Neuropsychiatric Disease and Treatment最新文献

{"title":"Functional Disability Among People with Schizophrenia in East Africa: A Systematic Review with Evidence Predominantly from Ethiopia.","authors":"Esterius Rabanus Ndunguru, Bives Mutume Nzanzu Vivalya, Charles Malisaba Posite, Comfort Ojochenemi Usman, Hussen Abdu Muhidin, Ismahil Adekunle Adeniyi, Ejike Daniel Eze, Ibe Michael Usman","doi":"10.2147/NDT.S653810","DOIUrl":"10.2147/NDT.S653810","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia causes substantial impairment in social, occupational, family, and everyday functioning. East African evidence is dispersed across disability scales, quality-of-life measures, employment outcomes, longitudinal studies, rehabilitation trials, and qualitative research. This review synthesized the magnitude, domains, correlates, measurement approaches, and rehabilitation evidence for functional disability among people with schizophrenia in East Africa.</p><p><strong>Methods: </strong>We conducted a PRISMA 2020 systematic review of studies involving people with schizophrenia in eight East African countries. Outcomes included disability, social and occupational functioning, activities of daily living, participation, functional recovery, and quality of life. We extracted study characteristics, outcomes, correlates, intervention findings, and qualitative themes, and assessed methodological quality using design-specific Joanna Briggs Institute checklists.</p><p><strong>Results: </strong>Fifteen publications from 2005 to 2025 were included; 14 (93.3%) were from Ethiopia and one (6.7%) from Rwanda, with no eligible publications identified from the other six prespecified East African countries. Cross-sectional studies predominated. Measures included WHOQOL-BREF, 36-item and 12-item WHODAS 2.0, SF-36, SOFAS, employment status, and qualitative approaches. Six publications had low risk-of-bias concern, eight had moderate concern, and one had high concern for causal or effect inference. Direct WHODAS evidence showed substantial disability, while longitudinal studies demonstrated persistent social and physical impairment. Negative symptoms, joblessness, prolonged untreated illness, substance use, weak social support, medication-related problems, and socioeconomic disadvantage were recurrent correlates. Community-based rehabilitation reduced disability in the cluster-randomized RISE trial. The available regional evidence is therefore heavily concentrated in Ethiopia.</p><p><strong>Conclusion: </strong>Functional impairment is multidimensional and extends beyond symptoms to work, social participation, daily activities, and quality of life. Integrated care should combine symptom management with rehabilitation, livelihood support, social inclusion, adherence support, and early treatment. Because the evidence is geographically concentrated in Ethiopia and uses heterogeneous measures, regional generalization should be cautious. Harmonized functional-outcome measurement and prospective multicountry research across East Africa are priorities.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"653810"},"PeriodicalIF":3.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220572","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":"Development and Internal Validation of an Inflammatory-Coagulation Biomarker-Enhanced Nomogram for 90-Day Outcome After Deep Hypertension-Related Intracerebral Hemorrhage.","authors":"Chongyao Lu, Zhitian Sheng, Xiaochuan Wei, Yu Shen, Xuehui Xiong, Lei Wang, Dayu Chen","doi":"10.2147/NDT.S643480","DOIUrl":"https://doi.org/10.2147/NDT.S643480","url":null,"abstract":"<p><strong>Background: </strong>Early prognostic assessment after intracerebral hemorrhage (ICH) relies mainly on neurological severity and neuroimaging features. Whether routinely available inflammatory-coagulation biomarkers provide meaningful incremental information beyond these established predictors remains uncertain.</p><p><strong>Objective: </strong>To develop and internally validate an admission-based nomogram incorporating inflammatory-coagulation biomarkers for predicting 90-day poor functional outcome in patients with deep hypertension-related ICH.