Search Results (480)

Developmental dyslexia is a common neurodevelopmental disorder characterized by persistent difficulties in accurate and fluent word reading despite adequate intelligence, educational opportunity, and intact sensory function. Contemporary neurobiological models have progressively shifted from localization-based explanations toward network-oriented perspectives emphasizing large-scale brain connectivity, developmental maturation, and neuroplasticity. Nevertheless, the developmental mechanisms underlying early right-hemisphere recruitment remain incompletely understood. Although increased right-hemisphere activation has traditionally been interpreted as a compensatory response to left-hemisphere dysfunction, accumulating evidence from longitudinal neuroimaging, intervention, and developmental studies indicates that this explanation alone does not adequately account for the heterogeneity of neurobiological findings observed across individuals with developmental dyslexia. This narrative review synthesizes evidence from developmental neurobiology, network neuroscience, longitudinal neuroimaging, and intervention research to examine the biological processes underlying early right-hemisphere recruitment. Across the reviewed literature, developmental dyslexia is increasingly characterized by atypical maturation of distributed reading networks involving alterations in white-matter development, functional connectivity, hemispheric lateralization, and experience-dependent neuroplasticity. Collectively, these findings suggest that reading networks remain dynamically modifiable throughout literacy acquisition and that multiple developmental pathways may contribute to diverse neurobiological and behavioral outcomes. Building on this evidence, we propose a Developmental Neuroplasticity Framework for Reading Network Reorganization that integrates existing neurobiological models within a unified developmental perspective. Rather than proposing a new neurobiological mechanism, the framework seeks to explain the heterogeneous patterns of early right-hemisphere recruitment that are not fully accounted for by compensation-based interpretations alone. Specifically, it conceptualizes early right-hemisphere recruitment as one possible adaptive developmental outcome emerging from interactions among early neurodevelopmental vulnerability, distributed network connectivity, developmental neuroplasticity, and environmental experience. By integrating evidence that has largely been considered within separate theoretical perspectives, the framework generates empirically testable predictions regarding developmental trajectories, network reorganization, and intervention-related variability, while providing a conceptual basis for earlier identification of children at risk and the development of more targeted, developmentally informed intervention strategies. Full article

Physical education (PE) is commonly justified through its contributions to physical fitness, motor skill development, sport participation, and health-enhancing physical activity. These aims remain important, but they do not fully capture PE’s potential as a curriculum context for lifestyle learning and neurobehavioral well-being. This narrative review used structured literature mapping and conceptual framework development to examine how PE may connect embodied movement experiences with motivation, stress and emotion regulation, self-efficacy, resilience, recovery-related awareness, and lifestyle self-regulation in adolescents and young adults. Literature searches were conducted iteratively in PubMed, Scopus, Web of Science Core Collection, SPORTDiscus, and ERIC, with the final search update completed on 20 June 2026. The synthesis identified a curriculum-to-lifestyle gap: existing evidence more often examines whether PE, physical activity, sport, or physical literacy is associated with health or psychological outcomes than how curriculum, teaching climate, reflection, assessment, and peer interaction may support transferable self-regulatory learning. The review therefore proposes an evidence-informed, curriculum-oriented conceptual framework linking PE design and pedagogy with proximal motivational, emotional, cognitive-regulatory, behavioral, and embodied processes. The framework does not imply that PE automatically improves mental health, directly produces neurobiological change, or replaces specialist care. Evidence is stronger for proximal educational processes than for sustained transfer beyond PE. Future research should test clearly specified curriculum mechanisms, implementation conditions, assessment approaches, and longitudinal transfer. Full article

