Neuropsychiatric Disease and Treatment最新文献

{"title":"Echinocystic Acid Antagonizes Post-Stroke Depression in Mice by Suppressing the JNK/NF-κB Signaling Pathway.","authors":"Dandan Wang, Wei Li, Xuan Zhang, Kaiqi Zhu, Yuzhen Wang, Yaozhuo Cai, Hao Chen, Xueli Cai, Jingping Sun","doi":"10.2147/NDT.S596008","DOIUrl":"10.2147/NDT.S596008","url":null,"abstract":"<p><strong>Background: </strong>Post-stroke depression (PSD), a common neuropsychiatric complication after stroke, affects approximately one-third of stroke survivors and severely impairs recovery and quality of life. Echinocystic acid (EA), a pentacyclic triterpenoid from various medicinal herbs, exhibits anti-inflammatory and anti-depressant properties. However, whether EA exerts neuroprotective and antidepressant effects in PSD remains unknown.</p><p><strong>Objective: </strong>This study aims to determine whether EA alleviates PSD and to explore its potential mechanisms involving the JNK/NF-κB pathway and inflammatory cytokines.</p><p><strong>Methods: </strong>PSD was modeled using middle cerebral artery occlusion/reperfusion (MCAO/R) combined with chronic unpredictable mild stress (CUMS). Following MCAO/R surgery, animals received daily intraperitoneal injections of EA or EA combined with the JNK agonist anisomycin (AN) for 28 consecutive days. The expression of phosphorylated JNK (p-JNK) and phosphorylated NF-κB (p-NF-κB) was analyzed by Western blotting. The levels of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were measured using enzyme-linked immunosorbent assay (ELISA). Depressive-like behaviors and the therapeutic efficacy of EA were assessed through a series of behavioral tests. Furthermore, neuronal necrosis and Nissl body integrity were observed using hematoxylin-eosin (H&E) and Nissl staining, respectively.</p><p><strong>Results: </strong>EA treatment significantly downregulated the expression of p-JNK, p-NF-κB, and inflammatory cytokines. H&E staining revealed that EA reduced neuronal necrosis in the hippocampal dentate gyrus. Consistently, Nissl staining demonstrated that EA increased the number of Nissl bodies in the same region. Furthermore, EA administration alleviated depressive-like behaviors in PSD mice. However, the administration of AN counteracted the suppressive effects of EA on the JNK/NF-κB signaling pathway and reversed the beneficial behavioral outcomes associated with EA treatment.</p><p><strong>Conclusion: </strong>The results indicate that EA mitigates neuronal necrosis, alleviates depression-like behaviors, and alleviates PSD by suppressing JNK/NF-κB pathway activation and inflammatory cytokine production.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"596008"},"PeriodicalIF":3.2,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Nerve Conduction in Alzheimer's vs. Late-Life Depression: A Comparative Study.","authors":"Xiaojuan Li, Xing Zhao, Yongpan Huang, Jiayu Tang","doi":"10.2147/NDT.S611214","DOIUrl":"10.2147/NDT.S611214","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) and late-life depression (LLD) patients both exhibit peripheral motor nerve conduction impairments, but with distinct patterns, highlighting divergent neurophysiological mechanisms in these aging-related disorders.</p><p><strong>Objective: </strong>To compare peripheral nerve conduction function among normal cognition (NC), older adults with AD, and LLD.</p><p><strong>Methods: </strong>All the participants were enrolled and assigned to AD, LLD and aged-matched NC controls (all ≥60 years, n=60, respectively). Sensory conduction of the median and sural nerves, and motor conduction of the median and common peroneal nerves, were assessed. Key parameters included latency, amplitude, and conduction velocity. Group differences were analyzed after adjusting for gender, age, education, height, and comorbid medical conditions.</p><p><strong>Results: </strong>By controlling gender, age, height, education level, and somatic diseases with inter-group differences, compared with NC group, the median nerve motor conduction in AD group showed prolonged proximal latency (3.21 vs. 3.65 ms, <i>P</i>=0.023), reduced amplitude (proximal: 7.30±2.02 vs. 3.89±0.57 mV; distal: 6.13±2.17 vs. 4.12±2.38 mV, both <i>P</i><0.001), and slowed conduction velocity (56.46±5.18 vs. 49.29±6.27 m/s, <i>P</i>=0.002). LLD group exhibited more pronounced latency prolongation (proximal: 3.21 vs. 4.06 ms; distal: 7.18 vs. 7.98 ms, both <i>P</i><0.001) and greater amplitude reduction (proximal: 7.30±2.02 vs. 3.65±0.66 mV; distal: 6.13±2.17 vs. 3.18±1.88 mV, both <i>P</i><0.001). In terms of the common peroneal nerve motor conduction, function AD group had significantly slower conduction velocity (48.88±5.82 vs. 42.85±5.27 m/s, <i>P</i>=0.033). LLD group showed prolonged proximal latency (4.25 vs. 5.77 ms, <i>P</i><0.001). No significant differences were found in sensory conduction parameters across groups after adjustment.</p><p><strong>Conclusion: </strong>Both AD and LLD groups were associated with peripheral motor neuropathy, but the pattern of impairment differs. AD is marked by generalized conduction slowing, while LLD shows more severe latency delays and amplitude loss, suggesting distinct pathophysiological pathways. These findings provide new insights into the peripheral nervous system's involvement in age-related neurocognitive and mood disorders.