaffirmed by sensitivity analysis with a Bayesian-based NMA. This NMA of 207,606 participants from 67 RCTs revealed that only efpeglenatide demonstrated a statistically significant reduction in metastatic cancer events compared to controls (odds ratio = 0.26, 95% confidence intervals = 0.09 to 0.70, p = 0.010, number needed to treat = 188.4). Efpeglenatide’s efficacy was not confined to specific cancer types. Safety profiles were comparable across all treatments. These findings indicate that efpeglenatide may possess a broad, systemic preventive effect against metastatic cancers, potentially operating through mechanisms that are not restricted to individual organ systems. Further research is warranted to elucidate the molecular pathways underlying its anti-metastatic properties and to explore its role in preventive oncology. Full article

Introduction: Osteoarthritis (OA) is a chronic degenerative joint disease with limited treatment options focused primarily on symptom management. Emerging evidence suggests that dietary interventions may influence inflammation and pain through modulation of the gut microbiome and metabolome. Methods: We conducted a 4-week open-label pilot trial evaluating the effects of an anti-inflammatory dietary intervention (ITIS diet) in 20 patients with knee OA (ClinicalTrials.gov ID: NCT05559463, registered prior to enrollment; sponsor: University of California, San Diego; responsible party: Monica Guma; study start date: 1 October 2021). The following were assessed before and after the intervention: (1) clinical outcomes; (2) gut and salivary microbiomes; and (3) salivary, stool, and plasma metabolomes. Responders were defined as patients achieving ≥30% reduction in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores. Results: The ITIS diet was well-tolerated, with good adherence (66.2%) and a significant improvement in clinical outcomes, including reduced pain and improved overall health measured with the visual analog scale (VAS). Responders (n = 8) showed distinct gut microbiome and metabolome profiles compared to non-responders (n = 12). Notably, taxa within the Lachnospiraceae family exhibited dynamic, bidirectional shifts post-intervention: Anaerostipes and Limivivens were enriched among responders and negatively correlated with pain scores, while Oliverpabstia and Fusicatenibacter were depleted following dietary intervention. These taxa also showed strong correlations with anti-inflammatory metabolites, including hydroxydecanoic acid derivatives and pyridoxine. Furthermore, subsequent network analysis revealed more structured and selective microbiome–metabolome interactions in responders, specifically post-intervention. Conclusions: This pilot study shows that a short-term anti-inflammatory dietary intervention was associated with meaningful changes in the gut microbiome and metabolome. Members of the Lachnospiraceae family emerged as key taxa associated with pain reduction and anti-inflammatory metabolite production. Our findings suggest that specific microbial responses—rather than global diversity changes—may underlie dietary responsiveness in OA. Although exploratory and limited by sample size, our results support further investigation into personalized, microbiome-informed nutritional strategies for OA management. Full article

Background/Objectives: No Arabic-language version of the Observable Social Cognition Rating Scale (OSCARS) is available that allows to properly and specifically assess social cognition (SC) in Arabic-speaking populations. This study aimed to examine the preliminary psychometric characteristics of the Arabic translated version of the OSCARS, including factor structure, reliability, concurrent validity, and measurement invariance across sex. Methods: This cross-sectional study has been conducted during February and March 2024 and included 113 chronic, remitted, and clinically stable patients with schizophrenia. Results: The originally proposed two-factor model (Social Cognitive Bias and Social Cognitive Ability) showed acceptable model fit after removal of two items that yielded low factor loadings (items 2 and 3). Total and factor scores showed good internal consistency, with Cronbach’s alpha of 0.85–0.94. Measurement invariance was established across sex groups at the configural, metric, and scalar levels. No significant differences emerged between male and female patients for latent mean scores of the OSCARS. Finally, concurrent validity was supported by appropriate patterns of correlations with functioning, recovery, and emotional intelligence measures. Conclusions: The Arabic OSCARS stands out as a brief, valid, reliable, and comprehensive assessment tool to evaluate SC in Arabic-speaking patients with schizophrenia based on the perspectives of interviewers. Offering this measure to clinicians and researchers who work in Arab settings may close the existing gap in the assessment of SC in schizophrenia. Due to its easy and fast application, the Arabic OSCARS is believed to be highly valuable in clinical and research practices. Full article

