Search Results (156)

Background: Fibromyalgia (FM) is a chronic condition characterized by widespread pain, fatigue, cognitive difficulties, and psychological symptoms. Patients often present distinct personality traits and psychopathological patterns associated with symptom severity. Objective: To examine psychopathological profiles in FM patients based on functional, physical–somatic, and emotional impairment domains, as well as on cumulative disease severity. Materials and Methods: A cross-sectional study was conducted with 70 women clinically diagnosed with FM at a specialized Fibromyalgia Unit. Psychological functioning was assessed using the Personality Assessment Inventory, and disease impact was measured with the Fibromyalgia Impact Questionnaire. Hierarchical cluster analyses were used to classify participants into mild and severe clusters across FIQ domains, and psychological profiles were compared. Results: Patients with severe functional impairment had more affective dysregulation (76.43 vs. 70.20, p < 0.01) and somatic complaints (85.57 vs. 79.76, p < 0.05) than those with mild impairment. The severe–physical cluster showed greater mood instability, somatization, and suicidal ideation (60.94 vs. 53.61, p < 0.05). The severe–emotional cluster had higher rates of major depression (85.71% vs. 64.28%) and persistent depressive disorder (76.19% vs. 70.61%, p < 0.05). Severe showed more emotional instability and somatization, distinguishing it from mild. Greater cumulative severity intensified depressive and somatic disorders. Discussion: Findings support FM’s biopsychosocial profile, where emotional distress may relate to psychological and physical symptoms, reinforcing the need for personalized, multidisciplinary care and comprehensive assessment. Full article

Background: Depression is a mental disorder characterized by a combination of somatic and cognitive disturbances, in which a predominantly sad or irritable mood significantly interferes with the patient’s functioning. This condition can affect individuals of all ages and socioeconomic backgrounds. Currently, various studies are exploring a possible association between oral dysbiosis and depression—an increasingly relevant topic, as confirmation of such a relationship could position the oral microbiota as a potential etiological or diagnostic factor for depression, given its accessibility and ease of analysis. Aim: To present a qualitative synthesis of studies addressing how oral dysbiosis influences the onset of depression, as well as the importance of controlling this alteration of the oral microbiota to aid in the prevention of the disease. Materials and Methods: The PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) outline the procedures to be followed for conducting this systematic review. The article search was carried out on 22 May 2025, across the PubMed, Scopus, Scielo, and The Cochrane Library databases, using terms related to “depression” and “oral dysbiosis”. Studies published within the last 10 years that addressed the potential association between oral dysbiosis, and depression were included. Furthermore, the quality of the studies was assessed using various tools depending on their design: the Newcastle–Ottawa Scale (NOS) was applied to case-control and cohort studies; the Joanna Briggs Institute (JBI) critical appraisal checklist was used for cross-sectional studies; and experimental studies were evaluated using SYRCLE’s Risk of Bias Tool. Results: A total of eleven studies were included in this systematic review. The findings suggest the presence of alterations in the oral microbiota of patients with depression, particularly in terms of composition, structure, and diversity. A reduction in alpha diversity—an indicator of local microbial balance—was observed, along with an increase in beta diversity, indicating greater inter-individual variability, which may be associated with inflammatory processes or immunological dysfunctions. Some studies reported differing results, which may be attributable to methodological variability regarding study design, or the populations sampled. Conclusions: This systematic review suggests that the oral microbiome could be considered a diagnostic biomarker and therapeutic target for depression, as the analyzed studies demonstrate a significant association between oral microbiome dysbiosis and this mental disorder. However, the methodological heterogeneity among the studies highlights the need for further research to confirm this potential relationship. Full article

Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, often arising in the absence of structural brain damage. Yet, both conditions exhibit considerable clinical overlap—particularly in the domains of cognitive dysfunction, emotional dysregulation, and symptom persistence despite negative investigations. Objective: This review critically examines the shared and divergent features of PCS and FND/FCD. We explore their respective epidemiology, diagnostic criteria, and risk factors—including personality traits and trauma exposure—as well as emerging insights from neuroimaging and biomarkers. We propose the “Functional Overlay Model” as a clinical tool for navigating diagnostic ambiguity in patients with persistent post-injury symptoms. Results: PCS and FND/FCD frequently share features such as subjective cognitive complaints, fatigue, anxiety, and heightened somatic vigilance. High neuroticism, maladaptive coping, prior psychiatric history, and trauma exposure emerge as common risk factors. Neuroimaging studies show persistent network dysfunction in both PCS and FND, with overlapping disruption in fronto-limbic and default mode systems. The Functional Overlay Model helps to identify cases where functional symptomatology coexists with or replaces an initial organic insult—particularly in patients with incongruent symptoms and normal objective testing. Conclusions: PCS and FND/FCD should be conceptualized along a continuum of brain dysfunction, shaped by injury, psychology, and contextual factors. Early recognition of functional overlays and stratified psychological interventions may improve outcomes for patients with persistent, medically unexplained symptoms after head trauma. This review introduces the Functional Overlay Model as a novel framework to enhance diagnostic clarity and therapeutic planning in patients presenting with persistent post-injury symptoms. Full article