</p><p><strong>Methods: </strong>This single-center retrospective cohort study included consecutive patients with deep hypertension-related ICH admitted between January 2020 and December 2025. Poor functional outcome was defined as a 90-day modified Rankin Scale score of 4-6. Candidate predictors available within 24 hours of admission were evaluated using least absolute shrinkage and selection operator logistic regression followed by multivariable logistic regression. Model performance was assessed using discrimination, calibration, Brier score, bootstrap internal validation, reclassification metrics, and decision curve analysis.</p><p><strong>Results: </strong>Among 462 patients, 162 (35.1%) had poor functional outcome. The final model retained age, Glasgow Coma Scale score, hematoma volume, intraventricular hemorrhage, admission blood glucose, neutrophil-to-lymphocyte ratio, and ln(D-dimer). Adding NLR and ln(D-dimer) increased the AUC from 0.765 to 0.828 (P = 0.008), representing a statistically significant but modest absolute improvement of 0.063, and reduced the Brier score from 0.178 to 0.142. The optimism-corrected AUC was 0.816. Decision curve analysis showed greater net benefit than the conventional model across threshold probabilities of 15%-65%. Sensitivity analyses yielded consistent biomarker associations and model performance.</p><p><strong>Conclusion: </strong>Adding NLR and D-dimer to established clinical-imaging predictors provided a modest improvement in 90-day outcome prediction in deep hypertension-related ICH. These biomarkers may offer complementary prognostic information, but the clinical importance of this incremental gain remains to be established. External validation is required before broader clinical application.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"643480"},"PeriodicalIF":3.2,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195740","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":"Ketogenic Diet and Neurological Health: A Narrative Review with Natural Language Processing-Assisted Thematic Mapping Using BERTopic.","authors":"Benneng Jin, Zhe Chen, Ruijin Xie, Yueying Liu","doi":"10.2147/NDT.S627639","DOIUrl":"https://doi.org/10.2147/NDT.S627639","url":null,"abstract":"<p><strong>Background: </strong>The ketogenic diet (KD) is an established therapy for drug-resistant epilepsy and is increasingly investigated across other neurological disorders.</p><p><strong>Objective: </strong>To provide an updated narrative synthesis of recent mechanistic and clinical evidence on KD across neurological disorders, including its therapeutic applications, potential mechanisms, and current evidence gaps, and to use BERTopic as a supplementary natural language processing tool to characterize major research themes and temporal changes in research emphasis.</p><p><strong>Methods: </strong>Literature published from 2021 to early 2026 was retrieved from Scopus, Web of Science, and PubMed. After deduplication and eligibility screening, 1017 records were included in BERTopic analysis. PubMedBERT, UMAP, HDBSCAN, and c-TF-IDF were used for thematic mapping; interpretation and evidence synthesis remained expert-guided. Temporal analyses were restricted to 2021-2025.</p><p><strong>Results: </strong>Seven thematic clusters were retained, with increased representation of gut-brain-axis-related publications after 2023. Narrative synthesis highlighted energy metabolism, mitochondrial function, oxidative stress, neuroinflammation, neurotransmitter regulation, and the gut-brain axis as major mechanistic domains. Clinical evidence was strongest for drug-resistant epilepsy, while findings for Alzheimer's disease and migraine were less mature and those for Parkinson's disease remained preliminary.</p><p><strong>Conclusion: </strong>KD is an established therapy for drug-resistant epilepsy and shows potential across other neurological disorders, particularly Alzheimer's disease and migraine. Its effects may involve energy metabolism, mitochondrial function, oxidative stress, neuroinflammation, neurotransmitter regulation, and the gut-brain axis. BERTopic-assisted mapping complemented the narrative synthesis by summarizing major research themes and temporal trends.