Journal of neural transmission (Vienna, Austria : 1996)最新文献

{"title":"Visual memory in Parkinson's Disease: a non-graphomotor approach to assessment.","authors":"Mahima Bhardwaj, Shweta Prasad, Keshav J Kumar, Tarunya Nagaraj, Shubha G S Bhat, Pooja Mailankody, Rohan R Mahale, Vikram V Holla, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal","doi":"10.1007/s00702-026-03181-5","DOIUrl":"10.1007/s00702-026-03181-5","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive motor disorder with multiple motor and non-motor symptoms. Cognitive decline, particularly memory deficits are well documented phenomenon due to its importance as potential biomarkers. While substantial research has explained mechanisms and findings related to deficits in verbal learning and memory, deficits across visual learning and memory are comparatively under-documented. They are often inconsistent due to the reliance on traditional paper-pencil based tests which are susceptible to confounding by motor symptoms and graphomotor deterioration seen in PD. This study aims to explore the usefulness of the Wechsler Memory Scale-IV (WMS-IV) as a non-graphomotor method to testing visual memory profiles in PD. Performance on subtests of the WMS-IV was compared between 113 patients with PD and 90 education-matched healthy controls (HC) with stratification based on literacy into literate, functional illiterate and illiterate. Significant differences were observed on sub-tests of Symbol Span and Designs I(Content) scores between the PD groups and their corresponding HC irrespective of education level. Only the literate PD group showed significant differences from their HC on spatial addition subtests. On the Designs I and II spatial scores, functional illiterates, did not differ from their corresponding HC while the literate and illiterate Groups continued to differ. These findings highlight the need to adapt traditional visual learning and memory tests to PD in order to elicit truly representative deficits, and the need to develop alternative versions that are not driven by education with localised education-based norms. These will permit accurate and equitable profiling across literacy backgrounds.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2513-2520"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944679","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":"Effects of acute physical activity on interference control in children with and without ADHD: a crossover ERP study from the Break4Brain project.","authors":"Adrià Muntaner-Mas, Antònia Siquier, Olalla García Taibo, Diego Arenas, Jaume Cantallops Ramon, Alejandro Galvez-Pol, Víctor Sánchez-Azanza, Daniel Adrover-Roig, Juan L Terrasa, Carolina Sitges","doi":"10.1007/s00702-026-03234-9","DOIUrl":"10.1007/s00702-026-03234-9","url":null,"abstract":"<p><p>Physical activity (PA) has been associated with improvements in inhibitory control in children, including those with attention-deficit/hyperactivity disorder (ADHD). However, the relative contribution of different PA types, particularly those differing in cognitive engagement, remains unclear. This study examined behavioural and electrophysiological indicators of interference control in children with and without ADHD following three conditions: PA with alternating cognitive engagement, PA without cognitive engagement, and a cognitively engaging control condition. Forty-three children, 20 with ADHD and 23 without ADHD, completed all sessions in a randomized crossover design. Interference control was assessed using a Flanker task while electroencephalography was recorded. Reaction time, accuracy, and interference effects were analysed at baseline and after each condition, with post-condition sessions separated by one week. N2 and P3 amplitudes were examined as electrophysiological indices of conflict monitoring and attentional allocation, respectively. The interference effect was reduced after the cognitively engaging control condition and PA without cognitive engagement relative to baseline, although no condition produced overall changes in reaction time or accuracy. EEG analyses showed larger N2 amplitudes after PA without cognitive engagement and reduced P3 amplitudes after the cognitively engaging control condition and PA without cognitive engagement compared with baseline. Overall, PA without cognitive engagement and the cognitively engaging control condition elicited acute modulations of behavioural and neural markers of interference control, irrespective of ADHD status. These findings suggest that brief PA bouts may modulate ERP indices related to executive-function processes in children, although the functional significance of reduced P3 amplitude remains uncertain when behavioural effects are limited.