Background: Between 40 and 70% of the population with autism have been found to suffer from functional gastrointestinal disorders (FGIDs). The emergence of FGIDs is related to lower quality of life and greater medical resources, somatization and emotional instability. There is a paucity of research available that examines gastrointestinal symptoms and sensory responses in individuals with autism in different countries and cultures. The aim of the present study is to compare the possible differences between gastrointestinal symptoms and sensory reactivity between two samples of individuals with autism from Spain and Colombia. Methods. Differences in gastrointestinal symptoms and sensory response were analysed between individuals with autism from Spain (n = 65; mean age = 8.91, SD = 4.02) and Colombia (n = 62; mean age = 10.16, SD = 5.31). Results. No differences were found as a function of age, sex and autism severity between Spanish and Colombian participants. More severe functional nausea and vomiting was reported by the Colombian sample when compared with the Spanish sample (p < 0.00, d = 0.42). Similarly, greater sensory reactivity emerged in Colombian individuals with autism relative to Spanish individuals with autism. Conclusions. Due to methodological limitations, sample size and other factors that could not be analysed in this research, it is not possible to draw conclusions about the influences of cultural or biological factors on gastrointestinal symptomatology and sensory reactivity among both autistic populations. This work could encourage more rigorous cross-cultural research in the future. Full article

DNA-deaminase AID plays a pivotal role in adaptive immunity, antibody diversification and epigenetic regulation. AID catalyzes cytidine deamination in immunoglobulin genes, facilitating somatic hypermutation (SHM), class-switch recombination (CSR) and gene conversion (GC). However, the dysregulation of AID activity can lead to oncogenic mutations and immune disorders such as hyper-IgM syndrome type 2 (HIGM2). At present the number of studies investigating the role of AID polymorphic variants in the promotion of pathology is low. The current review examines the structural and functional aspects of AID, focusing on the impact of amino acid substitutions—both natural polymorphisms and artificial mutations—on its catalytic activity, substrate binding and interactions with regulatory proteins. Additionally, a bioinformatic analysis of single-nucleotide polymorphisms of AID deposited in the dbSNP database was performed. SNPs leading to amino acid substitutions in the primary protein structure were analyzed. The bioinformatic analysis of SNPs in the AID gene predicts that among 208 SNPs causing amino acid substitutions in the primary protein structure, 62 substitutions may have significant negative impact on the functioning of AID. The integration of computational predictions with experimental data underscores the importance of AID regulation in maintaining immune homeostasis and highlights potential markers for immune-related pathologies. This comprehensive analysis provides insights into the molecular mechanisms of AID dysfunction and its implications for disease. Full article

Background: Even with advanced management involving pharmacologic and ventilatory strategies, respiratory dysfunction increases morbidity and reduces the quality of life. This narrative review examines how craniofacial and cervical manipulative interventions—including nasomaxillary skeletal expansion, breathing re-education, and structural techniques—may holistically optimize airway function by enhancing neurological and lymphatic dynamics, modulating vagal tone, reducing pharyngeal collapsibility, and supporting immune regulation across diverse clinical settings. Objectives: To explore manual techniques that influence respiratory and autonomic function and to evaluate their reported clinical efficacy and supporting evidence, particularly in the context of airway disorders such as asthma and pneumonia. Methods: A narrative review of the literature from PubMed and Google Scholar was conducted using search terms related to airway function and osteopathic manipulative techniques (OMTs). The inclusion criteria spanned 2010–2025 English-language peer-reviewed full-text articles on airway function, OMT, and emergency airway maneuvers. Clinical trials, observational studies, and reviews were included; non-peer-reviewed content and animal studies (unless mechanistically relevant) were excluded. Chapman’s reflexes related to respiratory function were incorporated to highlight somatic–visceral correlations. Key Findings: The techniques reviewed included frontal lift, vomer manipulation, maxillary and zygomatic balancing, and cervical adjustments. Thoracic OMT methods, such as diaphragm doming and lymphatic pump techniques, were also addressed. Emergency techniques, such as the BURP and Larson maneuvers, prone positioning, and high-frequency chest wall oscillation, were presented as comparative strategies to OMTs for acute airway management. Conclusions: Craniofacial and cervical manipulations can be a promising adjunct for enhancing airway function. However, the current literature displays heterogeneity and lack of large-scale randomized trials, which emphasize the necessity for standardized research and the establishment of clinical guidelines with the collected evidence. Full article

