Brain disorders (Amsterdam, Netherlands)最新文献

{"title":"Genetic characterisation of ATXN2 in Australian amyotrophic lateral sclerosis","authors":"Sharlynn S.L. Wu ,&nbsp;Emily P. McCann ,&nbsp;Sandrine Chan Moi Fat ,&nbsp;Natalie Grima ,&nbsp;Lyndal Henden ,&nbsp;Liam G. Fearnley ,&nbsp;Patrick Chiu ,&nbsp;Kelly L. Williams ,&nbsp;Dominic B. Rowe ,&nbsp;Garth A. Nicholson ,&nbsp;Matthew C. Kiernan ,&nbsp;Ian P. Blair ,&nbsp;Shu Yang ,&nbsp;Jennifer A. Fifita","doi":"10.1016/j.dscb.2025.100301","DOIUrl":"10.1016/j.dscb.2025.100301","url":null,"abstract":"<div><div>Large expansions of a trinucleotide repeat encoding a polyglutamine tract in <em>ATXN2</em> are a known cause of spinocerebellar ataxia 2, and intermediate length expansions in this gene have been reported as a risk factor and phenotypic modifier for amyotrophic lateral sclerosis (ALS). Here we present a comprehensive analysis of the genetic contribution of <em>ATXN2</em> to ALS within an Australian cohort of 821 ALS cases. We performed association for both disease status and ALS clinical phenotypes, with careful consideration of repeat size and composition, and the presence of additional genetic variants within <em>ATXN2</em>. The largest expansion detected among cases was 33 repeat units, and 32 in controls, while the most common repeat size was 22. Intermediate expansions of 30–33 repeats were significantly more common in ALS cases (1.95 %) than controls (0.42 %, <em>p</em> = 0.02543), and we found this association to be primarily driven by familial rather than sporadic ALS cases (frequency of 4.30 % vs 1.65 % and <em>p</em> = 0.00790 vs 0.05799). All intermediate expansions in ALS cases harboured at least one CAA synonymous interruption. No association was found between intermediate expansions and site or age of disease onset, or disease duration. However, larger intermediate repeat sizes of 32–33 repeats were associated with a shorter disease duration (median=27.35 months) when compared with cases who harboured an <em>ATXN2</em> repeat size in the normal range (median=35.47 months, <em>p</em> = 1.89 × 10^–6). These findings indicate that intermediately expanded <em>ATXN2</em> repeats may play an important gene modifier role in Australian ALS cohorts.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100301"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum regarding previously published article","authors":"","doi":"10.1016/j.dscb.2026.100307","DOIUrl":"10.1016/j.dscb.2026.100307","url":null,"abstract":"","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100307"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147538440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-Cas9 gene editing in neuropsychiatric disorders: Challenges and promising avenues","authors":"Nicholas Aderinto ,&nbsp;Gbolahan Olatunji ,&nbsp;Emmanuel Kokori ,&nbsp;Ismaila Ajayi Yusuf ,&nbsp;Moradeyo Abdulrahmon ,&nbsp;Emmanuel Egbunu ,&nbsp;Temiloluwa Oluwakorede Adefusi ,&nbsp;Opabode Mountain Obasanjo ,&nbsp;John Aboje ,&nbsp;Ikponmwosa Jude Ogieuhi ,&nbsp;Oluwatobiloba Oluwatomisin Apampa","doi":"10.1016/j.dscb.2025.100304","DOIUrl":"10.1016/j.dscb.2025.100304","url":null,"abstract":"<div><div>This review explores the transformative potential of CRISPR-Cas9 gene editing technology in neuropsychiatric disorders. Neuropsychiatric conditions, marked by genetic and environmental factors, pose significant global health challenges. Traditional treatments often address symptoms, leaving underlying genetic anomalies untouched. CRISPR-Cas9, renowned for its unparalleled precision, presents an opportunity to unravel the complex genetic architecture contributing to disorders like schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). The review explores specific applications of CRISPR technology, showcasing studies targeting genes associated with these disorders and exploring alternative splicing mechanisms, microexon involvement, and the role of master regulators. Despite the revolutionary promise of CRISPR, challenges and limitations must be addressed. Technical challenges, such as achieving allele-specific modifications and minimising off-target effects, require ongoing research. Safety concerns, ethical considerations regarding germline editing, and potential unintended consequences emphasise the need for cautious implementation. Ongoing research aims to refine CRISPR techniques, enhance precision, and overcome current challenges. Collaboration between scientists, ethicists, clinicians, and patient advocacy groups is pivotal for responsible implementation. Identifying specific genes or pathways for therapeutic targeting holds promise for personalised and precise interventions. This review envisions a future where the responsible integration of CRISPR technology transforms the understanding and treatment of neuropsychiatric disorders, providing a multidimensional approach that balances scientific innovation with ethical considerations.