Background/Objectives: Human milk provides essential nutrients and immune factors with beneficial impact on term, but especially preterm infants’ development. Therefore, this study focuses on the quantification of differences in the peptidome composition of breast milk from mothers of preterm and term infants, keeping in mind that this could reflect different biological needs of these infants or indicate nutritional gaps for healthy development. Methods: In a prospective observational study, breast milk samples were collected from 10 mothers of preterm infants (29–36 weeks gestational age,) and 13 mothers of term infants (37–41 weeks) at day 4 to 6 postnatally. A non-targeted tandem mass spectrometry approach was employed to analyze the milk peptidome. Results: In total, 4570 peptides were quantified. Adjusting the results for maternal age, weight, and height revealed a significant difference for 130 peptides derived from 19 different proteins between preterm and term milk. Proteins comprised high abundant proteins (e.g., α_S1-casein, κ- casein, or ß-casein), but also proteins that are less prominent in milk but of high functional importance (e.g., Hypoxia-inducible factor 1-alpha, Olfactory receptor 4M1). The differentially abundant peptides included peptides derived from ß-casein, which have already been described as being involved in antimicrobial functions as well as proliferation stimulating. For another 32 peptides, bioactivity was predicted. Conclusions: The current study provides a comprehensive overview on the differences in the milk peptidome at different gestational ages independent from common maternal phenotypes and improved the database for future peptide functionality studies. Full article

Mild traumatic brain injury (mTBI) affects over 40 million people every year. One of its features includes the activation of microglia, the resident immune cells of the brain. Microglia assume different morphological states depending on their level of activation, such as surveilling ramified and activated hypertrophic, ameboid, and rod-like microglia. These states can be distinguished by multiple features, including the shape, span, and branching of microglia. Male Sprague–Dawley rats sustained mTBI using the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) (3 times, 1.5 J per impact) or sham treatment. Four days after the injury, brains were collected and stained for microglia using the ionized calcium-binding adapter molecule-1 (Iba-1) antibody. Cortical injury sites were identified in a subset of CHIMERA animals. Using the MicrogliaMorphology ImageJ plugin and the MicrogliaMorphologyR package, 27 morphological features were quantified from individual microglia, and k-means clustering was used to classify microglia as ramified, rod-like, ameboid, and hypertrophic states. The CHIMERA injury altered microglia morphology features, which contributed to increased hypertrophic (activated) and decreased ramified (inactive) microglia compared to the sham controls. Combined with the clinically relevant mTBI paradigm and semi-automated/unbiased approach, the current findings may contribute to microglia morphology classification. Full article

A greater understanding of health-promoting factors, such as hope, is crucial for preventing and enhancing the mental health of higher education students. The Herth Hope Index (HHI) is a 12-item tool that has been widely used to assess a comprehensive, non-temporal perception of hope. While this instrument has been used extensively in adult populations, most studies focus on clinical populations. Additionally, the HHI reveals inconsistencies in terms of scale dimensionality and items to be retained. Therefore, this study sought to assess the HHI’s psychometric characteristics in a sample of Portuguese Higher Education students. The person response validity, internal scale validity, unidimensionality, and uniform differential item functioning were assessed using a Rasch rating scale model. A total of 2227 higher education students participated during the e-survey activation period (spring semester of 2020). The mean age of the sample was 22.5 ± 6.2 years (range 18–59 years). Three of the twelve items (#3, #5, and #6) failed to satisfy the established criterion for goodness of fit. Following the elimination of these three items, the resultant nine-item scale exhibited satisfactory item fit to the model, appropriate unidimensionality (52.4% of the variance explained), enough person goodness of fit, sufficient separation, and the absence of differential item functioning. The 9-item version of the HHI had psychometric properties comparable to the original 12-item version. This study also underscores the importance of validated instruments for assessing hope-based interventions in academic contexts. Further research is necessary to explore the potential dimensions inherent to the hope concept and to identify variations in hope profiles among items influenced by cultural attributes. Full article

