Journal of Neural Transmission最新文献

{"title":"An orthogonal approach for analysis of underivatized steroid hormones using ultrahigh performance supercritical fluid chromatography-mass spectrometry (UHPSFC-MS).","authors":"Perry Devo, Victoria Cretu, Harsha Radhakrishnan, Darren Hamilton-Pink, Stergios Boussios, Saak V Ovsepian","doi":"10.1007/s00702-024-02862-3","DOIUrl":"https://doi.org/10.1007/s00702-024-02862-3","url":null,"abstract":"<p><p>The crucial role of steroid hormones in health and diseases merits their high-throughput, accurate and affordable measurements in biological specimens. Despite advances in analytical methods, sensing and quantifying steroid hormones remains challenging. Immunoassays offer excellent sensitivity but are inherently labour-intensive, costly, and prone to false positives. Mass spectrometry (MS) has been increasingly utilised, with the main hurdle being the isobaric tendencies of similar analytes, which complicates their separation and accurate quantification. This study compares ultrahigh-performance supercritical fluid chromatography separation (UHPSFC) and ultra-high-performance liquid chromatography (UHPLC) for MS detection. It optimises the column chemistry, temperature, and pressure to provide an operational protocol for the resolution and quantification of analytes. It presents the systematic characterisation of UHPSFC-MS performance by investigating spiked blood samples using Solid-Phase Extraction (SPE) and describes the matrix effects associated with MS measurements. Although both separation methods showed adequate resolution, specificity, and retention time, UHPSFC-MS was superior for five out of seven columns tested. With added high-throughput capacities, UHPSFC-MS, thus, offers an optimal solution for the analysis of steroid hormones for research, medical chemistry, and clinical diagnostics.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of safinamide in Parkinson's disease patients with motor fluctuations without levodopa dosage escalation over 18 weeks: KEEP study.","authors":"Eungseok Oh, Sang-Myeong Cheon, Jin Whan Cho, Young Hee Sung, Joong-Seok Kim, Hae-Won Shin, Jong-Min Kim, Mee Young Park, Do-Young Kwon, Hyeo Ma, Jeong-Ho Park, Seong-Beom Koh, Seong-Min Choi, Jinse Park, Phil Hyu Lee, Tae-Beom Ahn, Sang Jin Kim, Chul Hyoung Lyoo, Ho-Won Lee, Jieun Kim, Yoona Lee, Jong Sam Baik","doi":"10.1007/s00702-024-02851-6","DOIUrl":"https://doi.org/10.1007/s00702-024-02851-6","url":null,"abstract":"<p><p>This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson's disease (PD) with motor fluctuations with ≥ 1.5 h of \"off\" time daily, who took levodopa ≥ 3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson's Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale, MDS-UPDRS part 3 and part 4; King's Parkinson's Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily \"off\" time (- 1.3 ± 2.4 h, p < 0.001) and quality of life (QoL) based on PDQ-39 summary index (- 2.7 ± 10.3, p < 0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily \"on\" time without dyskinesia (all p < 0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD.Trial registration number and date: NCT05312632, First Posted: April 5, 2022.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional near-infrared spectroscopy and vagus somatosensory evoked potentials add to the power of established parameters such as poor cognitive performance, dsyosmia and APOe genotype to predict cognitive decline over 8 years in the elderly.","authors":"Martin J Herrmann, Alexandra Wuttke, Linda Breuninger, Judith Eff, Sophia Ettlinger, Matthias Fischer, Andrea Götzelmann, Annika Gram, Laura D Pomper, Evelyn Schneider, Lisa Schwitalla, Niklas Siminski, Fabian Spielmann, Erik Weinmann, Viona Weyel, Julia B M Zeller, Martin Lauer, Jürgen Deckert, Thomas Polak","doi":"10.1007/s00702-024-02859-y","DOIUrl":"https://doi.org/10.1007/s00702-024-02859-y","url":null,"abstract":"<p><p>Alzheimer's dementia is the main cause of cognitive impairment in people over the age of 65, with Alzheimer's disease starting presumably 10-15 years before the onset of clinical symptoms. It is therefore important to recognize dementia at an early stage and identify possible predictors. The existing methods, like different parameters of ß-Amyloid and Tau quantification in cerebrospinal fluid (CSF) or the living brain by measure of PET, are invasive and expensive. Therefore, the present study investigates the predictive value of a battery of clinical, neuropsychological, and blood parameters as well as two neurophysiological methods (functional near-infrared spectroscopy [fNIRS] and vagus somatosensory evoked potentials [VSEP]) which are easy to perform, less invasive and cost-efficient, for developing cognitive impairments in the elderly.In this longitudinal, prospective study, we enrolled 604 healthy participants between 70 and 77 years of age. The participants were invited back after a mean time interval of 3 years and 11 months, and after 7 years and 8 months, and their cognitive impairments were determined.Here we show that the development of cognitive impairments after approximately 8 years can be predicted not only by previously known risk factors such as ApoE4 risk alleles, dysosmia, or poor cognitive performance at baseline but that latency prolongation in the VSEP and altered functional activation patterns measured by NIRS at baseline also provide additional predictive value.We therefore suggest that both neurophysiological parameters, VSEP and NIRS, should be included in future studies, investigating the prediction of dementia. Dementia ClinicalTrials.gov Identifier: NCT02224326.