Background/Objectives: Temporomandibular disorders (TMDs) are the most common cause of non-dental pain in the orofacial region. Due to the complex and multifactorial nature of TMD, a multidisciplinary approach is often required. The objective of this narrative review is to evaluate the effectiveness of multimodal therapies in the management of TMD. Methods: A literature search was performed using a combination of keywords: “TMD”, “TMJ”, “disorders”, “manual therapy”, “physical therapy”, “dry needling”, “botulinum toxin”, “Botox”, “splint”, and “psychotherapy”. The search was conducted in the PubMed, Google Scholar, and Scopus databases, focusing on studies involving human subjects. Results: The included studies reported that the use of multimodal approaches—such as physiotherapy, botulinum toxin injections, occlusal splints, and/or psychotherapy—led to symptom improvement or complete resolution in patients with TMD. Conclusions: Temporomandibular disorders are complex conditions with a multifactorial etiology involving both somatic and psychological components. Given the wide range of symptoms and the functional connections of the temporomandibular joint with the nervous, muscular, and skeletal systems—including the cervical spine—effective treatment of TMD requires a multidisciplinary strategy. Full article

GRIN2A has previously been identified as frequently mutated in tumor samples, leading to a hypothesized involvement of GRIN2A in tumorigenesis. Pathogenic GRIN2A germline variants, on the other hand lead, to neurodevelopmental disorders, with no evidence for tumor burden. Thus, we aimed for an independent assessment of somatic and germline variation in GRIN2A, hypothesizing that a distinct distribution of somatic variation indicates a tumorigenic effect. All publicly available GRIN2A variants were obtained from ClinVar, gnomAD and Cosmic to account for germline variation in affected individuals and the general population, as well as somatic variation. Functional consequences, mutational hotspots and gene expression were assessed for each dataset to draw conclusions on the potential pathomechanisms of tumorigenesis. Pathogenic germline variants in GRIN2A expose a clear genotype–phenotype association and are predominantly present in functionally relevant domains, while somatic GRIN2A variants exhibit a uniform distribution and no high abundance in functionally relevant domains. The expression of GRIN2A is lower in tumor samples compared to in non-diseased tissues. Given the non-uniform distribution and domain clustering, our results suggest that specific domains of GRIN2A are highly intolerant towards germline variation, while a lack of somatic mutational clustering and functional relevance refutes the previously hypothesized major role of GRIN2A in tumorigenesis. Full article

Serotonin (5-HT) is a neurotransmitter that also plays an important role in the regulation of vascular tone and angiogenesis. This review focuses on the involvement of the 5-HT system in pathological processes leading to the development of Alzheimer’s disease (AD). There is evidence that damage or dysfunction of the 5-HT system contributes to the development of AD, and different subtypes of 5-HT receptors are a potential target for the treatment of AD. A link has been established between AD, depression, stress, and 5-HT deficiency in the brain. There are new data on the role of circadian rhythms in modulating stress, depression, and the 5-HT system; amyloid β (Aβ) plaque clearance; and AD progression. Circadian disruption inhibits Aβ plaque clearance and modulates AD progression. The properties and functions of 5-HT, its receptors, and serotonergic neurons are presented. Special attention is paid to the central role of 5-HT in brain development, including neurite outgrowth, regulation of somatic morphology, motility, synaptogenesis, control of dendritic spine shape and density, neuronal plasticity determining its role in network regeneration, and changes in innervation after brain damage. The results of different studies indicate that the interaction of amyloid β oligomers (AβO) with mitochondria is a sufficient trigger for AD-related neurodegeneration. The action of 5-HT leads to an improvement in mitochondrial quality and the restoration of brain areas after traumatic brain injury, chronic stress, or developmental disorders in AD. The role of a healthy lifestyle and drugs acting on serotonin receptors in the prevention and treatment of AD is discussed. Full article

