Search Results (140)

Motor deficits, including atypical gait, are common in individuals with autism spectrum disorder (ASD), although the precise nature and cause of this co-occurrence is unclear. Because walking is a natural activity and gait timing is a metric that is relatively accessible to measurement, we explored whether autistic gait could be described solely in terms of the timing of gait parameters. The aim was to establish whether temporal analysis, including machine learning models, could be used as a group classifier between ASD and typically developing (TD) individuals. Thus, we performed a high-resolution temporal analysis of gait on two age-matched groups of male participants: one group with high-functioning ASD and a comparison TD group (each N = 16, age range 7 to 35 years). The primary data were collected using a VICON^® 3D motion analysis system. Significant increased temporal variability of all gait parameters tested was observed for the ASD group compared to the TD group (p < 0.001). Further machine learning analysis showed that the temporal variability of gait could be used as a group classifier for ASD. Of the twelve models tested, the best-fitting model type was random forest. The temporal analysis of gait with machine learning algorithms may be useful as a future ASD diagnostic aid. Full article

Background/Objectives: Schizophrenia Spectrum Disorders (SSDs) carry a debilitating burden of disease which, even after pharmacological and psychological treatment are optimized, remains difficult to fully target. New online-delivered and user-led interventions may provide an appropriate, cost-effective answer to this problem. This study aims to retrieve the currently gathered findings on the efficacy of these interventions across several outcomes, such as symptom severity, social cognition, functioning and others. Methods: A systematic review of the current available literature was conducted. Of 29 potentially relevant articles, 26 were included and assigned at least one of four intervention types: Web-Based Therapy (WBT), Web-Based Psycho-Education (WBP), Online Peer Support (OPS) and Prompt-Based Intervention (PBI). Results: The findings were grouped based on outcome. Of 24 studies evaluating the effects of symptom severity, 14 have achieved statistically significant results, and 10 have not. WBT (such as online-delivered Cognitive Behavioral Therapy, Acceptance and Commitment Therapy, social cognition training and Mindfulness Training) seemed to be the most effective at targeting symptoms. Of 14 studies evaluating functioning, seven achieved significant results, four involving a form of social or neurocognitive training, suggesting a potential pathway towards functional improvements through interventions targeting cognition and motivation. Regarding social cognition, all seven studies measuring the effects of an intervention on this outcome produced significant results, indicating that this outcome lends itself well to remote, online administration. This may be linked with the nature of social cognition exercises, as they are commonly administered through a digital medium (such as pictures, videos and auditory exercises), a delivery method that suits the online-user led model very well. Conclusions: Online user-led interventions show promise as a new way to tackle functional deficits in SSD patients and achieve these improvements through targeting social cognition, a hard-to-reach component of the burden of SSDs which seems to be successfully targetable in a remote, user-led fashion. Symptomatic improvements can also be achievable, through the combination of these interventions with treatment as usual. Full article

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition in children that typically involves challenges in cognition, behavior, and communication. While many children with ASD exhibit significant impairments in both verbal and non-verbal communication, the severity and nature of these difficulties can vary widely. In addition to its impact on overall health, ASD also affects oral health, leading to increased vulnerability to dental disease. Aim: This narrative review aims to summarize key oral health challenges and care strategies for children with ASD, focusing on clinical risks, behavioral barriers, caregiver roles, and effective interventions. Materials and Methods: A comprehensive literature search was conducted using four databases—PubMed, Scopus, Web of Science, and Google Scholar—as well as relevant study registries where applicable. Peer-reviewed articles published in English between 2010 and 2024 were identified using keywords and their synonyms, such as autism spectrum disorder, children, oral care, dental practitioners, and parents. Studies were included based on relevance to oral health challenges and interventions in children diagnosed with ASD. Results: Children with ASD experience a range of sensory sensitivities, attention deficits, hyperactivity, and behavioral resistance, which significantly hinder the performance of adequate oral hygiene practices. These challenges contribute to a lack of effective dental prophylaxis and limited access to regular preventive care, ultimately resulting in poorer oral health outcomes and reduced oral health-related quality of life. Conclusion: Due to the multifaceted characteristics of ASD, children with this condition face significant barriers in accessing appropriate and individualized oral care. This increases their risks of developing oral health disorders, underscoring the need for coordinated efforts between caregivers and dental professionals to improve oral health outcomes in this vulnerable population. Full article