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100304"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145737014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the predictive value of vomiting versus physical examination for a CT scan in children with head injury","authors":"Ali Tarabeih ,&nbsp;Karine Beiruti Wiegler ,&nbsp;Bian Abu Salah ,&nbsp;Doua Bakry","doi":"10.1016/j.dscb.2026.100311","DOIUrl":"10.1016/j.dscb.2026.100311","url":null,"abstract":"<div><h3>Background</h3><div>Head injuries are common in children of all ages. While most are minor and do not require intervention, severe cases remain a leading cause of mortality and disability. Identifying minor head trauma with a significant risk of intracranial injury is challenging. Vomiting is a frequent symptom after pediatric head injury, but its predictive value for intracranial pathology remains uncertain. This study investigates the relationship between vomiting and pathological CT findings in children with head injury.</div></div><div><h3>Methods</h3><div>We conducted a retrospective single-center study of 655 children aged 1-18 with minor head injuries who presented to the pediatric emergency department (2019-2021). Physical examination abnormalities were analyzed as a composite variable. Logistic regression identified predictors of pathological CT findings among children with vomiting.</div></div><div><h3>Results</h3><div>Vomiting occurred in 30.9% of patients. CT rates and pathological findings were similar between children with vomiting (41.1% scanned, 22.9% with pathology) and those without vomiting (38.6% scanned, 21.1% with pathology). Among children with vomiting who underwent CT, composite physical examination abnormalities predicted pathological findings (OR=14.2, 95% CI: 1.75–114.68). However, these variable combined heterogeneous findings from minor scalp hematomas to neurological deficits, limiting interpretation.</div></div><div><h3>Conclusions</h3><div>Vomiting alone was not associated with increased pathological CT findings. Composite physical examination abnormalities predicted CT pathology in children with vomiting. Major limitations include the composite nature of the variable, lack of CT or follow-up in 60.5% of patients, incomplete vomiting data, and selection bias in imaging. Prospective studies with validated criteria and systematic follow-up are needed to confirm observation safety.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100311"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147421368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of the serum metabolome and gut microbiome underscores the importance of altered lipid metabolism and potential immune modulation in Parkinson's Disease","authors":"Keren Zhang ,&nbsp;Kimberly C Paul ,&nbsp;Jonathan P Jacobs ,&nbsp;Yuyuan Lin ,&nbsp;Dayoon Kwon ,&nbsp;Roch Nianogo ,&nbsp;Jeff M Bronstein ,&nbsp;Adrienne M Keener ,&nbsp;Yu Yu ,&nbsp;Aline Duarte Folle ,&nbsp;Dean P Jones ,&nbsp;Beate Ritz","doi":"10.1016/j.dscb.2026.100310","DOIUrl":"10.1016/j.dscb.2026.100310","url":null,"abstract":"<div><h3>Introduction</h3><div>Single-omics studies have deepened our understanding of disease-related molecular processes, though integrated approaches are needed to uncover cross-system interactions. We previously reported changes in the serum metabolome and gut microbiome in Parkinson’s disease (PD). To build on these findings, we conducted a multi-omics integration analysis to examine the interplay between the gut microbiome and human metabolism in PD.</div></div><div><h3>Methods</h3><div>In a community-based study of 113 PD patients from rural California, microbiome profiles were obtained via 16S rRNA gene sequencing of fecal samples. Serum metabolomic profiles were generated using untargeted high-resolution LC-MS. Residual matrices of metabolomics data were extracted after adjusting for age, sex, racial minority status, and study wave. We identified PD-associated bacterial genera and summarized their abundance using principal component analysis. Using this summary score as the dependent variable, we performed partial least squares (PLS) regression to identify serum metabolites associated with the PD-related gut microbiome. Pathway enrichment analysis was then conducted on selected metabolite features from the PLS model.