Background: Paroxysmal dyskinesias (PDs) are rare, episodic movement disorders characterized by sudden and involuntary hyperkinetic motor events. In paediatric populations, their diagnosis is often complicated by clinical overlap with epilepsy and other neurological conditions. Genetic underpinnings have increasingly been recognized as key to understanding phenotypic heterogeneity and guiding treatment. Objectives: This systematic review aims to provide a comprehensive overview of paediatric PD, with a focus on genetic aetiologies, clinical features, subtype classification, and therapeutic approaches, including genotype–treatment correlations. Methods: We systematically reviewed the literature from 2014 to 2025 using PubMed. Inclusion criteria targeted paediatric patients (aged 0–18 years) with documented paroxysmal hyperkinetic movements and genetically confirmed or clinically suggestive PD. Data were extracted regarding demographics, dyskinesia subtypes, age at onset, genetic findings, and treatment efficacy. Gene categories were classified as PD-specific or pleiotropic based on functional and clinical features. Results: We included 112 studies encompassing 605 paediatric patients. The most common subtype was Paroxistic Kinesigenic Dyskinesia (PKD). Male sex was more frequently reported. The mean onset age was 5.99 years. A genetic diagnosis was confirmed in 505 patients (83.5%), involving 38 different genes. Among these, PRRT2 was the most frequently implicated gene, followed by SLC2A1 and ADCY5. Chromosomal abnormalities affecting the 16p11.2 region were identified in ten patients, including deletions and duplications. Among the 504 patients with confirmed monogenic variants, 390 (77.4%) had mutations in PD-specific genes, while 122 (24.2%) carried pleiotropic variants. Antiseizure drugs—particularly sodium channel blockers such as carbamazepine and oxcarbazepine—were the most frequently reported treatment, with complete efficacy documented in 59.7% of the studies describing their use. Conclusions: Paediatric PDs exhibit significant clinical and genetic heterogeneity. While PRRT2 remains the most common genetic aetiology, emerging pleiotropic genes highlight the need for comprehensive diagnostic strategies. Sodium channel blockers are effective in a subset of genetically defined PD, particularly PRRT2-positive cases. Patients with pathogenic variants in other genes, such as ADCY5 and SLC2A1, may benefit from specific therapies that can potentially change their clinical course and prognosis. These findings support genotype-driven management approaches and underscore the importance of genetic testing in paediatric movement disorders. Full article

Background/Objectives—The personalisation agenda—matching the correct psychological therapy to diverse and comorbid mental disorders—is an unanswered dilemma in the worldwide literature which has far reaching consequences for public health. This hypothesis article addresses the question: can a biomedical approach resolve the personalisation agenda? Methods—Narrative review drawing on clinical psychology, translational psychiatry, and biomedical science literature. Results—Diverse attempts to resolve the personalisation agenda have not yet succeeded. Randomised controlled trials are uniquely biased due to unwanted placebo effects; network meta-analysis cannot address adequately which psychological therapy to use; new methodologies have not yet produced data; and neuroscientific analysis cannot yet explain how trauma-based therapies work. However, a biomedical model which divides psychological therapy into low, medium and high intensity interventions can resolve the personalisation agenda. Conclusions—Combining low intensity (placebo), with medium intensity (cognitive behavioural techniques) and high intensity interventions (trauma-based therapies) are theoretically synergistic if combined with psychosocial treatments/exercise, and used in sequence in the correct order. A biomedical model based on recent advances in placebo studies and neuroplasticity can resolve the personalisation agenda, and improve outcomes for mental disorder. Full article

Brain tumors elicit complex neuropsychiatric disturbances that frequently occur prior to radiological detection and hinder differentiation from major psychiatric disorders. These syndromes stem from tumor-dependent metabolic reprogramming, neuroimmune activation, neurotransmitter dysregulation, and large-scale circuit disruption. Dinucleotide hypermethylation (e.g., IDH-mutant gliomas), through the accumulation of 2-hydroxyglutarate (2-HG), execute broad DNA and histone hypermethylation, hypermethylating serotonergic and glutamatergic pathways, and contributing to a treatment-resistant cognitive-affective syndrome. High-grade gliomas promote glutamate excitotoxicity via system Xc⁻ transporter upregulation that contributes to cognitive and affective instability. Cytokine cascades induced by tumors (e.g., IL-6, TNF-α, IFN-γ) lead to the breakdown of the blood–brain barrier (BBB), which is thought to amplify neuroinflammatory processes similar to those seen in schizophrenia spectrum disorders and autoimmune encephalopathies. Frontal gliomas present with apathy and disinhibition, and temporal tumors lead to hallucinations, emotional lability, and episodic memory dysfunction. Tumor-associated neuropsychiatric dysfunction, despite increasing recognition, is underdiagnosed and commonly misdiagnosed. This paper seeks to consolidate the mechanistic understanding of these syndromes, drawing on perspectives from neuroimaging, molecular oncology, neuroimmunology, and computational psychiatry. Novel approaches, including lesion-network mapping, exosomal biomarkers or AI-based predictive modeling, have projected early detection and precision-targeted interventions. In the context of the limitations of conventional psychotropic treatments, mechanistically informed therapies, including neuromodulation, neuroimmune-based interventions, and metabolic reprogramming, are essential to improving psychiatric and oncological outcomes. Paraneoplastic neuropsychiatric syndromes are not due to a secondary effect, rather, they are manifestations integral to the biology of a tumor, so they require a new paradigm in both diagnosis and treatment. And defining their molecular and circuit-level underpinnings will propel the next frontier of precision psychiatry in neuro-oncology, cementing the understanding that psychiatric dysfunction is a core influencer of survival, resilience, and quality of life. Full article