Background: Toxic oil syndrome (TOS) was a major food-borne epidemic that occurred in Spain in May 1981, caused by the ingestion of rapeseed oil adulterated with aniline. While the somatic sequelae of TOS have been well documented, its long-term cognitive consequences remain poorly understood more than four decades after exposure. Methods: In this case-control study, 50 individuals with clinically confirmed TOS were compared to 50 healthy controls matched for age, sex, and education. All participants completed a comprehensive neuropsychological assessment, along with questionnaires evaluating fatigue, anxiety, depression, and health-related quality of life. Multivariate regression models were adjusted for demographic and vascular risk factors, as well as for mood symptoms, fatigue, and use of central nervous system-acting medications. Structural equation modeling was used to explore the potential mediating effects of affective and fatigue symptoms on cognitive performance. Results: TOS survivors showed significantly poorer performance than controls in attention, executive function, processing speed, and global cognition after adjusting for demographic and vascular risk factors. However, these differences were no longer statistically significant after additional adjustment for fatigue, depression, anxiety, and central nervous system-acting medications. Structural equation modeling analyses revealed that affective symptoms—particularly fatigue—substantially mediated the relationship between TOS and cognitive performance. Conclusions: The cognitive profile observed mirrors that of disorders characterized by subcortical dysfunction and impaired neural connectivity, such as multiple sclerosis and vascular cognitive impairment. Although early postmortem studies in TOS did not demonstrate overt white matter lesions, our findings raise the possibility of long-lasting alterations involving both white and gray matter networks. These results emphasize the need to consider mood and fatigue symptoms when evaluating cognition in TOS survivors and point to the potential for widespread, enduring neurobiological effects stemming from the original toxic exposure. Full article

Background: Adjustment to stress requires the involvement of coping strategies. Using maladaptive coping strategies may precipitate the onset or recurrence of psychiatric disorders. On the other hand, the illness itself may alter the coping mechanisms of an individual. This study aims to identify the coping strategies in patients with bipolar disorder (BD) and major depressive disorder (MDD) and determine the correlation between coping strategies and clusters of psychiatric symptoms. Material and Methods: Socio-demographic and clinical data were analyzed for 30 inpatients with BD and 30 inpatients with MDD. The SCL-90 questionnaire and COPE inventory were filled in by the participants. Results: Compared to the general population, the patients with BD had lower scores for functional coping strategies and higher scores for one dysfunctional coping strategy. The patients with MDD had lower scores for all active functional and two passive functional coping strategies. By contrast, they presented higher scores on one passive functional and one dysfunctional coping strategy. Positive reinterpretation and growth were negatively correlated with somatization, depression, anxiety, interpersonal sensitivity, hostility, and psychoticism. Behavioral disengagement was positively correlated with depression, anxiety, somatization, interpersonal sensitivity, and psychoticism. Substance use was positively correlated with the number of episodes. Distinct coping mechanisms were associated with certain symptom clusters. Conclusions: Although dysfunctional coping strategies may predispose to psychiatric disorders, in our study, they appear to be state-dependent rather than trait-dependent. Full article

Background: An increased risk of cognitive decline has been reported in patients with older age bipolar disorder (OABD); however, the underlying factors contributing to this association remain unclear. This cross-sectional study aims to identify the clinical features associated with cognitive impairment in OABD. Methods: A total of 152 participants, aged at least 50 years and diagnosed with bipolar disorder (BD) and related disorders in agreement with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria, were included in the study and divided into two subgroups based on the presence/absence of cognitive impairment, defined as a diagnosis of Mild Neurocognitive Disorder or Major Neurocognitive Disorder. Univariate comparisons and multivariate logistic regression models were performed to investigate the associations between clinical variables and cognitive impairment. Results: Cognitively impaired patients had a higher prevalence of otherwise specified BD/cyclothymic disorder, while BD type 2 was more common in the cognitively unimpaired group. Additionally, the cognitively impaired group had a later onset of major mood episodes (p < 0.05), fewer lifetime depressive episodes (p = 0.006), a higher prevalence of vascular leukoencephalopathy (p = 0.022) and dyslipidemia (p = 0.043), a lower prevalence of agoraphobia (p = 0.040), worse global functioning (p < 0.001), and higher psychopathology severity (p < 0.001). Late onset, vascular leukoencephalopathy, and dyslipidemia were all independently associated with cognitive impairment. Conclusions: Atypical BD, late onset of mood episodes, and somatic comorbidities like vascular leukoencephalopathy and dyslipidemia are associated with a higher risk of developing cognitive impairment and neurodegenerative disorders in OABD patients. Full article