</div></div><div><h3>Results</h3><div>We identified 266 metabolite features and annotated 29 metabolic compounds associated with PD-related microbes (<em>p</em> &lt; 0.1). Enrichment analysis revealed perturbed pathways in lipid metabolism, including fatty acid activation and metabolism, linoleate metabolism, and glycerophospholipid metabolism, as well as carbohydrate metabolism such as hexose phosphorylation and starch/sucrose metabolism.</div></div><div><h3>Conclusion</h3><div>Our multi-omics integration analysis revealed that PD-associated gut microbiota are involved in host lipid metabolism, immune-related pathways, and potentially vitamin B-mediated regulation of kynurenine pathway metabolism, providing insights into potential microbiome–metabolome interactions in PD pathophysiology.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100310"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147421366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Blood brain-derived neurotrophic factor levels in patients with sequelae of carbon-monoxide poisoning 60 years after a coal-dust explosion: A cross-sectional study” Brain Disorders 19 (2025) 100264","authors":"Eriko Baba ,&nbsp;Ryuki Hashida ,&nbsp;Yoshio Takano ,&nbsp;Yuji Maki ,&nbsp;Hiroshi Tajima ,&nbsp;Makiko Motooka ,&nbsp;Hiromichi Motooka ,&nbsp;Hiroo Matsuse","doi":"10.1016/j.dscb.2026.100309","DOIUrl":"10.1016/j.dscb.2026.100309","url":null,"abstract":"","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"21 ","pages":"Article 100309"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147538439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five-Year Longitudinal Trajectories of Non-Motor Symptoms in Relation to Baseline Dopaminergic Decline in Parkinson’s Disease","authors":"Mehrdad Mozafar ,&nbsp;Hanieh Mirhosseini ,&nbsp;Setayesh Farahani ,&nbsp;Hamid Harandi ,&nbsp;Setareh Garousi ,&nbsp;Fatemeh Samadian ,&nbsp;Ali Rezaei ,&nbsp;Hossein Hamidi ,&nbsp;Melika Jameie ,&nbsp;Samira Rezaei ,&nbsp;Mehran Mottahedi ,&nbsp;Mahsa Mayeli","doi":"10.1016/j.dscb.2025.100288","DOIUrl":"10.1016/j.dscb.2025.100288","url":null,"abstract":"<div><h3>Introduction</h3><div>While Non-motor symptoms (NMS) in Parkinson’s disease (PD) substantially affect quality of life, their association with dopaminergic dysfunction remains unclear. This study examined longitudinal associations between NMS and striatal dopamine transporter single-photon emission computed tomography (DaT-SPECT) measures over five years in PD patients.</div></div><div><h3>Methods</h3><div>We studied 258 PD patients from the Parkinson’s Progression Markers Initiative (PPMI). The associations between the baseline DaT-SPECT-derived specific binding ratios (SBR) in the caudate, putamen, and striatum and longitudinal NMS, including rapid eye movement sleep behavior disorder (RBD), Epworth Sleepiness Scale, impulsivity, depression, anxiety, cognition, and olfaction were investigated.</div></div><div><h3>Results</h3><div>Greater caudate SBR asymmetry at baseline was associated with poorer visuospatial reasoning at year 2 (<em>p</em> &lt; 0.001). Lower initial putamen and striatal SBR correlated with impaired verbal memory retention at year 3 (<em>p</em> &lt; 0.001). Reduced baseline bilateral putamen SBR were linked to deficits in working memory and executive function at year 4 (<em>p</em> &lt; 0.001). Decreased baseline putamen uptake was associated with higher anxiety five years after diagnosis (<em>p</em> &lt; 0.001). Lower baseline caudate and striatal uptake was noted in PD patients who manifested depression 4–5 years later, whereas diminished baseline caudate, putamen, and striatal SBR was detected in those who exhibited RBD five years post-diagnosis (<em>p</em> &lt; 0.05). Predictive modeling indicated modest diagnostic accuracy, with olfactory dysfunction best distinguished using the asymmetry index (AUC &gt; 0.6).</div></div><div><h3>Conclusion</h3><div>Reduced striatal dopamine uptake, particularly in the caudate and putamen, was associated with progression of NMS including anxiety, depression, memory loss, visuospatial impairment, and RBD. Baseline DaT-SPECT may serve as a useful tool for anticipating NMS trajectories in PD.