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by impairments in social communication, restricted and repetitive behaviors, sensory dysregulation, and frequent psychiatric comorbidities. Increasing attention has been directed toward acupuncture as a complementary neuro-modulatory intervention; however, its underlying molecular mechanisms remain incompletely understood. This review synthesizes evidence from preclinical, clinical, and molecular studies published between 2015 and 2025 to examine how acupuncture influences neurobiological pathways relevant to ASD. Current evidence indicates that acupuncture modulates multiple neurotransmitter systems, including glutamatergic, GABAergic, dopaminergic, serotonergic, and noradrenergic signaling, while also influencing neurotrophin-mediated plasticity, neuroinflammatory responses, and synaptic function. Studies conducted directly in ASD models demonstrate regulation of excitatory/inhibitory balance, monoaminergic signaling, neurotrophin pathways, and ASD-associated behavioral outcomes, whereas evidence from related neuropsychiatric conditions provides complementary mechanistic support for these pathways. Collectively, the findings suggest that acupuncture may act through coordinated modulation of interconnected neurotransmitter and neuroplasticity networks rather than a single molecular target. However, direct mechanistic evidence in ASD-specific models and clinical populations remains limited, and considerable heterogeneity exists among acupuncture protocols and outcome measures. Future studies integrating standardized stimulation paradigms with molecular, electrophysiological, neuroimaging, and behavioral assessments will be essential to validate the proposed mechanisms and clarify the translational potential of acupuncture in ASD. Full article

Attention-deficit/hyperactivity disorder (ADHD) is traditionally defined by symptoms of inattention, hyperactivity, and impulsivity. However, growing evidence suggests that this framework incompletely reflects the underlying neurobiology and clinical heterogeneity of the disorder, particularly in females. Current models of dopaminergic neurotransmission propose that ADHD is characterized not by simple dopamine deficiency but by dysregulation of tonic and phasic dopamine signaling. Theoretical models propose that reduced tonic dopamine activity may coexist with enhanced stimulus-dependent phasic responses in ADHD. Whether such signaling differences produce alternating states of underactivation and hyperactivation within the same individual has not been directly demonstrated and constitutes a central hypothesis of the present framework. In this narrative hypothesis paper, I examine evidence linking dopaminergic dysregulation to a broader ADHD phenotype encompassing four functional domains: energy regulation, attention allocation, behavioral activation, and emotional reactivity and awareness. Within these domains, hyperactivity and hypoactivity, inattention and hyperfocus, impulsive responding and difficulty initiating action, and emotional hyperreactivity and alexithymia are treated as potentially related manifestations rather than established psychometric opposites. Neuroimaging studies report alterations in dopamine transporter and receptor availability, while clinical and behavioral studies document associations between ADHD and different, sometimes contrasting manifestations within the proposed domains. Importantly, internally experienced manifestations such as emotional dysregulation, hypoactivity, procrastination, and hyperfocus appear particularly relevant to female presentations of ADHD. I propose that ADHD should be conceptualized as a multidimensional disorder of dopaminergic regulation. This framework may better explain phenotypic diversity, improve identification of underrecognized presentations, and guide future biomarker-driven and precision-medicine approaches to ADHD. Full article

Background/Objectives: Substance use behaviors share a complex, overlapping polygenic architecture, yet translating genome-wide association study (GWAS) findings into actionable biological mechanisms remains challenging. This study aimed to characterize the genetic architecture of five substance use traits (alcohol consumption, alcohol dependence, nicotine use, illicit drug use, and behavioral disinhibition) and identify shared and distinct gene expression signatures within the neural circuits governing addiction. Methods: We reanalyzed 7188 individuals from the Minnesota Center for Twin and Family Research (MCTFR) cohort utilizing longitudinal composite phenotypes spanning five substance-use domains and general behavioral disinhibition. Post-QC, 6874 individuals were retained for downstream analysis. Following genomic imputation and linear mixed model GWAS (GEMMA), we utilized the SNipar framework to partition polygenic risk scores (PRS) into direct and indirect genetic effects, investigating intergenerational shifts in genetic penetrance and effects of assortative mating. Finally, we integrated our summary statistics with brain tissue reference panels to perform a transcriptome-wide association study (TWAS) modeling genetically regulated gene expression within neural circuits relevant to addiction. Results: Partitioning of polygenic risk revealed that while surface-level parental DNA correlations were modest (r = 0.08), underlying latent genetic correlations approached unity (R_δ ≈ 0.99), indicating that addiction risk clustering in families is driven by intense assortive mating and concentrated biological inheritance. Multi-phenotype TWAS identified several significant gene–phenotype associations—notably ADAM32 and SLC9A3, which demonstrated pleiotropic effects across multiple substance use categories. Crucially, these significant TWAS signals were enriched in striatal structures (caudate, putamen, substantia nigra) and frontal cortical regions. Conclusions: Our findings support a model of shared genetic liability across diverse substance use behaviors, mediated by specific gene expression patterns in the mesolimbic dopamine system and frontal cortex. By integrating multi-phenotype GWAS and TWAS, this study highlights pleiotropic candidate genes and provides critical insights into the tissue-specific neurobiological pathways underlying addiction vulnerability. Full article