While whole-genome sequencing (WGS) using short-read technology has become a standard diagnostic test, this technology has limitations in analyzing certain genomic regions, particularly short tandem repeats (STRs). These repetitive sequences are associated with over 50 diseases, primarily affecting neurological function, including Huntington disease, frontotemporal dementia, and Friedreich’s ataxia. We analyzed 2689 cases with movement disorders and dementia-related phenotypes processed at Variantyx in 2023–2024 using a two-tiered approach, with an initial short-read WGS followed by ONT long-read sequencing (when necessary) for variant characterization. Of the 2038 cases (75.8%) with clinically relevant genetic variants, 327 (16.0%) required additional long-read analysis. STR variants were reported in 338 cases (16.6% of positive cases), with approximately half requiring long-read sequencing for definitive classification. The combined approach enabled the precise determination of repeat length, composition, somatic mosaicism, and methylation status. Notable advantages included the detection of complex repeat structures in several genes such as RFC1, FGF14, and FXN, where long-read sequencing allowed to determine somatic repeat unit variations and accurate allele phasing. Further studies are needed to establish technology-specific guidelines for the standardized interpretation of long-read sequencing data for the clinical diagnostics of repeat expansion disorders. Full article

Depression remains one of the most widespread and costly mental disorders, with the current first-line treatment efficacy of about a third, possibly due to its heterogeneous nature. Consequently, there is a need to identify reliable biomarkers for specific subtypes of depression, particularly neurological signatures that may help with targeted treatments. This study aimed to explore the connectivity between two important networks in the brain: the dorsal and ventral attention networks and the salience network, to determine their potential as biomarkers of depression subtypes. From resting electroencephalogram (EEG) data collected on 54 males and 46 females aged between 18 and 75 yr (M = 33 yr), functional network connectivity data were examined for their relationships with four depression subtypes. Beta and gamma wave connectivity was significantly associated with Anhedonia and Cognitive depression subtypes across and within all three networks while no significant results were found for alpha wave activity connectivity, and only one result was found for either the Mood or Somatic depression subtypes. In conclusion, these results provide further support for the concept of depression as heterogeneous rather than homogeneous and identify the novel neurophysiological signatures of two depression subtypes. Full article

Huntington’s disease (HD) is an inherited neurodegenerative disease characterized by uncontrolled movements, emotional disturbances, and progressive cognitive impairment. It is estimated to affect 4.3 to 10.6 per 100,000 people worldwide, and the mean prevalence rate among all published studies, reviews, and genetic HD registries is 5.7 per 100,000. A key feature of HD is the loss of striatal neurons and cortical atrophy. Although there is no cure at present, the discovery of the gene causing HD has brought us into a new DNA era and therapeutic advances for several neurological disorders. PubMed was systematically searched using three search strings: ‘“Huntington disease” + “stem cell”’, ‘”Huntington disease” + Mesenchymal stromal cell’, and ‘”Huntington disease” + “induced pluripotent stem cell”’. For each string, the search results were categorized based on cell type, and papers that included a clinical analysis were categorized as well. The data were extracted up to 2024. We did not include other databases in our search to have a comparable and systematic review of the literature on the topic. The collected data were analyzed and used for critical interpretation in the present review. Data are presented chronologically as clinical studies were published. Therapeutic strategies based on stem cells have drawn a lot of interest as possible HD therapies. Recent research indicates that NSCs have been the most often utilized stem cell type for treating HD. NSCs have been generated and extracted from a variety of sources, including HD patients’ somatic cells and the brain itself. There is strong evidence supporting the transplantation of stem cells or their derivatives in HD animal models, even if stem-cell-based preclinical and clinical trials are still in their early stages. Current treatment only aims at relieving the symptoms rather than treating the pathogenesis of the disease. Although preclinical trials in HD models have shown promise in improving cognitive and motor functions, stem cell therapy still faces many challenges and disadvantages including immunosuppression and immunorejection as well as ethical, technical, and safety concerns. Further research is required for a definitive conclusion. Full article