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"611214"},"PeriodicalIF":3.2,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Evidence of Acetyl-L-Carnitine Use in Mood Disorders-: A Systematic Review and Meta-Analysis.","authors":"Rakesh Kumar, Zahra Hashempour, Sara Shahriarirad, Reza Shahriarirad, Leslie C Hassett, Balwinder Singh, Paul E Croarkin, Marin Veldic, Mark A Frye, Sandeep R Pagali","doi":"10.2147/NDT.S586506","DOIUrl":"10.2147/NDT.S586506","url":null,"abstract":"<p><p>Acetyl-l-carnitine (ALC) is increasingly recognized for its potential psychopharmacological mechanism and role in the treatment of mood disorders, particularly major depressive disorder (MDD) and bipolar disorder (BD). Emerging evidence suggests that ALC levels are reduced in individuals with MDD, and this deficiency may contribute to depressive symptoms through disruptions in mitochondrial fatty acid transport, neuroplasticity, and neurotransmission. This review synthesizes findings from randomized controlled trials, open-label studies, and observational research examining ALC use and clinical outcomes in adults treated with ALC in MDD and BD. A systematic review (n=15) and meta-analysis (n=10) studies (14 randomized controlled trials [RCTs] and 1 open label) involving 809 participants (treatment group: 392; comparator group: 417) revealed that ALC significantly reduces depressive symptoms compared to placebo, with comparable efficacy to standard antidepressants and fewer adverse effects. Subgroup analyses suggest enhanced benefits in older adults and those with treatment-resistant depression. These findings support the potential of ALC as both a biomarker and a therapeutic agent in mood disorders. Further large-scale, longitudinal studies are needed to clarify its clinical utility and mechanistic pathways in mood disorders.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"586506"},"PeriodicalIF":3.2,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13242760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of Traditional Chinese Medicine and Psychotherapy in Mental Health: A Narrative Review of Mechanisms, Clinical Evidence, and Future Directions.","authors":"Ji Du, Yong Tan","doi":"10.2147/NDT.S607443","DOIUrl":"10.2147/NDT.S607443","url":null,"abstract":"<p><strong>Purpose: </strong>This narrative review critically evaluates the integration of Traditional Chinese Medicine (TCM) and Western psychotherapy in mental health care, identifying current evidence, methodological limitations, and future research priorities.</p><p><strong>Methods: </strong>We narratively synthesized peer-reviewed literature focusing on clinical studies that combined TCM interventions (acupuncture, herbal medicine, TCM exercises such as Baduanjin and Tai Chi) with psychological or psychiatric approaches for mental disorders. Evidence was organized into three levels: clinical efficacy (human RCTs and meta-analyses), mechanistic studies (animal and biomarker research), and exploratory investigations (neuroimaging, omics, observational surveys).</p><p><strong>Results: </strong>Key findings include: (1) TCM interventions combined with pharmacological or psychological treatments for depression showed a pooled standardized mean difference of -2.05 (95% CI: -2.74 to -1.37) from 18 RCTs, indicating a large effect size but with high heterogeneity; (2) TCM exercises (Baduanjin, Tai Chi) improved attention and reduced mild anxiety (P=0.034), though evidence in clinical samples remains limited; (3) Mechanistic studies suggest potential regulation of the HPA axis, monoamine neurotransmitters, inflammation, and gut microbiota, but these findings are preliminary and derived mostly from animal models. Major barriers to integration include: lack of standardized TCM diagnostic criteria; few methodologically rigorous RCTs; high heterogeneity; insufficient cross-training of clinicians; and fundamental conceptual differences between TCM (holistic) and evidence-based psychotherapy (mechanistic).</p><p><strong>Conclusion: </strong>While TCM-psychotherapy integration holds conceptual promise, current evidence is limited by substantial methodological weaknesses. The most robust evidence exists for acupuncture and TCM exercises for depression and anxiety over short-term follow-up (4-12 weeks). Evidence for PTSD, severe mental illness, and long-term outcomes (≥6 months) remains preliminary. Future research should prioritize large, well-blinded RCTs with prespecified TCM syndrome criteria and longer follow-up periods.