Magnesium is an essential mineral involved in numerous physiological and neurobiological processes. However, the biological effects of distinct Mg forms remain insufficiently characterized. This study compared the systemic and neurobiological effects of a multi-form Mg supplement (Magnesium Breakthrough™, Mg BT™, BIOptimizers, Reno, NV, USA) with commonly used single-form Mg compounds in a rat model. Sixty-day-old male Wistar rats were assigned to a control group or to groups receiving Mg BT™ or individual Mg compounds (oxide, citrate or glycinate). Treatments were administered by gastric gavage for 30 days at 50 mg/kg/day of elemental Mg. A comprehensive panel of endpoints was evaluated, including Mg distribution in biological fluids and tissues, metabolic markers, glucose tolerance, synaptic protein expression (synaptophysin, PSD95, phospho-PSD95, drebrin), cortical gene expression (NR2B, BDNF), behavioral outcomes, and liver and kidney histology. Magnesium from the multi-form supplement increased serum Mg without affecting glucose homeostasis and modulated proteins involved in synaptic plasticity, accompanied by mild anxiolytic-like effects without changes in locomotion. No adverse histological alterations were observed, while preserved renal CLDN-19 expression indicated maintained tubular integrity. These findings suggest that supplementation with the multi-form Mg BT™ supplement influences multiple evaluated biological domains, including systemic, behavioral and molecular parameters, with effects comparable to those observed with individual magnesium compounds under the experimental conditions applied. Full article

Post-traumatic stress disorder (PTSD) is a severe condition triggered by traumatic exposure, characterized by symptoms like trauma re-experiencing, avoidance, mood alterations, hypervigilance, and sleep disturbances. While its exact mechanisms remain uncertain, PTSD involves dysregulation across neurobiological systems underlying fear conditioning, threat appraisal, executive control, and stress response. Although research highlights the sympathetic–adreno–medullary (SAM) system and the hypothalamic–pituitary–adrenal (HPA) axis, findings on stress-related mediators remain inconsistent regarding their precise contributions over time. To address this, we propose a hypothetical model viewing PTSD as a multistable system shifting from physiological to pathological steady states. We assume that intense, repeated emotional stress triggers spike activation in the amygdala, driving an amygdala–locus coeruleus loop into a high-activation state via reciprocal excitation, mediated by corticotropin-releasing hormone (CRH) and noradrenaline. This sequentially alters amygdala–hippocampus and prefrontal cortex loops, reinforcing fear expression and impairing extinction. This model is consistent with key features of PTSD, including its higher prevalence among females, increased glucocorticoid receptor sensitivity, the frequently observed hypocortisolism, and the partial efficacy of serotonin and norepinephrine reuptake inhibitor (SNRI) and CRH receptor antagonists. While requiring experimental validation, this framework connects molecular, circuit, and behavioral data to help identify novel interventions for restoring adaptive stress-response dynamics. Full article