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"20 ","pages":"Article 100288"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host and microbiota interaction in depression syndrome","authors":"Zeinab Mohsenipour ,&nbsp;Pariya Keshavarz ,&nbsp;Zahra Shahpasand Moghanloo","doi":"10.1016/j.dscb.2025.100291","DOIUrl":"10.1016/j.dscb.2025.100291","url":null,"abstract":"<div><div>Depression is a multifactorial mental disorder with genetic, environmental, and neurobiological influences. More recently, the role of the gut microbiota in the pathophysiology of depression has received growing interest, placing the gut-brain axis as a key mediator in this relationship. Dysbiosis, or an imbalance in the gut microbial community, may correlate with neurotransmitter synthesis alteration, immune demodulation, and increased inflammation—all of which contribute to depressive symptoms. The current review discusses the growing evidence that supports the involvement of the gut microbiota in depression by focusing on its mechanisms of action, including microbial-driven neuroinflammation, as well as alterations in the production of 5-HT and γ-aminobutyric acid (GABA) and the modulation of the immune system. We also discuss interventions, including Fecal microbiota transplant (FMT) and dietary supplements, in an attempt to bring the gut microbiota to a healthy state and improve depressive symptoms. However, several challenges remain in translating microbiome-based therapies into clinical practice. Future research should focus on elucidating the exact microbial species involved, identifying biomarkers for targeted therapies, and conducting large-scale clinical trials to assess the long-term efficacy and safety of microbiome modulation as a treatment for depression.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"20 ","pages":"Article 100291"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case series of infantile epileptic spasms syndrome: diagnosis, treatment choices and genetic landscape","authors":"C. Tsimakidi,&nbsp;M. Gontika,&nbsp;St. Giamouri,&nbsp;N. Kallias,&nbsp;C. Kotsalis,&nbsp;F. Mylona,&nbsp;D. Gkougka","doi":"10.1016/j.dscb.2025.100280","DOIUrl":"10.1016/j.dscb.2025.100280","url":null,"abstract":"<div><h3>Objective</h3><div>We present a one‑year case series of nine patients diagnosed with Infantile Epileptic Spasms Syndrome (IESS) treated in our clinic.</div></div><div><h3>Methods</h3><div>Nine (9) patients presenting with spasms underwent electroencephalogram (EEG) which confirmed the diagnosis of IESS in all cases. Their clinical presentation, EEG, MRI and genetic findings are reviewed.</div></div><div><h3>Results</h3><div>Hypsarrhythmia and spasms resolved in all patients. However developmental outcomes as psychomotor delay (4/9) and autism (3/9) and the progression to other types of epilepsy (6/9) remain under evaluation. Genetic and imaging findings are provided.</div></div><div><h3>Conclusion</h3><div>IESS encompasses a spectrum of underlying aetiologies and continues to pose therapeutic challenges. While aggressive treatment is necessary in the acute phase, long-term psychomotor outcomes depend on aetiology and remain largely unpredictable. Genetic testing plays a key role in clarifying underlying causes and informing prognosis.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"20 ","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating zuranolone: Discrepancies and insights from multiple systematic reviews and meta-analyses on major depression and postpartum depression treatment","authors":"Abdulqadir J. Nashwan ,&nbsp;Areesha Jawed","doi":"10.1016/j.dscb.2025.100293","DOIUrl":"10.1016/j.dscb.2025.100293","url":null,"abstract":"<div><div>Zuranolone, a novel neuroactive steroid and positive allosteric modulator of γ-aminobutyric acid type A (GABA_A) receptors, has been explored for its potential in treating major depressive disorder (MDD) and postpartum depression (PPD). This review compiles findings from multiple systematic reviews and meta-analyses, emphasizing its rapid action and efficacy in alleviating depressive symptoms. Significant improvement is consistently observed by day 15 of treatment, positioning zuranolone as a promising option for rapid relief in depressive episodes. However, variability in research outcomes and methodology across different studies highlights the complexity of evaluating new treatments. Safety concerns, particularly at higher doses, and the increased incidence of side effects such as dizziness and somnolence, call for cautious dose management and close monitoring. Cultural and regional differences also influence treatment efficacy, suggesting the need for culturally sensitive clinical practices. This review underscores the therapeutic potential of zuranolone while also noting the necessity for further research to address safety concerns and optimize treatment protocols.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"20 ","pages":"Article 100293"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}