Background/Objectives: Excessive intake of sugar-sweetened food (SSF) increases obesity risk. Various psychological, physiological, and environmental factors may drive high consumption of SSF. Due to blocking sweet tastes, the herb Gymnema sylvestre (GS) has been shown to reduce SSF consumption, but its impact on motivation to eat SSF is unknown. This research aimed to qualitatively investigate adults’ perceptions regarding effects of GS on their motivation to eat SSF when administered systematically (three times/day in-between meals, i.e., GS-SYS treatment) or ad libitum (up to six times/day at participants’ discretion, i.e., GS-ADLIB) over 14 days, compared to placebo (taste-matched mint; PLAC-SYS). Methods: This study represents the qualitative investigation of a placebo-controlled randomised cross-over trial, conducted as three 14-day phases. The qualitative investigation included interviews at baseline and three post-testing phases. Seven participants (mean age 34.7 ± 13.8 years; two males, five females) agreed to participate. Twenty-eight interviews (across phases) were thematically analysed using NVivo software, identifying themes and highlighting changes in motivation to eat SSFs across the study. Results: The GS-SYS and GS-ADLIB treatments made SSFs unpleasant to eat and increased mindful eating, subsequently increasing motivation to avoid SSFs. External factors could increase or decrease motivation, depending on individual circumstances. Participants preferred GS-SYS and GS-ADLIB over PLAC-SYS, feeling it was more effective at changing behaviours related to SSF intake. Self-control over SSF intake changed during the study, mostly due to external factors, and in part GS-ADLIB. Conclusions: Participants found both GS administrations successful as motivation to avoid SSF; GS-ADLIB was considered most effective. Full article

Background/Objectives: The transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism has been strongly associated with type 2 diabetes mellitus (T2DM) in various populations; however, its impact on different ethnic groups is not fully understood. Given the distinct minor allele frequency in Chinese populations, this study aimed to analyze the association of rs7903146 with the risk of T2DM in a Han Chinese cohort and its relationship with relevant clinical parameters. Methods: We conducted a case–control study including 600 patients with type 2 diabetes mellitus (T2DM) and 511 sex-matched non-diabetic controls of Han Chinese descent. The TCF7L2 rs7903146 (C/T) polymorphism was genotyped using a TaqMan™ SNP assay. Clinical parameters, including body mass index (BMI), fasting plasma glucose, hemoglobin A1c, lipid profile, and high-sensitivity C-reactive protein (hs-CRP), were compared between genotypes. Logistic regression analyses were performed under a dominant genetic model (CT/TT vs. CC), adjusting for age, sex, systolic and diastolic blood pressure, BMI, and smoking status. Subgroup analyses were conducted by sex, BMI category, age at diagnosis, and family history of T2DM. Given the exploratory nature of this study and the low frequency of the TT genotype, no formal correction for multiple testing was applied. Results: Frequencies of the CT and TT genotypes were higher in the diabetic group (p = 0.045) and were significantly associated with an increased risk of T2DM under a dominant genetic model (adjusted OR = 2.24, p = 0.025). Individuals with CT/TT genotypes had elevated fasting glucose and hs-CRP levels; these genotypes were also linked to higher BMI in the female T2DM patients. The T allele frequency varied across ethnic groups, being lowest in East Asians and highest in Latin (Brazilian/mixed ancestry) populations. Mechanistically, the T allele may contribute to T2DM via altered TCF7L2 expression, impaired insulin secretion, inflammation, and metabolic dysregulation. Conclusions: The TCF7L2 rs7903146 T allele was associated with an increased risk of T2DM and higher fasting glucose and hs-CRP levels in this Han Chinese cohort. The CT/TT genotypes were also associated with higher BMI in the female T2DM patients. While the findings are consistent with the known effects of this variant in other populations, mechanistic hypotheses such as the involvement of inflammatory or metabolic pathways remain hypothetical and warrant further functional validation. Full article