Parkinson’s disease (PD) associated with GBA1 mutations—recently termed Sidransky syndrome—differs from idiopathic PD (iPD) by earlier onset, more rapid progression, and higher rates of non-motor symptoms. Our objective was to assess whether GBA1 mutations contribute to olfactory dysfunction in PD and in asymptomatic carriers of the mutation. We compared olfactory and motor functions in 119 participants: Sidransky syndrome (n = 18), iPD (n = 30), GBA1 variant carriers without PD (n = 21), Gaucher disease patients (n = 20), and healthy controls (n = 30). All were evaluated with the Brief Smell Identification Test (BSIT^®) and the motor part of the Movement Disorders Society Unified PD Rating Scale (MDS-mUPDRS). Mean age was 59.2 ± 11.7 years. Mean disease duration was 2.5 ± 2.2 years in Sidransky syndrome and 5.4 ± 4.9 years in iPD. We found that both PD groups had significantly lower BSIT^® scores than non-PD groups (p < 0.001), particularly for leather, smoke, natural gas, pineapple, clove, rose, and lemon. Sidransky syndrome patients scored lower than iPD patients (p = 0.04). No significant olfactory deficits were observed in GBA1 carriers or Gaucher patients without PD. We conclude that hyposmia is more pronounced in Sidransky syndrome than in iPD. However, normal olfaction in non-parkinsonian GBA1 carriers suggests that GBA1 variants alone do not account for olfactory loss in PD. Hyposmia likely reflects broader PD pathology rather than a direct effect of the GBA1 mutation. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline and complex molecular changes. Extracellular vesicles (EVs), particularly exosomes, play a key role in intercellular communication and disease progression, transporting proteins, lipids, and nucleic acids. While altered exosomal mRNA profiles have emerged as potential biomarkers for AD, the relationship between mRNA expression and AD neuropsychological deficits remains unclear. Here, we investigated the correlation between exosomx10-derived mRNA signatures and neuropsychological performance in a cohort from Barranquilla, Colombia. Expression profiles of 16,585 mRNAs in 15 AD patients and 15 healthy controls were analysed using Generalized Linear Models (GLMs) and the Predictive Power Score (PPS). We identified significant correlations between specific mRNA signatures and key neuropsychological variables, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Functional Assessment Screening Tool (FAST), Boston Naming Test, and Rey–Osterrieth Figure test. These mRNAs were in key AD-associated genes (i.e., GABRB3 and CADM1), while other genes are novel (i.e., SHROOM3, SLC7A2, GJB4, and XBP1). PPS analyses further revealed predictive relationships between mRNA expression and neuropsychological variables, accounting for non-linear patterns and asymmetric associations. If replicated in more extensive and heterogeneous studies, these findings provide critical insights into the molecular basis governing the natural history of AD, potential personalized and non-invasive diagnosis, prognosis, follow-up, and potential targets for future therapies. Full article

Deep learning (DL) approaches to natural language processing (NLP) offer powerful tools for creating digital twins (DTs) of patients in psychiatry and neurological rehabilitation by processing unstructured textual data such as clinical notes, therapy transcripts, and patient-reported outcomes. Techniques such as transformer models (e.g., BERT, GPT) enable the analysis of nuanced language patterns to assess mental health, cognitive impairment, and emotional states. These models can capture subtle linguistic features that correlate with symptoms of degenerative disorders (e.g., aMCI) and mental disorders such as depression or anxiety, providing valuable insights for personalized treatment. In neurological rehabilitation, NLP models help track progress by analyzing a patient’s language during therapy, such as recovery from aphasia or cognitive decline caused by neurological deficits. DL methods integrate multimodal data by combining NLP with speech, gesture, and sensor data to create holistic DTs that simulate patient behavior and health trajectories. Recurrent neural networks (RNNs) and attention mechanisms are commonly used to analyze time-series conversational data, enabling long-term tracking of a patient’s mental health. These approaches support predictive analytics and early diagnosis by predicting potential relapses or adverse events by identifying patterns in patient communication over time. However, it is important to note that ethical considerations such as ensuring data privacy, avoiding bias, and ensuring explainability are crucial when implementing NLP models in clinical settings to ensure patient trust and safety. NLP-based DTs can facilitate collaborative care by summarizing patient insights and providing actionable recommendations to medical staff in real time. By leveraging DL, these DTs offer scalable, data-driven solutions to promote personalized care and improve outcomes in psychiatry and neurological rehabilitation. Full article

Neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurogenetic disorders caused by mutations in 14 different genes. CLN6 disease manifests as variant late-infantile NCL (vLINCL) or as an adult variant. In childhood, symptoms include speech delay, vision loss, cognitive and motor decline, seizures, and early death. An in-depth characterization of a naturally occurring Cln6 mutant mouse (Cln6^nclf) is presented, with implications for translational research. The expanded phenotype provides data showing early death, vision loss, and motor deficits in male and female Cln6^nclf mice. Diminished visual acuity in Cln6^nclf mice was noted at 28 weeks of age, but the pathological loss of retinal layers began as early as 2 weeks or postnatal day 14 (P14). Apoptosis was confirmed by TUNEL staining in the Cln6^nclf mouse brain at P8 and in the retina at P12. A peak in glial fibrillary acidic protein (GFAP) expression was established as a normal developmental phenomenon in the wild-type and Cln6^nclf mouse brain cerebellum and the CA2–CA3 regions of the hippocampus at P8. In Cln6^nclf mice, GFAP levels were elevated at P12 in the cerebellum and hippocampus. In the retina, a developmental peak in gliosis was absent, with increased astrogliosis noted at P6 and P8 in female and male Cln6^nclf mice, respectively. This highlights the lack of a sex-dependent response in wild-type mice. These novel data position the Cln6^nclf mouse model as a useful tool for screening potential therapeutics for human CLN6 disease. Full article

Functional differences in key brain networks, including the dorsal attention network (DAN), control network (CN), and default mode network (DMN), have been identified in individuals with obsessive–compulsive disorder (OCD). However, the precise nature of these differences remains unclear. In this study, we further explored these differences and validated previous findings using a novel edge functional connectivity (eFC) approach, which enables a more refined analysis of brain network interaction. By employing this advanced method, we sought to gain deeper insights into FC alterations that may underlie the pathology of OCD. We collected data during movie watching from 44 patients with OCD and 33 healthy controls (HCs). The two-sample t test was used to assess differences in entropy between the DAN, CN, and DMN between groups. The analysis was performed with control for potentially confounding variables to ensure the robustness of the findings. Significant differences in network entropy were found between the OCD and HC groups. Relative to HCs, patients with OCD showed significantly reduced entropy in the DAN and increased entropy in the CN and DMN. The decreased entropy in the DAN and increased entropy in the CN and DMN observed in this study may be related to the core symptoms of OCD, such as attention deficit, impaired cognitive control, and self-referential thinking. These results provide valuable insights into the neurobiological mechanisms of OCD and highlight the potential of network entropy as a biomarker for the disorder. Future research should further explore the relationship between these network changes and the severity of OCD symptoms, as well as assess their implications for the development of treatment strategies. Full article

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that significantly impacts learning, daily functioning, and personal development. Astaxanthin (ASTA), a naturally occurring antioxidant, has garnered interest as a potential therapeutic agent for various diseases, particularly in mitigating oxidative stress. This study explores a novel application of ASTA in the context of ADHD, aiming to investigate its therapeutic effects and underlying mechanisms. Spontaneously hypertensive rats (SHRs), widely used ADHD model animals, were treated with ASTA (50/100 mg/kg/day) for three weeks, 5 mg/kg/day atomoxetine (ATO) as the positive, and Wistar Kyoto (WKY) rats as control. Behavioral improvements were assessed using the open field test (OFT) and the Morris water maze (MWM). Biochemical analyses were conducted to evaluate changes in the levels of various neurotrophic factors, while histological examinations were performed to assess neuroprotective effects. Additionally, the role of ASTA in the brain–gut axis was investigated. The behavioral symptoms of hyperactivity, anxiety, and impaired spatial memory in ADHD animals were mitigated by ASTA. This improvement is primarily attributed to the restoration of neurotransmitter levels, particularly dopamine (DA), achieved through the modulation of several critical components within the dopamine system, including dopamine receptor 1 (DR1), dopamine transporter (DAT), tyrosine hydroxylase (TH), and synaptic-associated protein 25 (SNAP-25). Additionally, regulating the serotonin transporter (SERT) and glial cell-derived neurotrophic factor (GDNF) supports the recovery of serotonin levels and facilitates optimal brain development. Furthermore, cerebellar cells were protected, and the structure of the intestinal microbiota was regulated. ASTA can mitigate ADHD symptoms in SHR through the modulation of the dopaminergic system, multiple neurotransmitters, neurotrophic factors, and the neuro-intestinal environment, which establishes ASTA as a promising nutraceutical candidate for adjunctive therapy in pediatric ADHD. Full article

