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

{"title":"Changes in leukocytes and CRP in different treatments of major depression.","authors":"Ammar Abo Hwach, Seda Nur Türker, Franziska Huster, Anastasia Gaspert, Alborz Bastami, Joana Wrasse, Stefan Bleich, Helge Frieling, Thomas Nickl-Jockschat, Hannah Benedictine Maier, Alexandra Neyazi","doi":"10.1007/s00702-026-03187-z","DOIUrl":"10.1007/s00702-026-03187-z","url":null,"abstract":"<p><p>Neuroinflammatory mechanisms have long been implicated in the pathophysiology of depression, particularly in treatment-resistant depression (TRD). Peripheral immune markers such as monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-platelet ratio (NPR) may reflect chronic or acute immune activation and could serve as potential biomarkers for treatment response. We analyzed differential blood cell counts and inflammatory ratios (MLR, NLR, NPR), as well as interleukin-6 (IL-6) and C-reactive protein (CRP) levels, in 196 patients with severe depression. Patients were grouped into unmedicated (UDC), TRD with medication only (TRD-M), and TRD with electroconvulsive therapy (TRD-ECT), and were assessed at baseline and after four weeks. TRD patients showed significantly higher monocyte and MLR levels than non-TRD patients. Within TRD, ECT responders exhibited lower monocyte and MLR values compared to non-responders. NLR levels were significantly higher in the ECT group. A positive correlation was found between NPR changes and symptom improvement based on Beck Depression Inventory-II scores (BDI-II). Our findings suggest that TRD is associated with a chronic inflammatory profile, and that ECT may induce a shift toward acute immune activation, potentially contributing to treatment response. MLR, NLR, and NPR may serve as potential biomarkers and should be evaluated in prospective studies with larger samples and detailed immune phenotyping.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2521-2534"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371729","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":"Stress and Parkinson's disease: from dysfunctional detection to impaired handling: a narrative review.","authors":"Nico J Diederich, Claire Pauly","doi":"10.1007/s00702-026-03267-0","DOIUrl":"10.1007/s00702-026-03267-0","url":null,"abstract":"<p><p>Stress can precipitate Parkinson's disease (PD), and conversely, PD imposes substantial stress on affected individuals. Controlled studies support this bidirectional relationship. Recent observations during the Covid‑19 pandemic suggested that PD patients may sometimes display an unexpected resilience to stressful events (SE), in particular in terms of missing motor deterioration. However, this \"favorable\" interpretation can be misleading as PD is characterized by dysfunctional stress detection and stress processing. Furthermore, reduced stress‑related cardiac morbidity has not been demonstrated uncontestably. Indeed, detailed analyses indicate that involvement of non‑dopaminergic systems modifies-rather than mitigates-stress responses. Lewy body pathology already compromises activation of the hypothalamic-pituitary-adrenal (HPA) axis, while autonomic cardiac responses are blunted. Dysfunction of the superior colliculi impairs instant detection of stress events (SE); degeneration of the pedunculopontine nucleus disrupts appropriate motivational appraisal of the SE. Impaired contrast discrimination and olfaction hinder immediate perceptual SE assessment. Locus coeruleus involvement reduces alertness, further limiting SE evaluation. Finally, at the nexus of stress handling, dysfunctional amygdalar networks contribute to diminished autonomic reactivity and altered emotional processing. This review synthesizes current knowledge on peripheral and central stress‑related systems affected by PD pathophysiology. It outlines established, emerging, and theoretical therapeutic strategies, including approaches informed by the Stress Reduction Theory and the Attention Restoration Theory. It underscores the need for systematic investigation into stress mechanisms in PD, an area that remains insufficiently explored.