Ciprofloxacin (CPX) has been associated with neuropsychiatric adverse effects; however, its contribution to depression-like behaviors and the underlying neurobiological mechanisms remain insufficiently characterized. Previous studies have indicated that cinnamic acid (CA) may exert protective actions in the nervous system by modulating oxidative and inflammatory pathways. Nevertheless, its effectiveness in preventing CPX-induced neurobehavioral impairments remains largely unknown. The present study aimed to investigate whether CA attenuates CPX-induced depression-like behaviors through modulation of neuroinflammation and oxidative stress. This study included 60 male Swiss albino mice distributed among six experimental groups (n = 10). Animals were assigned to receive a vehicle, CPX administered at 80 mg/kg, CPX combined with CA at doses of 50, 100, or 200 mg/kg, or CPX together with FLX (20 mg/kg) throughout the 14-day treatment period. Behavioral alterations were assessed using social interaction, forced swimming, tail suspension, and sucrose preference paradigms. In addition, hippocampal and prefrontal cortex tissues were examined for oxidative stress markers (MDA, GSH, and CAT), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and neurotransmitters (serotonin, dopamine, and GABA) using ELISA-based assays. CPX administration induced significant depression-like behaviors, evidenced by reduced social interaction, increased immobility, and anhedonia (p < 0.05). These behavioral alterations were associated with increased lipid peroxidation, impaired antioxidant defense, elevated pro-inflammatory cytokine levels, and decreased monoaminergic and GABAergic neurotransmission in both HIP and PFC regions. CA treatment significantly improved CPX-induced behavioral and neurochemical alterations. Among the tested doses, the 100 mg/kg regimen produced the most consistent response, accompanied by reduced neuroinflammatory activity and restoration of neurotransmitter levels, particularly in the hippocampus. In conclusion, CA mitigated CPX-induced behavioral deficits and neurochemical alterations, an effect that may be attributed to its regulatory influence on oxidative stress, neuroinflammatory processes, and neurotransmitter balance within the HIP–PFC pathway. Collectively, the findings indicate that CA may have therapeutic relevance in reducing the neuropsychiatric consequences associated with CPX exposure. Full article

Stress is a major influencing behavior, health, and welfare in free-roaming dogs, particularly in environments characterized by unpredictability, social instability, and frequent human interactions. Although research on canine stress responses has expanded considerably, current knowledge remains fragmented across the neurobiological, physiological, and behavioral domains, limiting the development of comprehensive welfare assessment strategies. Importantly, free-roaming and shelter-housed dogs should not be viewed as entirely separate populations, since many shelter dogs originate from free-roaming environments and share similar stress-related experiences. This narrative review provides a comprehensive synthesis of current evidence on stress mechanisms in free-roaming and shelter-housed dogs The literature was explored across major scientific databases, and a total of 69 relevant studies were included. Particular emphasis was placed on the activation and regulation of the hypothalamic–pituitary–adrenal (HPA) axis, associated neuroendocrine alterations, and their behavioral expression. The strengths and limitations of commonly used physiological indicators, including cortisol measured in blood, saliva, feces and hair, were critically examined in relation to their applicability in real-world contexts. Behavioral manifestations of stress, such as fear- and anxiety-related responses, aggression, withdrawal, and stereotypic behaviors, were analyzed as functional outcomes of neurobiological activation and environmental challenges. Environmental stressors typical of shelter conditions as well as the role of human–dog interactions in stress modulation are also discussed. By combining neurobiological, physiological, and behavioral perspectives, this review highlights the importance of multidimensional stress assessment and proposes a conceptual framework linking biological mechanisms with observable behavioral indicators of welfare across the continuum from free-roaming to shelter environments. These findings may support the development of evidence-based welfare assessment and management strategies for free-roaming and shelter-housed dog populations. Full article