The Askisi-Spelling Deficits (SD) neuropsychological web-based screener was developed to assess cognitive and spelling abilities in children, with an emphasis on the early detection of spelling disorders. This tool incorporates six tasks that evaluate cognitive domains, such as visual and auditory working memory, response inhibition, and spelling processing, providing a comprehensive framework for assessment. A study conducted with 264 Greek children, including 132 children with spelling deficits and 132 typically developing controls, aimed to implement this screening tool. Results indicated that the screener was effective, as children with spelling deficits showed significantly lower performance and longer response times across all tasks. The tool’s internal consistency was supported by split-half correlations (r = 0.64) and Spearman–Brown coefficients (r = 0.78). Nonetheless, certain limitations were identified, including the absence of latency data for specific tasks (Go/No-Go and working memory), as well as the screener’s cultural specificity, which might limit its applicability to other linguistic and orthographic systems. Future iterations should prioritize the inclusion of timing mechanisms for more detailed assessments and consider adaptations for use in languages with varying orthographic complexities. Expanding the demographic reach and conducting longitudinal validation studies would further improve its utility and generalizability. The web-based nature of the screener enables scalable and standardized administration, making it a practical and efficient tool for the early identification of spelling difficulties in children. Full article

The excitation/inhibition (E/I) balance is a critical feature of neural circuits, which is crucial for maintaining optimal brain function by ensuring network stability and preventing neural hyperexcitability. The hippocampus exhibits the particularly interesting characteristics of having different functions and E/I profiles between its dorsal and ventral segments. Furthermore, the hippocampus is particularly vulnerable to epilepsy and implicated in Fragile X Syndrome (FXS), disorders associated with heightened E/I balance and possible deficits in GABA-mediated inhibition. In epilepsy, the ventral hippocampus shows heightened susceptibility to seizures, while in FXS, recent evidence suggests differential alterations in excitability and inhibition between dorsal and ventral regions. This article explores the mechanisms underlying E/I balance regulation, focusing on the hippocampus in epilepsy and FXS, and emphasizing the possible mechanisms that may confer homeostatic flexibility to the ventral hippocampus in maintaining E/I balance. Notably, the ventral hippocampus in adult FXS models shows enhanced GABAergic inhibition, resistance to epileptiform activity, and physiological network pattern (sharp wave-ripples, SWRs), potentially representing a homeostatic adaptation. In contrast, the dorsal hippocampus in these FXS models is more vulnerable to aberrant discharges and displays altered SWRs. These findings highlight the complex, region-specific nature of E/I balance disruptions in neurological disorders and suggest that the ventral hippocampus may possess unique compensatory mechanisms. Specifically, it is proposed that the ventral hippocampus, the brain region most prone to hyperexcitability, may have unique adaptive capabilities at the cellular and network levels that maintain the E/I balance within a normal range to prevent the transition to hyperexcitability and preserve normal function. Investigating the mechanisms underlying these compensatory responses in the ventral hippocampus and their developmental trajectories may offer novel insights into strategies for mitigating E/I imbalances in epilepsy, FXS, and potentially other neuropsychiatric and neurodevelopmental disorders. Full article

Background/Objectives: The purpose of this research was to investigate the effects of bisphenol A (BPA) exposure on neurobehavioral testing in young Wistar rats and to evaluate the therapeutic potential of Thymus ciliatus (TEO) essential oil to attenuate the damage induced by this chemical toxin. Methods: The essential oil was extracted by hydro-distillation (yield of 2.26%), and the characterization by GC-MS indicates that the major components of Thymus ciliatus oil are thymol (63.33%), p-cymene (13.4%), and σ-terpinene (6.69%). Acute BPA intoxication was induced with a dose of 50 mg/kg orally for 60 days. The neurobehavioral evaluation, performed using a comprehensive set of tests including the forced swim test, dark/light box, Morris water maze, open field test, and sucrose preference test, clearly demonstrated that bisphenol A (BPA) exposure induced significant neurobehavioral impairments. Results: These impairments included reduced exploratory behavior indicative of heightened stress, anxiety, and depressive-like states, as well as deficits in memory and learning. Furthermore, BPA intoxication was associated with metabolic disturbances such as hyperglycemia along with histopathological evidence of brain tissue damage. However, TEO treatment attenuated these adverse effects by restoring neurobehavioral function. Molecular docking analysis revealed an affinity between the major essential oils identified in T. ciliatus, BPA, and the 5HT2C receptor and the MAO, AChE, and BChE enzymes, suggesting a potential mechanism underlying BPA’s effects on behavior and memory. In addition, TEO also showed an interaction with these molecules, suggesting a therapeutic potential against BPA. These findings underscore the promising role of TEO in mitigating the poisonous effects of BPA and pave the way for additional research into the molecular mechanisms and therapeutic uses of natural bioactive compounds for the prevention and treatment of toxic diseases. Thymol, the major compound in TEO, exhibited activity related to the dopamine and serotonin pathways, so it could have potential antidepressant properties. Conclusions: Thymol might be a promising candidate for the treatment of neurodegenerative and neurological disorders such as depression, Parkinson’s disease, and Alzheimer’s disease while also preventing histological damage in the brain. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, neuroinflammation and neuronal damage. This study aimed to investigate the neuroprotective effects of cilomilast (CILO), a phosphodiesterase-4 (PDE4) inhibitor, alone and in combination with chlorogenic acid (CGA), a natural polyphenol, against scopolamine (SCOP)-induced cognitive impairment in mice. Forty male albino mice were divided into five groups: normal control, SCOP control, CGA + SCOP, CILO + SCOP and CILO + CGA + SCOP. Behavioral assessments, including the Y-maze and pole climbing tests, demonstrated that SCOP significantly impaired cognition, while treatment with CILO and CGA reversed these deficits, with the combination group showing the greatest improvement. Histopathological analyses revealed that CILO and CGA reduced neuronal damage and amyloid beta (Aβ) accumulation. Immunohistochemical and biochemical assessments confirmed a decrease in neuroinflammatory markers, including tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa B (NF-κB). Molecular analyses showed that CILO restored cyclic adenosine monophosphate (cAMP) levels, leading to activation of protein kinase A (PKA), cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF), key regulators of neuronal plasticity and survival. CGA enhanced these effects by further inhibiting PDE4, amplifying the neuroprotective response. These findings suggest that PDE4 inhibitors, particularly in combination with CGA, may represent promising therapeutic strategies for AD-related cognitive impairment. Full article