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2211-2229"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043336","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":"Multimodal assessment of clinical and neural changes following multidisciplinary management in functional motor disorders.","authors":"Marialuisa Gandolfi, Angela Sandri, Elisabetta Sarasso, Andrea Gardoni, Michela Russo, Silvia Basaia, Ilaria Antonella Di Vico, Roberto Erro, Serena Camozzi, Giulia Pedrotti, Melania Fasoli, Francesca Salaorni, Christian Geroin, Giancarlo Mansueto, Francesca Benedetta Pizzini, Marco Barillari, Matteo Francesco Lauriola, Mariachiara Tozzi, Francesca Rusciano, Anna Fratucello, Sofia Cuoco, Immacolata Carotenuto, Carlo Ricciardi, Francesco Amato, Claudia Vinciguerra, Annibale Botto, Daniele Romano, Marianna Amboni, Mirta Fiorio, Angela Marotta, Giovanna Maddalena Squintani, Sara Mariotto, Stefano Tamburin, Fabio Paio, Giuseppe De Biasi, Giuseppe Piscosquito, Elisa Canu, Paolo Barone, Massimo Filippi, Michele Tinazzi, Maria Teresa Pellecchia, Federica Agosta","doi":"10.1007/s00702-026-03254-5","DOIUrl":"10.1007/s00702-026-03254-5","url":null,"abstract":"<p><p>Functional motor disorders (FMD) are common and disabling conditions, but objective biomarker changes following multidisciplinary management remain limited. Our objective was to investigate changes and responsiveness of multimodal biomarkers in individuals with FMD undergoing multidisciplinary management. 34 patients with clinically definite FMD (mean age 42.76 ± 11.01 years; 85.7% female; mean disease duration 0.64 ± 1.52 years) underwent a standardized multimodal assessment at baseline and 3-month follow-up after a multidisciplinary program. The intervention included a 5-day intensive rehabilitation program (2 h/day), followed by a 12-week phase of telemedicine (one session every 2 weeks) and home-based self-management (two sessions/week). Multimodal biomarkers across motor, exteroceptive, interoceptive, and brain function domains were assessed using clinical, neurophysiological, and task-based functional MRI measures. Motor symptoms improved with concurrent gains in depressive symptoms, physical quality of life, and fatigue (all, p < 0.047). Specific improvements were observed in motor performance, including reduced stride time variability during cognitive dual-tasking (p = 0.018) and enhanced postural stability mainly in the eyes-closed condition (all, p < 0.028), while neurophysiological and nociceptive measures remained unchanged. Patients showed altered baseline brain activity compared with controls; post-intervention changes were observed in motor, cerebellar, and fronto-insular regions (p < 0.001, uncorrected), without correlations with clinical outcomes. Multidisciplinary management in FMD was associated with improved clinical outcomes and specific motor and neural changes, suggesting domain-specific responsiveness and a potential role for multimodal biomarkers, requiring confirmation in larger controlled studies. Trial Registration number NCT06328790. Registered on 26 March 2024.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2733-2743"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681997","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":"Myopathies in clinical care: a focus on treatable causes.","authors":"Genevieve C Uy, Raymond Rosales, Satish Khadilkar","doi":"10.1007/s00702-026-03117-z","DOIUrl":"10.1007/s00702-026-03117-z","url":null,"abstract":"<p><p>Myopathies are a group of disorders that affect the skeletal muscles, manifesting as weakness, fatigue, or pain. Generally, they are classified as acquired or inherited. It is important to note that while most acquired myopathies are treatable, in the advent of targeted molecular and gene-based therapy, some inherited forms now have effective therapeutic options. These myopathies can be classified based on their underlying causes, including infections, autoimmune disorders leading to muscle inflammation, metabolic abnormalities within muscle cells, skeletal muscle channel dysfunctions, critical illness myopathy, and inherited conditions such as muscular dystrophies. In this review, we first present a clinical approach to neuromuscular diseases and subsequently place specific emphasis on myopathies, particularly those with established or emerging treatment options.