Background/Objectives: The rates of obesity and binge-eating disorder (BED) have increased markedly over the last few decades. The onset of these conditions has been associated in part with the disruption of neural pathways that regulate food reward. Existing literature has implicated the endogenous opioid system as an important mediator of pleasure and reinforcing behaviors associated with food intake. While the relationship between opioids and food intake has been studied extensively, how dysregulated opioid signaling contributes to compulsive eating still remains unclear. Therefore, the aim of this review is to analyze the role of opioid peptides and receptors, and their interactions with dopamine in hedonic feeding. Methods: We conducted a narrative review of preclinical and clinical trials, incorporating studies that were relevant to opioid-mediated feeding and food reward. Results: β-endorphins appear to modulate the hedonic value of food, but their effects appear to be context-dependent. Enkephalins may influence motivational drive toward food, while nociceptin signaling has been linked to the preferential consumption of palatable foods under binge-like conditions. Consistent with these findings, NOP antagonism has been reported to reduce binge-like intake of a high-fat diet (HFD) without affecting homeostatic eating patterns. Lastly, chronic mu-opioid receptor (MOP) activation by palatable foods may induce neuroadaptive changes, including receptor desensitization, dopamine D2 receptor downregulation, and reward hypofunctionality, which overlap with mechanisms associated with substance use disorders. Conclusions: Altered MOP signaling may disrupt the hedonic and behavioral mechanisms that regulate feeding behavior. Pharmacological therapies targeting opioid and opioid-dopamine interactions may show promise for treating obesity and BED. However, additional research is still needed to clarify peptide-specific mechanisms, sex differences, and long-term neurobiological consequences associated with hedonic and compulsive eating. Full article

Depression is increasingly recognized as a multifactorial disorder involving immune, metabolic, and neurobiological disturbances that extend beyond classical monoaminergic hypotheses. Among xenobiotic-based experimental approaches, lipopolysaccharide (LPS) has become a valuable tool for investigating how peripheral inflammatory stimuli are translated into central neurobiological dysfunction. This narrative review aimed to integrate current evidence regarding the mechanisms by which LPS-induced neuroimmune activation contributes to depression-related phenotypes and to discuss the translational relevance of these findings. Literature searches were performed in PubMed, ScienceDirect, and Google Scholar, focusing on studies addressing inflammatory signaling, oxidative imbalance, inflammasome activation, neurotransmitter dysfunction, and experimental modeling strategies. Current evidence suggests that LPS-induced neuroinflammation involves a dynamic interaction between peripheral immune signaling, mitochondrial dysfunction, redox imbalance, and glial activation, establishing self-amplifying mechanisms capable of sustaining chronic inflammatory states. Such alterations profoundly affect kynurenine metabolism, glutamatergic homeostasis, and reward-related neurotransmission, thereby contributing to synaptic dysfunction and behavioral impairment. Experimental findings obtained from animal, cellular, and computational platforms further support the emergence of integrated therapeutic strategies targeting multiple neuroimmune pathways. Collectively, these observations reinforce the concept that neuroinflammation represents a central biological interface linking xenobiotic exposure to depressive-like behavior. Full article

Obesity is one of the most serious public health challenges worldwide and has reached the scale of a global epidemic. Its etiology is multifactorial and includes genetic, environmental, hormonal, and neurobiological factors. In recent years, increasing attention has been paid to the role of the gut microbiota in the regulation of energy metabolism, inflammatory processes, and the functioning of the gut–brain axis. An increasing body of evidence suggests that the gut microbiota may influence the dopaminergic system and eating behaviors through bacterial metabolites, immune pathways, and the vagus nerve. Disturbances in microbiota composition may contribute to the development of chronic low-grade inflammation and compulsive consumption of highly processed foods. This article discusses the concept of food addiction as a phenomenon involving loss of control over eating, excessive reward system reactivity, and dopaminergic dysfunction within the mesolimbic reward system. Particular attention is given to the role of the gut microbiota in modulating these processes, including the potential effects of selected commensal bacteria and the importance of dietary interventions such as the ketogenic diet in regulating the gut–brain axis. The presented data suggest that modulation of the gut microbiota may represent a promising supportive strategy in the treatment of obesity and disorders associated with compulsive eating. At the same time, it is emphasized that the current state of knowledge is largely preclinical and observational, highlighting the need for further translational and clinical studies. Full article