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"627639"},"PeriodicalIF":3.2,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195700","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":"Ketamine and Esketamine in Acute Suicidal Presentations: Evidence, Limits, and a Conceptual Recovery-Enabling Downstaging Framework.","authors":"Anita Słupska, Wiesław Jerzy Cubała, Damian Świeczkowski, Joanna Szarmach, Adam Włodarczyk, Jakub Słupski","doi":"10.2147/NDT.S641718","DOIUrl":"https://doi.org/10.2147/NDT.S641718","url":null,"abstract":"<p><strong>Objective: </strong>To synthesize evidence for intravenous racemic ketamine and regulated intranasal esketamine in adults with acute suicidal presentations; distinguish the outcomes these interventions have and have not been shown to change; and place any rapid response within a complete emergency suicide-care pathway.</p><p><strong>Methods: </strong>A narrative review of PubMed/MEDLINE-indexed literature was updated through July 16, 2026. Searches and study selection were performed by Wiesław Jerzy Cubała and Anita Słupska. Priority was given to randomized trials, systematic reviews and meta-analyses, pivotal ASPIRE publications, current US and European product information, and studies of emergency-department safety planning, lethal-means counseling, and post-discharge care. No formal risk-of-bias assessment or pooled reanalysis was undertaken.</p><p><strong>Results: </strong>Intravenous racemic ketamine has randomized and meta-analytic evidence for rapid, short-term reduction of suicidal ideation in selected adults, with important variation by population, comparator, measure, and follow-up. The evidence does not establish prevention of suicide attempts or deaths. In ASPIRE I and II, regulated intranasal esketamine added to hospitalization, a newly initiated or optimized oral antidepressant, and comprehensive standard care accelerated improvement in depressive symptoms; clinician-rated suicidality improved markedly in both groups and did not consistently separate from placebo plus standard care. Across both evidence streams, a post-dose score cannot substitute for dynamic risk formulation, level-of-care decisions, safety planning, lethal-means restriction, or a confirmed transition of care.</p><p><strong>Conclusions: </strong>Intravenous racemic ketamine may produce a rapid, short-term reduction in suicidal ideation in selected adults, whereas regulated intranasal esketamine has demonstrated accelerated improvement in depressive symptoms in hospitalized patients with major depressive disorder and acute suicidal ideation with intent, without a consistent treatment-specific effect on suicidality. Neither intervention has been shown to prevent suicide attempts or deaths. We propose a conceptual, non-validated recovery-enabling downstaging framework to describe a time-limited movement from high acuity toward a state in which collaboration and definitive treatment become more feasible. The framework is intended to complement, not replace, dynamic risk formulation, safety planning, and disposition assessment.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"641718"},"PeriodicalIF":3.2,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195751","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":"Advances in the Antidepressant Effects of Electroacupuncture Through Regulation of Microglia-Mediated BDNF Signaling and Hippocampal Neurogenesis.","authors":"Hong Liu, Jiapeng Wang, Qinyuan Yang, Zaixiang Zhang, Zeng Peng, Xia Lei, Yichun Zhao, Deping Zhao, Jianxiong Gu","doi":"10.2147/NDT.S636227","DOIUrl":"https://doi.org/10.2147/NDT.S636227","url":null,"abstract":"<p><strong>Objective: </strong>To summarize the regulatory network linking microglia, brain-derived neurotrophic factor (BDNF) signaling, and hippocampal neurogenesis, and to clarify the potential antidepressant mechanisms of electroacupuncture.</p><p><strong>Methods: </strong>We systematically reviewed and integrated recent findings from preclinical and clinical studies regarding microglial activation, BDNF/tropomyosin receptor kinase B (TrkB) signaling, hippocampal neurogenesis, and electroacupuncture intervention in depressive disorders, retrieved from PubMed, Web of Science, and CNKI databases up to June 2026.</p><p><strong>Results: </strong>Depression is closely associated with neuroinflammation, impaired neuroplasticity, and disrupted hippocampal neurogenesis. Aberrant microglial activation may inhibit hippocampal neurogenesis by releasing pro-inflammatory cytokines, excessively engulfing synapses, and disturbing the neural microenvironment. These pathological changes interact with dysregulated BDNF/TrkB signaling and jointly contribute to depressive phenotypes. Electroacupuncture may exert antidepressant effects by modulating microglial phenotypic transformation, suppressing pro-inflammatory mediator release, and upregulating BDNF/TrkB signaling and its downstream pathways.