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2023-2054"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318117","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":"HDL cholesterol indicates neurodegenerative vulnerability in dementia with lewy bodies.","authors":"Tadashi Umehara, Masahiro Mimori, Masakazu Ozawa, Tomotaka Shiraishi, Tomomichi Kitagawa, Hiromasa Matsuno, Shusaku Omoto, Renpei Sengoku, Hidetomo Murakami, Yasuyuki Iguchi","doi":"10.1007/s00702-026-03115-1","DOIUrl":"10.1007/s00702-026-03115-1","url":null,"abstract":"<p><p>Altered lipid metabolism has been implicated in neurodegenerative disorders; however, its relevance to dementia with Lewy bodies (DLB) remains incompletely characterized. This study examined associations between plasma lipid profiles, lipid-related inflammatory indices, and clinical and neurodegenerative features in drug-naive patients with DLB, with comparisons to age-matched healthy controls. Plasma levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol did not differ significantly between patients with DLB and controls, whereas triglyceride (TG) levels were significantly lower in DLB (p = 0.002). Within the DLB cohort, higher HDL-C levels were associated with less severe neurodegenerative changes, including milder nigrostriatal degeneration (β = 0.448, p = 0.005), lower motor symptom severity (β = -0.324, p = 0.047), and a reduced prevalence of visual hallucinations (OR = 0.924, p = 0.006). In contrast, higher TG levels and an increased TG-to-HDL-C ratio were associated with more pronounced neurodegenerative involvement (TG: β = -0.358, p = 0.021; TG-to-HDL-C ratio: β = -0.426, p = 0.006). Greater neurodegenerative severity was also associated with lipid-related inflammatory markers, including the neutrophil-to-HDL-C ratio (β = -0.491, p = 0.001) and the platelet-to-HDL-C ratio (β = -0.301, p = 0.040), suggesting that inflammation may act as a contributory or mediating process. Collectively, these findings indicate that plasma lipid profiles-particularly HDL-C-are associated with neurodegeneration and clinical manifestations in DLB, extending beyond isolated dopaminergic involvement. An HDL-C-related neurodegenerative framework, with inflammation as a modifying process, may better reflect the underlying pathophysiology of DLB and warrants further longitudinal investigation.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2329-2338"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146134023","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":"Serotonin deficiency caused by inactivation of Tph2 in mice leads to widespread sex-dependent changes in cerebral oxidative metabolic activity.","authors":"Pilleriin Kupper, Margus Kanarik, Marianna Norden, Angelika G Schmitt-Böhrer, Ruth Shimmo, Klaus-Peter Lesch, Jaanus Harro","doi":"10.1007/s00702-026-03265-2","DOIUrl":"10.1007/s00702-026-03265-2","url":null,"abstract":"<p><p>Tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of serotonin synthesis in the CNS, has been associated with numerous behavioural traits and psychiatric disorders. Tph2 modified mice present altered sensitivity to stress, and excessively aggressive behaviour that develops even in female animals. We have measured histochemically the activity of cytochrome c oxidase (COX) in 106 brain regions in wildtype, Tph2 heterozygous and total knockout male and female mice (n=78). In addition to direct comparisons by sex and genotype, COX activity co-variation in putative aggression networks was examined. Overall, female mice have higher COX activity than males. In regions affected by Tph2 inactivation a consistent pattern emerged, where Tph2^± mice had the lowest, Tph2^-/- mice had the highest COX activities, and Tph2^+/+ in-between. Tph2 inactivation induced broad changes and an extensive reorganisation of neural activity as revealed by regional activity co-variation matrices of COX. These patterns of inter-regional correlations differed between sexes. Co-variation of COX activity also differed between males and females in the proposed networks for aggressiveness. In male mice, Tph2 inactivation disrupted co-variation of COX activity of the dorsal raphe and the periaqueductal grey matter with limbic regions. The septum appears as a hub of altered connectivity in females but not in males. Serotonin deficiency is associated with altered regional neural activity patterns as revealed by COX histochemistry. These alterations are profoundly different in male and female mice, and suggest that serotonin plays a partly sex-dependent role in the regulation of behaviour.