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2671-2686"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623766","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":"Investigating smiling asymmetries in Parkinson's disease through the whistle-smile reflex.","authors":"Adriana Martini, Giulia Paparella, Simone Aloisio, Luca Angelini, Anna Sofia Grandolfo, Martina De Riggi, Daniele Birreci, Davide Costa, Luca Marsili, Matteo Bologna","doi":"10.1007/s00702-026-03193-1","DOIUrl":"10.1007/s00702-026-03193-1","url":null,"abstract":"<p><strong>Background: </strong>Hypomimia is a hallmark of Parkinson's disease (PD), but whether emotional expressions show lateralized abnormalities remains unclear. While asymmetry has been described for posed smiles, no study has examined true spontaneous smile asymmetry in PD. The whistle-smile reflex (WSR), an involuntary smile elicited after voluntary whistling, offers an opportunity to investigate a form of smiling that closely resembles typical spontaneous expressions of joy. In the present study, we aimed to assess the frequency, intensity, and asymmetry of smiling elicited by the WSR in PD compared with healthy controls (HCs) and to explore links between facial and motor asymmetry. Fifty PD patients and 22 age-matched HCs underwent standardized video recording of the WSR. Only participants judged as smiling by ≥ 3/4 raters were included in the chimeric-face analysis. Left-left (LL) and right-right (RR) chimeric images were generated, and seven blinded raters evaluated smile presence and hemiface expressivity. Facial Laterality Index (FLI) and Body Laterality Index (BLI) quantified asymmetries. WSR was less frequent in PD than HCs (video: 44% vs. 72%; mouth-only chimeras: 50% vs. 81%, p < 0.01). PD smiles were more often symmetrical (59% vs. 25%, p = 0.03), with no consistent left-right dominance. Facial and motor asymmetry were unrelated (p > 0.05). Symmetric smilers had higher UPDRS-III scores (p = 0.04). In PD, WSR is reduced and bilaterally flattened, with no lateralized asymmetry, possibly reflecting limbic-subcortical dysfunction. Smile symmetry increases with motor severity, supporting its potential as a simple marker of hypomimia. The WSR and chimeric-smile analysis provide practical tools to assess emotional expressivity in PD.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2535-2546"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"¹²³I-FP-CIT uptake and behavioral disinhibition in the frontotemporal dementia spectrum: an exploratory DAT-SPECT study.","authors":"Shigeki Katakami, Yuto Satake, Daiki Taomoto, Yuhei Okura, Matasaburo Kobayashi, Kayo Takeda, Fuyuki Koizumi, Takashi Suehiro, Kohji Mori, Manabu Ikeda, Kenji Yoshiyama","doi":"10.1007/s00702-026-03262-5","DOIUrl":"10.1007/s00702-026-03262-5","url":null,"abstract":"<p><p>Behavioral disinhibition is a core feature of behavioral variant frontotemporal dementia (bvFTD) and occurs across related FTD-spectrum presentations. Serotonergic dysfunction may contribute to behavioral dysregulation; therefore, we primarily examined dorsal raphe (DR)-centered midbrain ¹²³I-FP-CIT uptake as an indirect extrastriatal signal that may partly reflect serotonin transporter-related binding. Because striatal dopaminergic circuits support reward learning, behavioral inhibition, and context-dependent behavioral updating, striatal uptake was examined exploratorily. This retrospective exploratory study included 21 patients within the FTD spectrum who underwent Neuropsychiatric Inventory (NPI) assessment, magnetic resonance imaging, and ¹²³I-FP-CIT single-photon emission computed tomography within a 3-month window. The primary outcome was the NPI disinhibition score. DR-centered midbrain and striatal specific uptake ratios (SURs) were calculated using the cerebellum as the reference region. Age- and sex-adjusted quasi-Poisson models with a log link were fitted. DR-centered midbrain SUR was not significantly associated with disinhibition in the primary model (β = -1.027, p = 0.353). In the exploratory model, higher striatal SUR was nominally associated with lower disinhibition scores (β = -0.438, p = 0.022). The negative direction of the striatal association was generally preserved across sensitivity analyses, although nominal significance was not retained in all models. DR-centered midbrain SUR was not significantly associated with behavioral disinhibition in this small FTD-spectrum cohort. Lower striatal SUR showed a directionally consistent but sensitivity-dependent nominal association with greater disinhibition. This hypothesis-generating finding may reflect broader frontostriatal disease burden, striatal neurodegeneration, parkinsonian-spectrum overlap, or partial-volume effects and does not establish a disinhibition-specific dopaminergic mechanism.