In recent decades, substantial evidence has highlighted the integral roles of neuroglia, particularly astrocytes, microglia, oligodendrocytes, and ependymal cells, in the regulation of synaptic transmission, metabolic support, and immune mechanisms within the central nervous system. In addition to their structural role, these cells actively modulate neurotransmitter homeostasis and influence neuronal plasticity, thereby affecting cognition, mood, and behavior. This review discusses how neuroglial alterations contribute to the pathophysiology of five common psychiatric disorders: major depression, bipolar disorder, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and schizophrenia. We synthesized preclinical and clinical findings illustrating that glial dysfunction, including impaired myelination and aberrant neuroinflammatory responses, often parallels disease onset and severity. Moreover, we outline how disruptions in astrocytic glutamate uptake, microglia-mediated synaptic pruning, and blood–brain barrier integrity may underlie the neurobiological heterogeneity observed in these disorders. The therapeutic implications range from anti-inflammatory agents to investigational compounds that aim to stabilize glial function or promote remyelination. However, challenges due to interindividual variability, insufficient biomarkers, and the multifactorial nature of psychiatric illnesses remain. Advances in neuroimaging, liquid biopsy, and more precise molecular techniques may facilitate targeted interventions by stratifying patient subgroups with distinct glial phenotypes. Continued research is essential to translate these insights into clinically efficacious and safe treatments. Full article

Nanomotors driven by endogenous enzymes are favored in biology and pharmacy due to their spontaneous driving and efficient biocatalytic activity, and have potential applications in the treatment of clinical diseases that are highly dependent on targeted effects. For diseases such as muscle atrophy, using energy molecules such as ATP to improve cellular metabolism is a relatively efficient treatment method. However, traditional adenosine triphosphate (ATP) therapies for muscle atrophy face limitations due to instability under physiological conditions and poor targeting efficiency. To address these challenges, we developed an endogenous proton-gradient-driven ATP transport motor (ATM), a nanomotor integrating chloroplast-derived F_oF₁-ATPase with a biocompatible flask-shaped organic shell (FOS). The ATM is synthesized by vacuum-injecting phospholipid-embedded F_oF₁-ATPase nanothylakoids into ribose-based FOS, enabling autonomous propulsion in acidic microenvironments through proton-driven negative chemotaxis (directional movement away from regions of higher proton concentration). This nanomotor converts proton gradients into ATP synthesis, directly replenishing cellular energy deficits in atrophic tissues. In vitro studies demonstrated high biocompatibility (>90% cell viability at 150 μg/mL) and pH-responsive motility, achieving speeds up to 4.32 μm/s under physiological gradients (ΔpH = 3). In vivo experiments using dexamethasone-induced muscle atrophy mice revealed that ATM treatment accelerated weight recovery and restored normal muscle morphology, with treated mice exhibiting cell sizes comparable to healthy controls (30–40 μm vs. 15–25 μm in untreated). These results highlight the ATM’s potential as a precision therapeutic platform for metabolic disorders, leveraging the natural enzyme functionality and synthetic material design to enhance efficacy while minimizing systemic toxicity. Full article