Recent advances in psychedelic research have renewed interest in their therapeutic potential for psychiatric disorders characterized by cognitive and behavioral rigidity. This review examines the rationale for using serotonergic psychedelics—particularly 5-HT₂A receptor agonists such as psilocybin—in the treatment of eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). The paper contextualizes these interventions within the broader serotonin hypothesis of EDs, emphasizing serotonergic dysregulation and impaired cognitive flexibility as central features of these conditions. Drawing from animal models, human neuroimaging studies, and emerging clinical trials, the authors outline how psychedelics may promote neuroplasticity and psychological insight through modulation of 5-HT₂A signaling. Preliminary evidence from open-label studies suggests psilocybin may improve ED symptoms and quality of life, though findings are early and methodologically limited. The paper also reviews data on ayahuasca, MDMA, and non-psychedelic serotonergic agents, highlighting both the promise and complexity of psychedelic-assisted therapy in EDs. The authors conclude that while further controlled trials are needed to clarify efficacy, safety, and optimal treatment parameters, psychedelics offer a novel, mechanistically distinct avenue for addressing entrenched ED psychopathology. Full article

Burnout, characterized by emotional exhaustion and depersonalization, is increasingly recognized as a significant mental health concern with psychiatric implications. This cross-sectional study explored variables associated with current burnout levels among 2004 teachers in 19 Latin American countries and Spain, drawing on retrospective perceptions of COVID-19 pandemic-related changes in work conditions and student behavior. Using a comprehensive survey, researchers gathered demographic information, work-related characteristics, and burnout levels measured by the Maslach Burnout Inventory. Participants were recruited through social media platforms and teacher groups. Participants reported high emotional exhaustion, with 45.9% exceeding the clinical threshold. Moderate depersonalization levels were observed, with 30.2% scoring above the clinical cutoff. Hierarchical regressions indicated that emotional exhaustion was significantly predicted by individual (e.g., gender, age, socioeconomic status, pre-existing mental and chronic illnesses), school (e.g., school level, sector, and workload), and student factors (e.g., behavior and social adjustment problems), accounting for 17.4% of the variance. Depersonalization was similarly associated with individual (e.g., gender, age, education, and pre-existing mental illness), school (e.g., workload and school level), and student characteristics (e.g., educational, behavioral, and family adjustment problems), explaining 6.5% of the variance. These findings contribute to psychiatric and psychological research by identifying specific risk profiles for chronic stress syndromes in educators—an occupational group facing long-term psychological impacts from the COVID-19 crisis. This study underscores the need for interdisciplinary psychiatric approaches to diagnose and prevent burnout and promote teacher well-being through clinical and policy-level interventions. Full article

Introduction: Globally, approximately 53 million children under the age of five live with some form of developmental disability. Exposure to heavy metals has been identified in the literature as a contributing factor in the etiology of neurodevelopmental disorders, however it usually is understudied. Even at low concentrations, these toxicants pose a risk to neurodevelopment, when affecting children early as in the prenatal period. This study aims to systematically review the literature on the associations between exposure to toxic heavy metals and neurodevelopmental outcomes in children. Method: The review was registered at the International Prospective Register of Systematic Review-PROSPERO, under number CRD420250653229 and searches were conducted in the PubMed, Scopus, Web of Science, EMBASE, Lilacs and PsycInfo databases. Results: A total of 68 articles were included, comprising 48 longitudinal studies and 20 cross-sectional studies, published between 2006 and 2025, with a combined sample of 215,195 individuals from 23 countries. Lead was the most consistently investigated metal, appearing in 75% of the studies, followed by mercury, cadmium, and arsenic. Most findings referred to prenatal exposure. Cognitive and motor outcomes were predominantly affected by exposure to Pb and Hg, while behavioral outcomes showed negative associations mainly with Pb and As. Conclusions: The majority of the studies analyzed indicated adverse effects resulting from exposure to heavy metals during pregnancy, especially in the early months, highlighting the vulnerability of the developing brain. Full article