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resilience to psychosocial stress and epigenetic aging in schizophrenia: findings from a pilot study.","authors":"George Nader, Muneefah Qureshi, Matisse Ducharme, Corinne Fischer, Philip Gerretsen, Ariel Graff, Daniel Blumberger, Reza Zomorrodi, Carol Borlido, Gary Remington, Vincenzo De Luca","doi":"10.1007/s00702-024-02854-3","DOIUrl":"https://doi.org/10.1007/s00702-024-02854-3","url":null,"abstract":"<p><p>Exposure to stress is known to affect biological aging as well as individuals' susceptibility to a wide variety of mental illnesses, such as schizophrenia. There is an established relationship between the onset of schizophrenia spectrum disorders (SSD) and biological aging. On the other hand, epigenetic modifications, such as DNA methylation (DNAm), are used as biomarkers for biological aging and were previously proven to be altered in schizophrenia. However, previous research did not consider the effect of psychosocial resilience to stress and its effect on aging in schizophrenia, which is what our study aims to address. For our pilot study, 65 schizophrenia patients were recruited and stress exposure and perception levels were assessed using the Social Readjustment Rating Scale (SRRS) and Perceived Stress Scale (PSS), respectively. Moreover, DNA was extracted from venous blood samples and 850,000 CpG loci were assessed for DNA methylation analysis. Average age of participants was 43.15 ± 13.32 years (55.4% male, 44.6% female). Linear regression plots showed significant correlation between SRRS and PSS scores as well as between biological and chronological ages (p < 0.05). The residuals from the two regression models were defined as the psychosocial resilience and DNAm age acceleration, respectively. Interestingly, DNAm age acceleration was inversely correlated with resilience to stress (p < 0.05). In conclusion, it appears that epigenetic age acceleration is associated with reduced resilience to stress in schizophrenia patients. Future studies should focus on establishing resilience effect on disease prognosis.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usability of the digit-tracking technique in a geriatric population of inpatients with and without neurocognitive disorders: The DIGICOG-start study.","authors":"Grégory Ben-Sadoun, Lena Carcreff, Guillaume Sacco, Frédéric Noublanche, Cédric Annweiler","doi":"10.1007/s00702-024-02858-z","DOIUrl":"https://doi.org/10.1007/s00702-024-02858-z","url":null,"abstract":"<p><p>Tools for the early diagnosis of neurocognitive disorders (NCD) both accessible, fast, fun and efficient are currently needed. A digit-tracking technique (Digitrack) has been developed based on the exploration of blurred images on a tablet with the finger, related to the exploration of images during eye-tracking. The present study aimed at assessing the objective usability and the subjective User eXperience (UX) of the Digitrack by older adults according to the presence and the severity of NCD. A total of 135 patients were included in a geriatric acute care unit. Objective usability was assessed through the number of patients able to complete the Digitrack's training (3 images) and evaluation (20 images) phases. UX was measured through standard questionnaires (AttrakDiff and meCUE), and through the description of engagement behaviors following an internally developed scale which included 5 levels (interactive, constructive, active, passive and disengaged behaviors). The success rate of the device was 94.1%. The Digitrack had a very good overall attractiveness, standard hedonic and pragmatic qualities, and the emotions perceived were predominantly positive. These findings were not homogeneously observed in the whole studied population. Patients highly impaired due to NCD tended to rate the device with more neutral scores and to perceive more negative emotions. The participants mainly demonstrated active behaviors, but patients with severe major NCD were mostly passive. The study showed promising results regarding the usability and acceptability of a digit-tracking technique within older adults. Further studies should evaluate the potential of this novel methods to make a cognitive diagnosis.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of tDCS in the treatment of ADHD.","authors":"Ruihan Huang, Yongsheng Liu","doi":"10.1007/s00702-024-02853-4","DOIUrl":"https://doi.org/10.1007/s00702-024-02853-4","url":null,"abstract":"<p><p>TDCS is one of the most widely used non-invasive neuromodulation techniques, which changes the excitability of local cortical tissue by applying weak continuous direct current to the scalp, effectively improves the attention and concentration of ADHD children, and improves the impulse disorder of patients, but related research is still in its infancy. Based on a review of a large number of existing literatures and an analysis of the pathogenesis and principle of ADHD, this paper summarized the research on tDCS in the treatment of ADHD in recent years from the aspects of treatment mechanism, safety and stimulation parameters, and simply compared the application of tDCS with other non-traumatic neuromodulation techniques in the treatment of ADHD. The future development direction of this technology is further discussed.