</p><p><strong>Conclusion: </strong>Electroacupuncture may improve depression through coordinated regulation of microglia-mediated neuroinflammation and BDNF-related neuroplasticity. This mechanism provides a scientific basis for further mechanistic research and clinical application of acupuncture in depression.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"636227"},"PeriodicalIF":3.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183409","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":"Treatment Goals in Schizophrenia as Seen by Matched Patients and Physicians: Preferences and Medication Formulation Strategies.","authors":"Bernhard T Baune, Wolfgang Janetzky","doi":"10.2147/NDT.S640272","DOIUrl":"https://doi.org/10.2147/NDT.S640272","url":null,"abstract":"<p><strong>Background: </strong>In the treatment of schizophrenia, it is important that physicians and patients discuss treatment goals and measures to reach these, including medication formulations (oral or long-acting injectable, LAI).</p><p><strong>Methods: </strong>A survey was conducted in matched pairs of patients with schizophrenia and their treating psychiatrists. The questionnaires contained treatment goals that were rated by the participants, along with questions about oral and LAI medication. Study objectives were to rank treatment goals from a patient's and psychiatrist's perspective, assess the psychiatrist's and patient's choice of oral antipsychotic vs LAI to reach the goals, and assess concordance of treatment goals and treatment choice between psychiatrists and patients.</p><p><strong>Results: </strong>Responses from 43 physician-patient pairs involving 14 individual physicians (0.9% of contacted physicians) were received. Treatment goals were rated equally for a large proportion (39-71%) of physician-patient pairs in the goal categories \"effectiveness/symptom reduction\" and \"quality of life/functioning/participation\", but less so for the category \"tolerability\" (30-56%), which appeared more important to patients. The majority of surveyed patients preferred oral medication, while physicians tended to perceive oral and LAI medication as equally suitable. Conversations about LAIs were more frequent if patients had already tried LAI.</p><p><strong>Conclusions: </strong>Patients tended to have a stronger focus on avoiding side effects than their physicians and seemed to prefer oral medication to reach their goals. Our results come from a small convenience sample with low response rate and should be interpreted as exploratory. Still, there may be room for improvement of physician-patient conversations.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"640272"},"PeriodicalIF":3.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183371","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":"Association Between Tctex1 Domain Containing 1 Expression and Major Depressive Disorder.","authors":"Chien-Yuan Chen, Tiao-Lai Huang","doi":"10.2147/NDT.S636450","DOIUrl":"https://doi.org/10.2147/NDT.S636450","url":null,"abstract":"<p><strong>Introduction: </strong>Major depressive disorder (MDD) involves peripheral immune-inflammatory dysregulation. Tctex1 Domain Containing 1 (TCTEX1D1), a dynein light chain expressed predominantly in monocytes among circulating immune cells, was recently nominated as a candidate risk gene for MDD by brain-derived transcriptome-wide association studies, but its peripheral mRNA expression in MDD has not been examined. We aimed to quantify TCTEX1D1 mRNA in peripheral blood mononuclear cells (PBMCs) of acute-phase MDD patients and to track its trajectory over four weeks of antidepressant treatment.</p><p><strong>Methods: </strong>We recruited 154 participants, comprising 89 drug-free patients with acute-phase MDD and 65 healthy controls; 78 patients completed paired four-week antidepressant follow-up. MDD was diagnosed according to DSM-5 criteria, depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAM-D), and treatment response was defined as a ≥50% HAM-D reduction. TCTEX1D1 mRNA in PBMCs was quantified by qRT-PCR. Group differences were tested by analysis of covariance on ΔCt adjusted for age, body mass index (BMI), and sex, with sensitivity analyses for age; longitudinal change was analyzed by linear mixed-effects modeling.