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2279-2290"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world gait changes preceding Parkinson's disease diagnosis in a population-scale UK biobank cohort.","authors":"Paulo H S Pelicioni, Sophie Waller, Lloyd Chan, Arun V Krishnan, Stephen R Lord, Matthew A Brodie","doi":"10.1007/s00702-026-03256-3","DOIUrl":"10.1007/s00702-026-03256-3","url":null,"abstract":"<p><p>Parkinson's disease (PD) has a long prodromal phase characterised by non-motor symptoms and subtle motor dysfunction, including changes in gait. While early gait abnormalities have been described in high‑risk populations, less is known about how real‑world gait behaviour changes prior to diagnosis in the general population. To investigate whether digital gait biomarkers derived from wrist‑worn sensors are associated with future Parkinson's disease diagnosis. The study comprised 73,413 UK Biobank participants who wore a wrist-worn device for seven days. Seventeen digital gait biomarkers were derived using the Watch Walk algorithm. Participants were followed for up to 10 years through linked electronic health records, and associations with time to PD diagnosis were assessed using Cox regression models adjusted for age and sex. Of the 73,294 participants without PD at the accelerometry assessment, 314 were diagnosed with PD during follow-up. Compared with those who did not develop PD, those who did had lower daily step counts (6370 vs. 4043-5585 steps/day), with greater differences observed closer to diagnosis, as well as slower walking speeds, altered step regularity, and reduced arm swing at baseline (all p < 0.001). Across groups stratified by time to PD onset, five gait measures (daily step count, maximum walking speed, step regularity, proportion of long walking bouts, and time spent walking with static arm positions) were consistently associated with subsequent PD diagnosis (all p < 0.001). Differences in real‑world gait behaviour were observable years before PD diagnosis in this large population cohort. These findings suggest that digital gait biomarkers may help characterise early motor changes detectable up to 6.8 years before a clinical diagnosis of PD.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2745-2755"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-COVID: a specific neuropsychological profile in performance deficits.","authors":"Britta Müller, Ulrike Balz, Katharina Bartels, Farina Eggers, Micha Löbermann, Luise Nostitz, Juliane Schmidt, Carola Schwarz, Christine Wossidlo, Emil C Reisinger, Peter Kropp","doi":"10.1007/s00702-026-03209-w","DOIUrl":"10.1007/s00702-026-03209-w","url":null,"abstract":"<p><strong>Background: </strong>SARS-CoV-2 is frequently associated with cognitive impairment. When symptoms persist for more than four weeks after acute infection, a Long-COVID condition is diagnosed. When persisting more than 12 weeks, Post-COVID ist diagnosed. Cognitive complaints commonly include impairments in attention, memory, and executive functions. However, precise data on the specific pattern and extent of these deficits remain limited.</p><p><strong>Methods: </strong>Results: Conclusions: The findings indicate that attentional impairments are more prevalent than memory deficits in this Post-COVID cohort. Furthermore, distinct cognitive profiles can be identified using cluster analysis, ranging from globally impaired to cognitively preserved subgroups. These results may be relevant for clinical characterization and rehabilitation planning in Post-COVID conditions.</p><p><strong>Methods: </strong>We examined 88 patients (mean age 50.9 years, 80.7% female) diagnosed with COVID symptoms according to the WHO-criteria. Neuropsychological assessment was performed using a standardized test battery covering attentional performance, working memory, and executive functions. A cluster analysis was conducted to identify subgroups based on cognitive performance profiles.</p><p><strong>Results: </strong>Overall, 55.7% of patients showed below-average attentional performance, whereas memory deficits were less frequent (33.0%). Impairments in executive functions were similarly distributed across the sample. Cluster analysis yielded a three-cluster solution. Cluster 1 (34.1%) was characterized by pronounced impairments across all cognitive domains. Cluster 2 (20.0%) showed generally below-average cognitive performance; however, verbal fluency was preserved at or above average in all participants. In Cluster 3 (17.6%) more than 50% of patients in performed within average to above-average ranges across all cognitive domains.