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2769-2785"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805277","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 refined protocol for the large-scale production of high-quality cerebral organoids.","authors":"Tatyana Prokhorova, Sonja Simone Hohmann, Alessia Fabozzi, Silvia Saltarelli, Vyacheslav Akimov, Cristine Marie Yde Ohki, Rhiannon V McNeill, Christian Tvedesøe, Blagoy Blagoev, Sarah Kittel-Schneider, Peter Schneider-Kamp, Lukasz Smigielski, Jing Qin, Birgit Debrabant, Edna Grünblatt, Tanja Maria Michel","doi":"10.1007/s00702-026-03216-x","DOIUrl":"10.1007/s00702-026-03216-x","url":null,"abstract":"<p><p>Human pluripotent stem cell-derived cerebral organoids have emerged as a valuable tool for investigating early brain development and modeling neurodevelopmental disorders. However, considerable variation in both organoid size and cellular composition has been widely reported. Moreover, the large-scale production of organoids using conventional methods is a significant challenge, particularly considering that some stem cell lines exhibit variable efficiency in neuroepithelial formation. This heterogeneity of cerebral organoids can complicate experimental reproducibility and comparability in studies of brain development and disease mechanisms. Therefore, we developed a protocol using CERO 3D bioreactors, which enables scalable organoid production and improves size homogeneity compared to conventional approaches. In addition, we conducted a pilot study, utilizing MS-based proteomic analysis of single organoids from two different lines, aiming to explore whether size variability is associated with differences in protein expression within cerebral organoids. The organoids produced in the CERO 3D bioreactors reproducibly form neuroepithelial structures and express key neurodevelopmental markers. The presented protocol provides an efficient way of producing cerebral organoids, supporting reproducibility and high-throughput applications in neurodevelopmental research.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2839-2851"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379564","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":"Stress and resilience: cortisol hypo-response to acute stress in non-resilient individuals.","authors":"Nadine D Riske, Charlotte Schenk, Kira F Ahrens, Bianca Kollmann, Danuta Weichert, Nadine Steinbach, Jana F Burlage, Florian Freudenberg, Klaus Lieb, Raffael Kalisch, Oliver Tüscher, Maren Schmidt-Kassow, Andreas Reif, Michael M Plichta","doi":"10.1007/s00702-026-03218-9","DOIUrl":"10.1007/s00702-026-03218-9","url":null,"abstract":"<p><p>Resilience-the outcome of effective adaptation to adversity-is a dynamic construct referring to the preservation or quick recovery of mental health in the face of significant stressors. Despite the crucial role of the acute stress response in coping with adversity, no consensus exists regarding its relationship with resilience. Inconsistent findings may be due to variability in the assessment of resilience. The present study investigates the relationship between resilience and acute stress responses by comparing resilient and non-resilient individuals in their responses to experimentally induced acute stress. A novel approach was used, combining the Socially Evaluated Cold Pressor Test (SECPT) as a reliable and replicable stress induction method with a uniquely characterized sample whose resilience had been assessed in a prior longitudinal study. Based on these longitudinal assessments of stressor reactivity, participants (N = 48) were classified as resilient (14 female / 10 male; age in years: M = 34.5, SD = 9.32) or non-resilient (17 female / 7 male; age in years: M = 31.6, SD = 5.52). Salivary cortisol and subjective measures (subjective stress and State Anger) were assessed before and 20 min after stress induction. Resilience was associated with cortisol reactivity, with non-resilient participants showing significantly lower cortisol responses to the SECPT compared to the resilient participants (F(1,45) = 4.252, p= 0.045). Subjective measures did not differ between groups in terms of reactivity. However, non-resilient participants reported higher overall levels of subjective stress (F(1,43) = 4.780, p= 0.034). It remains to be clarified whether resilience determines cortisol reactivity or whether cortisol reactivity represents a mechanism underlying resilience.