</p><p><strong>Results: </strong>TCTEX1D1 mRNA was significantly lower in MDD patients than in healthy controls (fold-change ratio 0.32, p < 0.001), and the effect persisted across sensitivity analyses for age. No disease × sex interaction was observed (p = 0.568). In female patients, TCTEX1D1 showed only modest diagnostic discrimination (ROC AUC 0.68). Overall TCTEX1D1 levels did not change over four weeks (p = 0.760); an exploratory comparison of responders and non-responders showed only an unconfirmed signal, possibly reflecting regression to the mean.</p><p><strong>Conclusion: </strong>PBMC TCTEX1D1 mRNA is significantly downregulated in acute-phase MDD. This is the first peripheral-blood evidence for this brain-nominated candidate gene. TCTEX1D1 is best positioned as a disease-state marker rather than a stand-alone diagnostic. Replication in larger cohorts is needed, and the longitudinal findings remain exploratory and hypothesis-generating.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"636450"},"PeriodicalIF":3.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183391","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":"Untargeted Urinary Metabolomic Profiling Reveals Metabolic Signatures Associated with Anhedonia Severity-Stratified Subgroups in Major Depressive Disorder.","authors":"Shoucui Xia, Jun Cheng, Guoqing Gao, Qingqing Zhao, Wenzhi Pei, Long Chen, Xulai Zhang","doi":"10.2147/NDT.S647919","DOIUrl":"https://doi.org/10.2147/NDT.S647919","url":null,"abstract":"<p><strong>Objective: </strong>To investigate urinary metabolite differences between subgroups stratified by anhedonia severity in patients with major depressive disorder (MDD) and identify potential biomarkers associated with anhedonia using untargeted metabolomic profiling.</p><p><strong>Methods: </strong>Fifty-five MDD patients were recruited and stratified by median Snaith-Hamilton Pleasure Scale (SHAPS) total score into Low-SHAPS (n=32) and High-SHAPS (n=23) groups, along with 35 healthy controls (HC). Urinary metabolomic profiling was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differential metabolites were identified using one-way ANOVA for multi-group comparisons and independent-sample <i>t</i>-tests for pairwise comparisons, followed by multivariate statistical analyses and pathway enrichment analysis.</p><p><strong>Results: </strong>Three-group ANOVA identified 706 nominally differential metabolites (P < 0.05), of which 115 reached P < 0.01. The contrast between Low-SHAPS and High-SHAPS groups showed the most pronounced differences, with 1608 metabolites reaching nominal significance (P < 0.05). OPLS-DA models demonstrated significant discriminative ability across all pairwise comparisons after permutation testing (Low vs High: cross-validated AUC = 0.726, P = 0.010; Low vs HC: cross-validated AUC = 0.886, P = 0.010; High vs HC: cross-validated AUC = 0.901, P = 0.010). Pathway enrichment analysis revealed significant alterations in tryptophan metabolism and phenylalanine metabolism.</p><p><strong>Conclusions: </strong>MDD patients with differing degrees of anhedonia exhibit widespread urinary metabolic differences. The greater metabolic divergence between High-SHAPS and Low-SHAPS subgroups compared with patient-control comparisons suggests that anhedonia contributes substantially to metabolic heterogeneity in depression. SHAPS-based stratification offers novel metabolomic evidence for precision subtyping and biomarker discovery.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"647919"},"PeriodicalIF":3.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168577","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":"Allostatic Load and Severe Clinical Phenotypes in Major Depressive Disorder: A Cross-Sectional Statistical Mediation Analysis of Perceived Stress, Cognitive Impairment, and Suicidal Ideation.","authors":"Shuo Wang, Wenhui Ren, Pengfei Yun, Yueying Lu, Na Li","doi":"10.2147/NDT.S631554","DOIUrl":"https://doi.org/10.2147/NDT.S631554","url":null,"abstract":"<p><strong>Background: </strong>Perceived stress is associated with adverse clinical features of major depressive disorder (MDD), but the role of multisystem physiological dysregulation remains uncertain. We examined whether allostatic load (AL) was statistically associated with the relationship between perceived stress and cognitive impairment or severe suicidal ideation.