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"607443"},"PeriodicalIF":3.2,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13242814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Role of AI Assistants in Accelerating Neurodegenerative Disease Research: Opportunities and Translational Limitations.","authors":"Xiyue Yu, Qianqian Yao","doi":"10.2147/NDT.S614952","DOIUrl":"10.2147/NDT.S614952","url":null,"abstract":"<p><p>Neurodegenerative diseases including Alzheimer's disease and Parkinson's disease remain among the most challenging disorders to study, diagnose and treat. Despite rising prevalence with population aging, disease-modifying therapies remain scarce and research progress is hindered by biological complexity, patient heterogeneity, and incomplete experimental systems. Artificial intelligence (AI) has emerged as a transformative approach given the high-dimensional and multimodal data generated in this field. Traditional machine learning and deep learning have advanced imaging biomarker detection, disease trajectory prediction, drug target prioritization, and clinical data mining. More recently, foundation models and large language models (LLMs) have expanded AI from task-specific prediction tools to versatile assistants supporting literature retrieval, summarization, coding, data interpretation, and hypothesis generation. Although AI assistants promise to accelerate research workflows, their outputs are prone to dataset biases, poor interpretability, distribution shift, and hallucinations, which are particularly problematic in neurodegenerative research given subtle phenotypic variations, imperfect labeling, and protracted disease courses. This review evaluates the current applications of AI in neurodegenerative disease research, including drug discovery, biomarker identification, and multi-omics integration. We then discuss the transition from analytical AI models to general-purpose AI assistants and their potential to streamline scientific workflows. Critical limitations including bias, interpretability, reproducibility, and LLM hallucinations are highlighted, alongside ethical, regulatory and practical challenges. We argue that the most sustainable near-term model is human-AI collaboration rather than fully autonomous research, with its primary focus placed on research rather than clinical practice. Meaningful acceleration requires rigorous validation, transparent usage, and expert oversight to preserve scientific rigor and translational relevance.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"614952"},"PeriodicalIF":3.2,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13232534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caregiver Mental Health and Sociodemographic Factors Associated with the Burden of Care in Taiwan Among Primary Caregivers of Patients with Major Depressive Disorder: A Cross-Sectional Study.","authors":"Te-Chang Changchien, Yu-Wen Chiu, Tsung-Jen Hsieh, Yung-Chieh Yen, Ruey-Hsia Wang, Yu-Cheng Ho","doi":"10.2147/NDT.S606026","DOIUrl":"10.2147/NDT.S606026","url":null,"abstract":"<p><strong>Background: </strong>Caregivers of patients with major depressive disorder (MDD) frequently experience significant mental health and social burdens, yet evidence among Asian caregivers remains limited. This study aimed to identify factors associated with caregiver burden in the Taiwanese population.</p><p><strong>Methods: </strong>A cross-sectional survey of 150 caregiver-patient pairs was conducted in a psychiatric outpatient clinic in Taiwan. Caregiver burden, common mental symptoms, and depressive symptoms were assessed using validated instruments. Correlation and hierarchical regression analyses were performed to determine factors related to total and subdomain caregiver burden.</p><p><strong>Results: </strong>Caregivers reported a mild to moderate level of burden, with the highest index score in caregiver strain, and lowest in stigma. Both common mental symptoms and depressive symptoms were significantly correlated with total burden. Regression analyses showed that caregiver educational attainment and depressive symptoms were the strongest factors related to total burden, together explaining 43.7% of the variance. Depression severity also emerged as the key factor across several burden subdomains.</p><p><strong>Conclusion: </strong>Caregivers of MDD patients experience meaningful levels of burden, largely influenced by their mental health status, particularly depressive symptoms. These findings emphasize the need for targeted mental health assessment and supportive interventions to reduce caregiver burden and promote caregiver well-being.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"606026"},"PeriodicalIF":3.2,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-425-3p: A Promising Biomarker and Candidate for Pharmacological Intervention in Neuropsychiatric Disabilities with Relevance to Major Depressive Disorder.","authors":"Lloreal May, Yogesh Dwivedi","doi":"10.2147/NDT.S611548","DOIUrl":"10.2147/NDT.S611548","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Major depressive disorder (MDD) affects more than 280 million people worldwide and is one of the leading contributors to disability, premature mortality, and overall disease burden. Nearly 60% of individuals who die by suicide have an MDD diagnosis, underscoring its profound impact on both individuals and society. MDD arises from a complex interplay of genetic vulnerability, life experiences, and molecular alterations. Among these, epigenetic mechanisms have