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2231-2245"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379543","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":"Levodopa-induced dyskinesia is associated with worse gait and balance in Parkinson's disease.","authors":"Gabriele Imbalzano, Federico D'Agata, Claudia Ledda, Carlo Alberto Artusi, Marco Laudadio, Alberto Romagnolo, Mario Giorgio Rizzone, Leonardo Lopiano, Maurizio Zibetti, Marco Bozzali","doi":"10.1007/s00702-026-03217-w","DOIUrl":"10.1007/s00702-026-03217-w","url":null,"abstract":"<p><p>Levodopa-induced dyskinesia (LID) is a major source of disability in advanced Parkinson's disease (PD), whose impact on gait and balance across medication states still remains unclear. We aimed to compare gait and balance performance between comparable dyskinetic (Dysk-matched) and non-dyskinetic (No-Dysk) PD patients in OFF and ON state, and to explore neural correlates using structural and resting-state functional MRI (rs-fMRI). PD patients were consecutively enrolled among candidates for device-aided therapies. Gait and balance were assessed using validated wearable inertial sensors during a 2-minute walk test, a 3-meters Timed-Up-and-Go (TUG), and a sway test, providing spatiotemporal gait parameters, variability, asymmetry, and postural sway metrics. Groups were compared using propensity score matching (PSM) for age, sex, disease duration, motor severity and axial disability. A subgroup underwent exploratory investigation with structural and rs-fMRI collected in ON state. After PSM (22 pairs), Dysk-matched group showed slower gait speed (p = 0.007), shorter stride length (p = 0.006), longer double support (p = 0.047), and prolonged TUG (p = 0.049) in the OFF state. Dysk-matched patients showed increased sway from OFF to ON (p = 0.030). Neuroimaging (10 Dysk-matched, 9 No-Dysk) revealed increased functional connectivity in sensorimotor regions and reduced SMA connectivity within a cerebellar network in Dysk-matched patients, without structural difference. Overall, the association of LID with impaired gait and postural control even in the OFF state is consistent with the hypothesis of broader motor network dysfunction beyond overt involuntary movements.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2589-2598"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355385","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":"Multidimensional pain patterns in Parkinson's disease: a longitudinal mobile health study.","authors":"Eduardo Souza-Silva, Ana Carolina Ruver-Martins, Amanda Karoline Venceslau Cassenotte, Fabiana Noronha Dornelles, Marina Bueno Recchia, Carolina Franchi de Souza Sá, Filipe Carvalho Matheus, Samantha Cristiane Lopes, Rui Daniel Prediger","doi":"10.1007/s00702-026-03250-9","DOIUrl":"10.1007/s00702-026-03250-9","url":null,"abstract":"<p><p>Pain is a non-motor symptom of Parkinson's disease (PD). In clinical practice, it is often reduced to single metrics, such as intensity, omitting important aspects of its complexity. Mobile health tools enable repeated recording and multidimensional analysis of pain. To examine how pain intensity, duration, and spatial distribution differentiate patient profiles using longitudinal mobile health data. We analyzed 20,971 daily records from 68 PD patients over 14 months. Patients reported pain intensity, episode duration, and pain location. Data were aggregated at the individual level to avoid pseudo-replication. Profiles were identified using unsupervised clustering (HDBSCAN with KMeans fallback). Associations between pain dimensions were assessed using Spearman correlation. Two profiles were identified: a high-burden group (n = 17) and a low-burden group (n = 50). One additional cluster (n = 1) was excluded due to instability. Differences between groups were greater for cumulative pain duration (6.7-fold) and spatial extent (9-11-fold) than for mean intensity (2.4-fold). Mean pain intensity was moderately correlated with cumulative duration (ρ = 0.66) and spatial extent (ρ = 0.60 anterior; ρ = 0.44 posterior), whereas mean episode duration showed weak and non-significant associations with other pain metrics. Recording frequency was not associated with cluster membership (r = 0.16, p = 0.20), and both groups showed sustained engagement. Pain intensity alone may not adequately reflect overall burden in PD. Considering temporal persistence and spatial distribution provides a more complete view of patient experience and supports a multidimensional approach to assessment.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2701-2713"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623733","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}