</p><p><strong>Methods: </strong>This retrospective, cross-sectional electronic medical record study included 385 adults with DSM-5 MDD assessed within a single three-day index window. Perceived stress was measured with the 14-item Perceived Stress Scale (PSS-14), and chronic exposure context was characterized from documented negative life events. AL was calculated from 15 cardiovascular, metabolic, immune-inflammatory, and neuroendocrine indicators. Cognitive impairment was defined as Montreal Cognitive Assessment (MoCA) <26 and severe suicidal ideation as Columbia-Suicide Severity Rating Scale (C-SSRS) ideation severity ≥4. Sequential logistic regression and bootstrap product-of-coefficients statistical mediation analyses were performed.</p><p><strong>Results: </strong>Compared with Low AL, High AL was associated with cognitive impairment (adjusted odds ratio [aOR] 6.17, 95% CI 2.89-13.15) and severe suicidal ideation (aOR 6.43, 95% CI 2.98-13.88; both P<0.001). Continuous AL showed consistent associations with both outcomes. The indirect effect through AL was supported for cognitive impairment (0.39, 95% bootstrap CI 0.16-0.69), but not for severe suicidal ideation (0.14, 95% bootstrap CI -0.12 to 0.41).</p><p><strong>Conclusion: </strong>Higher AL was independently associated with both adverse clinical phenotypes. Statistical mediation was supported for the perceived stress-cognitive impairment association but not for suicidal ideation. Because exposure, mediator, and outcomes were assessed within the same index window, temporal and causal mediation cannot be inferred.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"631554"},"PeriodicalIF":3.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167270","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-Reported Behavioral Changes After Donepezil Transdermal Patch Therapy in Alzheimer's Disease: An Exploratory Real-World Network Analysis.","authors":"Tomokazu Shimazu, Eri Hoshino, Maki Nakaseko, Kanako Homma, Satoshi Suzuki, Kei Horikoshi, Yuichi Maruki","doi":"10.2147/NDT.S637015","DOIUrl":"https://doi.org/10.2147/NDT.S637015","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize caregiver-reported behavioral changes after donepezil transdermal patch therapy and to examine the descriptive connectivity of co-occurring improvements in patients with Alzheimer's disease (AD).</p><p><strong>Patients and methods: </strong>This retrospective, single-center observational study included 26 patients meeting the 2011 National Institute on Aging-Alzheimer's Association criteria for probable AD dementia. Approximately 2-4 months after patch initiation, caregivers rated nine behavioral domains using routine, non-validated single-item change assessments as improved, unchanged, or worsened relative to the pre-treatment state. A descriptive co-improvement network was used solely to summarize pairwise co-occurrence of binary improvement indicators using phi-coefficients and observed strength centrality. Because of the small sample and sparse binary events, all network measures were treated as sample-specific descriptive quantities rather than inferential estimates.</p><p><strong>Results: </strong>The most frequently improved domains were smiling/positive affect (12/26, 46.2%), calmness (9/26, 34.6%), and night-time sleep (8/26, 30.8%). Calmness had the highest observed strength centrality (2.467), followed by grooming behavior (2.059), hobbies/interests (2.009), and housework/instrumental activities of daily living (1.938). Calmness remained the highest-strength node in all 26 leave-one-participant-out sensitivity analyses. No treatment discontinuations or serious adverse events were documented.</p><p><strong>Conclusion: </strong>Caregiver-perceived calmness, assessed as a single non-validated change item, was the most highly connected domain in this small descriptive co-improvement network. The findings are exploratory and do not establish treatment efficacy, a validated agitation-related outcome, temporal direction, or mechanism. Prospective studies using standardized behavioral measures are needed.</p>","PeriodicalId":19378,"journal":{"name":"Neuropsychiatric Disease and Treatment","volume":"22 ","pages":"637015"},"PeriodicalIF":3.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168570","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}