received particular attention because they help explain how environmental stress-especially chronic stress-can produce enduring biological changes. MicroRNAs (miRNAs) represent a key class of epigenetic regulators. These small, noncoding RNAs influence the efficiency with which target genes are translated into protein, thereby exerting potent post-transcriptional control over gene expression. Approximately 70% of known miRNAs are expressed in the brain, where they shape neuronal development, synaptic plasticity, and stress responsivity. Dysregulation of miRNA expression can disrupt coordinated gene networks and has been repeatedly associated with impairments in neurogenesis, neurotransmission, neuroinflammation, and endocrine signaling-processes central to the pathophysiology of MDD and other stress-related psychiatric conditions. Within this broader landscape, miR-425 has emerged as a particularly relevant epigenetic regulator across several brain disorders. Alterations in miR-425 expression have been reported in individuals with stress-related conditions and in animal models of chronic stress exposure. Emerging evidence suggests that miR-425 modulates several mood-relevant pathways, including regulation of the hypothalamic-pituitary-adrenal (HPA) axis, neuronal cell death, inflammatory signaling, and antidepressant treatment response as well as key signaling networks such as MAPK and Wnt. Given its regulatory role and disease-associated expression changes, miR-425 has gained significant interest as both a biomarker and a potential therapeutic target. In this review, we examine its biogenesis, molecular targets, and translational importance, positioning miR-425 as a promising candidate for psychiatric intervention strategies. A substantial knowledge gap remains and needs further study. For example, the functions of miR-425 within specific cell types and neural circuits are less defined, and most available evidence derives from rodent studies. Also, the support for miR-425 as a biomarker needs large, standardized, multisite, longitudinal studies integrating neuroimaging, proteomics, and detailed clinical phenotyping. In addition, we are only beginning to understand how pharmacologic and lifestyle interventions influence miR-425 expression. Finally, key downstream targets of miR-425 and safe, cell-type-specific delivery approaches for miR-425-based therapeutics remain underdeveloped. Collectively, these gaps underscore the need for rigorous, multimodal, translational research to determin","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"611548"},"PeriodicalIF":3.2,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-α-GPC in Cognitive Decline: Mechanisms and Clinical Evidence in Neurodegenerative Disorders.","authors":"Vannisa Artasya Putri, Raira Salsabila Hapsari, Riezki Amalia","doi":"10.2147/NDT.S579603","DOIUrl":"10.2147/NDT.S579603","url":null,"abstract":"<p><p>Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and vascular dementia are characterized by progressive neuronal loss, synaptic dysfunction, and cognitive decline. Despite the widespread use of symptomatic treatments, including acetylcholinesterase inhibitors and dopaminergic agents, these disorders remain incurable and lack disease-modifying therapies. L-α-Glycerylphosphorylcholine (L-α-GPC), a naturally occurring choline-containing phospholipid, has attracted interest for its dual roles as a precursor to acetylcholine biosynthesis and a modulator of neuroprotective signaling pathways. This narrative review summarizes current preclinical and clinical evidence regarding the mechanistic and clinical relevance of L-α-GPC in neurodegenerative disorders associated with cognitive impairment. Preclinical studies suggest that L-α-GPC can cross the blood-brain barrier, enhance cholinergic neurotransmission, upregulate neurotrophic factors such as brain-derived neurotrophic factor (BDNF), and modulate inflammatory responses, including those involving the α7 nicotinic acetylcholine receptor pathway. In animal models, L-α-GPC has been associated with improved cognitive performance, reduced neuroinflammation, and attenuation of amyloid-β and tau-related pathological features. Clinical studies have reported potential benefits of L-α-GPC, either as monotherapy or in combination with agents such as donepezil, in patients with AD, vascular dementia, mild cognitive impairment (MCI), and PD-related cognitive decline. However, the interpretation of these findings should be cautious because the available evidence remains heterogeneous, with notable variability in study design, dosage regimens, treatment duration, and outcome measures. Further well-designed, large-scale randomized controlled trials, together with biomarker-based assessments, are needed to clarify the therapeutic relevance and optimal clinical application of L-α-GPC in cognitive decline and neurodegenerative disorders. Overall, current evidence indicates that L-α-GPC may represent a promising adjunctive approach, although more robust validation is still required.