Background/Objectives: Antipsychotic dosing for behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease remains empirical and variable. This study develops a deep learning model to predict individualized antipsychotic doses from structural MRI. Methods: A transfer learning approach with a cascaded ResNet (Cas-ResNet) was used. The model was first pre-trained on a large healthy aging dataset (CBMFM, n = 646) for brain age prediction, then fine-tuned on a BPSD dataset (SMHC, n = 86) to predict the defined daily dose (DDD) of antipsychotics. Model interpretability was performed using Grad CAM to identify predictive brain regions. Results: The proposed model achieved a mean absolute error of 0.19 and a Pearson correlation of 0.66 between predicted and actual doses, outperforming baseline 3DCNN, VGG, and DenseNet. Key contributing regions included the left inferior temporal gyrus, right parahippocampal gyrus, right putamen, left middle temporal gyrus, and left caudate. Conclusions: This proof-of-concept study demonstrates that deep learning can predict personalized antipsychotic doses from structural MRI, offering an objective tool to standardize BPSD pharmacotherapy and reduce empirical prescribing. The identified brain regions provide neurobiological insights into treatment response. Full article

Cancer-related cognitive impairment (CRCI), also known as chemobrain or chemofog, is characterized by subjective and/or objective changes in attention, executive functions, memory, and processing speed in patients with non-CNS cancers, particularly women with breast cancer. This structured narrative review synthesizes current evidence on mechanisms, neuropsychological assessment, neuroimaging correlates, clinical and demographic risk factors, emerging artificial intelligence and machine learning applications, and non-pharmacological approaches to CRCI in breast cancer. A structured literature search was conducted using PubMed/MEDLINE, PsycInfo, and Clinical Key up to May 2026, with emphasis on studies published between 2023 and 2026. Peer-reviewed English-language studies involving adult breast cancer populations and addressing predefined thematic domains of CRCI were considered. Given the heterogeneity of study designs, assessment tools, interventions, and outcomes, the findings were synthesized narratively. Current evidence supports a multifactorial model of CRCI involving neurobiological, treatment-related, psychological, and behavioral mechanisms. Neuroinflammation, endocrine disruption, oxidative stress, glial alterations, and structural or functional brain changes may contribute to cognitive symptoms; however, the strength of evidence varies, and many findings remain correlational or preclinical. Non-pharmacological interventions, including cognitive training, physical activity, mindfulness-based and psychological approaches, and multimodal digital programs, appear promising as supportive strategies. However, evidence remains heterogeneous, with benefits more consistently reported for patient-reported outcomes, fatigue, emotional distress, and quality of life than for objective neuropsychological performance. CRCI in breast cancer should be approached as a heterogeneous condition requiring early recognition, standardized assessment, and multidisciplinary supportive care. Future research should prioritize longitudinal designs, harmonized endpoints, and a clearer distinction between subjective and objective outcomes. Full article

Religious psychopathology as a field lies at the intersection of psychiatry, theology, and culture. It addresses scientific discoveries and questions relating to the manifestation of mental health disorders that are expressed through religious content, ideation, and/or behavior. Religious psychopathology, being a multifaceted phenomenon, challenges clinicians, researchers, and religious leaders because it is non-trivial to distinguish between culturally normative religious experiences and pathological symptoms. The present integrative narrative review examines historical perspectives, diagnostic challenges, clinical manifestations, cultural considerations, therapeutic interventions, neurobiological models, ethical issues, and future directions in the field of religious psychopathology. It focuses primarily on literature from 2013 to 2025, while also incorporating selected foundational historical, theoretical, and clinical sources necessary for conceptual clarification. A special emphasis is placed on culturally informed and interdisciplinary approaches. Particular focus is given to approaches that respect spiritual frameworks while concurrently promoting evidence-based mental health care. Full article