</p><p><strong>Conclusions: </strong>The findings indicate that attentional impairments are more prevalent than memory deficits in this Post-COVID cohort. Furthermore, distinct cognitive profiles can be identified using cluster analysis, ranging from globally impaired to cognitively preserved subgroups. These results may be relevant for clinical characterization and rehabilitation planning in Post-COVID conditions.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2567-2575"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic drug monitoring in children and adolescents treated with quetiapine for different psychiatric disorders: results of the TDM-VIGIL pharmacovigilance study.","authors":"Alina Kaiser, Karin Maria Egberts, Hans-Willi Clement, Marcel Romanos, Andreas Karwautz, Paul L Plener, Christoph U Correll, Uwe Malzahn, Peter Heuschmann, Stefan Unterecker, Maike Scherf-Clavel, Hans Rock, Tobias Banaschewski, Hartmut Imgart, Michael Kaess, Tobias Renner, Su-Yin Reuter-Dang, Gerd Schulte-Körne, Frank Theisen, Susanne Walitza, Christian Fleischhaker","doi":"10.1007/s00702-026-03253-6","DOIUrl":"10.1007/s00702-026-03253-6","url":null,"abstract":"<p><p>Although quetiapine is increasingly used off-label in children and adolescents with various psychiatric disorders, there is little evidence on the relationship between quetiapine dose and serum concentration, and therapeutic reference ranges (TRR) have not yet been established for this age group. The aim of this study was to evaluate whether the TRR described for adults is applicable to minors. In addition, the study aimed to investigate the relationship between the daily dose, serum concentration and clinical outcome. The clinical course of 77 patients (females = 78%) aged between 12 and 17 years treated with quetiapine in the multicentre pharmacovigilance study TDM-VIGIL was systematically followed, and serum concentrations were measured. A positive mean correlation was observed between the weight-adjusted daily dose and serum concentration (r_s = 0.580, p < 0.001). Most patients (84.7%) experienced no ADRs or ADRs not significantly interfering with the patients' functioning. A positive linear relationship between the therapeutic response and serum concentration was found (r_s = 0.238, p = 0.006). Only 38.5% of all quetiapine serum concentrations were within the recommended TRR described for adults. Using two different calculation methods, mean ± SD and IQR, our data hinted at considerably lower TRR for minors of about 14-291 ng/ml and 53-234 ng/ml respectively, compared to the suggested TRR for adults. This study has the potential to contribute to the definition of a TRR for quetiapine in minors. However, further controlled studies with larger sample sizes are needed to verify the preliminary results.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2715-2731"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote smartphone-based spoken language screening predicts clinical markers in Huntington's disease.","authors":"Martin Šubert, Tomáš Kouba, Tereza Tykalová, Olga Klempířová, Alzbeta Mühlbäck, Jiří Klempíř, Jan Rusz","doi":"10.1007/s00702-026-03173-5","DOIUrl":"10.1007/s00702-026-03173-5","url":null,"abstract":"<p><p>Assessment and monitoring of Huntington's disease (HD) symptoms remain limited to infrequent, clinic-based evaluations. We evaluated whether fully automated linguistic analysis of speech tasks recorded via smartphone can remotely capture core clinical markers of HD severity. In this cross-sectional multicenter study across Czech and German sites, 53 participants, including 30 HD (9 pre-symptomatic, 3 prodromal, and 18 manifest) and 23 healthy controls, completed a smartphone-based speech assessment, including spontaneous monologue and fairy tale retelling for 7 consecutive days. Recordings were automatically transcribed and analyzed using natural language processing to derive 3 lexical and 3 syntactic features. Predictive models for clinical outcomes based on the Unified Huntington's Disease Rating Scale and cognitive scales were built using multivariate linear regression with cross-validation. Linguistic features predicted HD severity across multiple domains with high predictive performance, explaining up to 57% of the variance in cognitive performance, 63% in motor impairment, and 59% in functional capacity. A median of 6 days for monologue and 3 for retelling was sufficient to reach 90% of maximal predictive performance. Compared to controls, HD participants showed reduced vocabulary range and increased phrase repetition in both tasks (p < 0.05), with additional monologue-specific deficits in sentence length (p = 0.018) and syntactic complexity (p = 0.004). Fully automated analysis of smartphone-based language assessment can remotely quantify cognitive, motor, and functional impairment in HD, offering a scalable, low-burden digital biomarker for clinical trials and decentralized monitoring.