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"579603"},"PeriodicalIF":3.2,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Fractalkine (FKN/CX3CL1) Pathway in Depression: A Critical Review of Its Role in Neuroinflammation and Therapeutic Potential.","authors":"ZhiLi YanLuan, Rula Sa, Yanting Fan, Huan Jia, Jianmiao Ge, Shuying Bai, RuiTing Ma, LiJun Tong","doi":"10.2147/NDT.S607481","DOIUrl":"10.2147/NDT.S607481","url":null,"abstract":"<p><p>Major Depressive Disorder (MDD), a global psychiatric disorder, involves complex pathogenesis in which neuroinflammation is considered one of the core pathophysiological processes. The fractalkine (FKN, CX3CL1)/CX3CR1 signaling pathway, a critical mediator of neuron-microglia communication, has been implicated in neuroinflammation and comorbid models depression, yet its precise and dynamic role in MDD remains controversial and insufficiently understood. This review aims to critically synthesize the existing literature to address these gaps. We first analyze the evidence for neuroinflammation in MDD, involving glial cells and pro-inflammatory cytokines. We then focus on the dual and context-dependent roles of the FKN/CX3CR1 pathway in regulating microglial function, synaptic plasticity, and inflammatory responses. Through a comparative analysis of existing literature, we suggest that neuroinflammation is a significant driver in the onset and progression of MDD, potentially engaging immune cells like microglia and astrocytes, and triggering the discharge of pro-inflammatory factors. The FKN/CX3CR1 pathway may play a dual role in regulating microglial function, maintaining synaptic homeostasis, and mediating inflammatory responses. Its dysregulation is potentially closely associated with inflammatory responses and synaptic damage in comorbid models, such as depression with diabetes and depression with rheumatoid arthritis. However, its specific role in MDD has not been fully elucidated, and direct evidence linking this pathway to major depressive disorder remains limited, as most current findings are derived from comorbid models or preclinical studies rather than clinical investigations. This review will systematically explore the general role of neuroinflammation in MDD, dissect the mechanisms of the FKN/CX3CR1 pathway in neuroinflammation and existing depression models, and prospectively potential therapeutic strategies and future research directions based on this pathway, thereby attempting to provide a new theoretical basis for the precision diagnosis and treatment of MDD.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"607481"},"PeriodicalIF":3.2,"publicationDate":"2026-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated with Poor Health-Related Quality of Life Among Patients with Epilepsy at Mulago National Referral Hospital.","authors":"Humphrey Atwijukiire, Juliana Namutundu, David Lubogo, Mark Kaddumukasa, Martha Sajatovic","doi":"10.2147/NDT.S604140","DOIUrl":"10.2147/NDT.S604140","url":null,"abstract":"<p><strong>Background: </strong>People with epilepsy (PWE) frequently experience reduced health-related quality of life (HRQOL) due to clinical, psychological, and social challenges. In Uganda, epilepsy is increasingly recognised as a public health issue; however, interventions have mainly focused on seizure control, with little attention to psychosocial determinants of well-being.</p><p><strong>Objective: </strong>To determine the frequency of poor HRQOL and associated factors among adult patients with epilepsy at Mulago National Referral Hospital (MNRH).</p><p><strong>Methods: </strong>We conducted a hospital-based cross-sectional study among adult PWE attending the mental health unit at MNRH. We enrolled participants using consecutive sampling. HRQOL was measured using the Quality of Life in Epilepsy Inventory (QOLIE-31). We defined Poor HRQOL as a score below the global mean score. We used modified Poisson regression with robust variance to estimate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for factors associated with poor HRQOL.</p><p><strong>Results: </strong>A total of 190 participants were included. The frequency of poor HRQOL was 50.53% (96/190). Poor HRQOL was independently associated with being married (aPR 1.37, 95% CI 1.02-1.85), primary education (aPR 2.01, 95% CI 1.27-3.16), secondary education (aPR 1.61, 95% CI 1.03-2.53), experiencing 6-10 seizures per year (aPR 1.53, 95% CI 1.08-2.17), borderline depressive symptoms (aPR 1.58, 95% CI 1.21-2.05), abnormal depressive symptoms (aPR 1.92, 95% CI 1.38-2.65), moderate stigma (aPR 4.07, 95% CI 1.75-9.43), and severe stigma (aPR 4.10, 95% CI 1.72-9.81). Self-employment was negatively associated with poor HRQOL (aPR 0.52, 95% CI 0.34-0.79).</p><p><strong>Conclusion: </strong>Poor HRQOL is common among adults with epilepsy receiving tertiary care in Uganda and is associated with seizure burden, depressive symptoms, stigma, and social characteristics. Integrating psychosocial screening for depression with HADS, stigma with SSE, and psychosocial support into routine epilepsy care may improve patient-centred outcomes.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"604140"},"PeriodicalIF":3.2,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}