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2479-2490"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automatic neural mechanisms of social synchrony: pupil and Blink responses in adults with ADHD symptoms.","authors":"Or Lipschits, Sapir Sadon, Ronny Geva","doi":"10.1007/s00702-025-03051-6","DOIUrl":"10.1007/s00702-025-03051-6","url":null,"abstract":"<p><p>Human social interactions involve both conscious behaviors, such as speech and gestures, and automatic responses regulated by dopaminergic and noradrenergic neural networks, including pupil dilation and blinking. Dysfunctions in dopamine and noradrenaline activity, common in ADHD, impair automatic social processes such as physiological synchrony and anticipation, leading to broader difficulties in social cognition and interpersonal relationships. Shifting the lens from overt behaviors to automatic processes that lie at the core of social interaction, the present study examined whether adults with ADHD indication (ADHD-Ind) respond differently to a simulated social cue from those without ADHD-Ind. Sixty young adults (16 ADHD-indicated, 44 controls; 20-35 years) watched nine 6-s clips where on-screen eyes blinked twice or four times while eye-tracking recorded blink timing and pupil size. While global measures did not differ between groups, time-locked analyses of blink synchrony to simulated social cues emerged in the control group-particularly around the onset of simulated blinks. In contrast, synchrony effects are attenuated or absent in individuals with ADHD indications. For pupil dynamics, group differences emerged in the sparse simulated blinking condition, where ADHD-Ind showed reduced dilations from - 80 to 560 ms compared to controls and between - 40 and 400 ms compared to the frequent condition. No group differences appeared in the frequent condition. Further, Higher ADHD symptomatology predicted lower blink synchrony and alterations in the pupil time course. The study underscores the added value of automatic, non-verbal synchrony as potential communicative biomarkers for Neuro-Developmental Disorders, and specially in ADHD. Together, the findings suggest that, in alignment with social cue dynamics, timing- and context-specific alterations-rather than global differences-impede social functioning in individuals with ADHD.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2877-2889"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered iron metabolism and iron therapy in restless legs syndrome.","authors":"Zhikui Wei, Chrsitopher J Earley","doi":"10.1007/s00702-026-03274-1","DOIUrl":"10.1007/s00702-026-03274-1","url":null,"abstract":"<p><p>Restless legs syndrome (RLS) is a common neurological disorder that impairs sleep and reduces quality of life. The pathogenesis of RLS is incompletely understood. However, two mechanisms in its pathogenesis have been well accepted: iron deficiency, particularly brain iron deficiency, and subsequent dopamine dysregulation, which contribute to sensorimotor symptoms in RLS. In this review, we aim to provide a balanced synthesis of the literature on peripheral and brain iron dysregulation and iron therapy in RLS. We conclude that brain iron deficiency is central to the pathogenesis of RLS, whereas peripheral iron deficiency, although closely linked to RLS, poorly reflects brain iron status. Brain iron deficiency in RLS likely arises from altered iron metabolism at multiple levels, including impaired iron transport at the blood-brain interface and in subcortical neuronal structures such as the dopaminergic and thalamic systems, and potentially altered iron export, with or without systemic iron deficiency. These processes are further modulated by circadian-related changes, genetic susceptibility, and sex differences, adding complexity to iron dysregulation in RLS. Iron therapy, both oral and IV formulations, has become a standard of care in the treatment of RLS. Further research is needed to deepen our understanding of brain iron deficiency, improve the prediction of treatment response, and optimize the selection of iron therapies for RLS.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2187-2200"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}