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facets of movement disorders- a tribute to Heinz Reichmann.","authors":"Peter Riederer, Etienne C Hirsch","doi":"10.1007/s00702-024-02857-0","DOIUrl":"https://doi.org/10.1007/s00702-024-02857-0","url":null,"abstract":"","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic drug monitoring in children and adolescents with schizophrenia-spectrum, affective, behavioural, tic and other psychiatric disorders treated with aripiprazole: results of the TDM-VIGIL pharmacovigilance study.","authors":"Jessica Riegger, Karin Maria Egberts, Hans-Willi Clement, Katja Schneider-Momm, Regina Taurines, Stefanie Fekete, Christoph Wewetzer, Andreas Karwautz, Christoph U Correll, Paul L Plener, Uwe Malzahn, Peter Heuschmann, Stefan Unterecker, Maike Scherf-Clavel, Hans Rock, Gisela Antony, Wolfgang Briegel, Tobias Banaschewski, Tobias Hellenschmidt, Michael Kaess, Michael Kölch, Tobias Renner, Christian Rexroth, Gerd Schulte-Körne, Susanne Walitza, Manfred Gerlach, Marcel Romanos, Christian Fleischhaker","doi":"10.1007/s00702-024-02819-6","DOIUrl":"https://doi.org/10.1007/s00702-024-02819-6","url":null,"abstract":"<p><p>Aripiprazole is approved for various severe mental disorders in adults and adolescents. However, off-label prescribing is common, especially in children and adolescents (youth) in whom aripiprazole therapeutic serum level reference ranges are lacking for any disorders. The aim of the study was to evaluate the relationship between aripiprazole dose and serum concentrations and provide further knowledge on the use of aripiprazole in order to improve drug safety and effectiveness in the treatment of minors. The clinical course of youth treated with aripiprazole in the multicentre pharmacovigilance study TDM-VIGIL was systematically followed and serum concentrations measured. Sex, age, weight and comedications were analysed to identify possible effect modifiers. A preliminary therapeutic reference range was estimated for youth with schizophrenia-spectrum disorders, affective disorders and behavioural/emotional/tic disorders coded as treatment responders based on a Clinical-Global Impressions-Improvement (CGI-I) score of much or very much improved. In 93 youth (mean age = 15.2 ± 2.6, range = 7.4-18.2 years, females = 53%, CGI-Severity = 4.4 ± 1.1, responders = 64%), a positive, moderate correlation between the weight-normalized daily dose (WNDD) and aripiprazole serum concentration (=0.791, p < 0.0001) was found. The WNDD and co-medications that interact with CYP2D6 and CYP3A4 affected aripiprazole serum levels, explaining 64% of the variance. In patients within the preliminary therapeutic ranges determined by interquartile ranges (IQRs), slightly better outcomes and fewer adverse drug reactions were found versus patients within preliminary therapeutic ranges determined by the mean ± SD. The preliminary reference range for paediatric patients with schizophrenia-spectrum disorders calculated by the IQR showed an identical lower threshold (100-230 ng/ml) compared to adult schizophrenia-spectrum disorders patients (100-350 ng/ml). The preliminary therapeutic ranges for patients with affective disorders was: 60-160 ng/ml and for patients with behavioural/tic disorders 60-140 ng/ml. The therapeutic reference ranges for aripiprazole in youth estimated via the 25th and 75th IQRs may result in more clinically relevant therapeutic windows. Further studies need to confirm these results, especially in patients with affective and behavioural/tic disorder diagnoses.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Grasping the big picture: impact analysis of screening tools for timely referral for device-aided therapies.","authors":"H R Moes, H S Dafsari, W H Jost, N Kovacs, Z Pirtošek, T Henriksen, C Falup-Pecurariu, M Minár, E Buskens, T van Laar","doi":"10.1007/s00702-024-02783-1","DOIUrl":"10.1007/s00702-024-02783-1","url":null,"abstract":"<p><p>Several screening tools are available to assist general neurologists in the timely identification of patients with advanced Parkinson's disease (PD) who may be eligible for referral for a device-aided therapy (DAT). However, it should be noted that not all of these clinical decision rules have been developed and validated in a thorough and consistent manner. Furthermore, only a limited number of head-to-head comparisons have been performed. Available studies suggest that D-DATS has a higher positive predictive value and higher specificity than the 5-2-1 criteria, while the sensitivity of both screening tools is similar. However, unanswered questions remain regarding the validity of the decision rules, such as whether the diagnostic performance measures from validation studies are generalizable to other populations. Ultimately, the question is whether a screening tool will effectively and efficiently improve the quality of life of patients with PD. To address this key question, an impact analysis should be performed. The authors intend to set up a multinational cluster randomised controlled trial to compare the D-DATS and 5-2-1 criteria on the downstream consequences of implementing these screening tools, with a particular focus on the impact on disability and quality of life.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"1295-1305"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monotherapy with infusion therapies - useful or not?","authors":"Petra Bago Rožanković, Anders Johansson, Klivényi Péter, Ivan Milanov, Per Odin","doi":"10.1007/s00702-024-02801-2","DOIUrl":"10.1007/s00702-024-02801-2","url":null,"abstract":"<p><p>Infusion pump-based therapies are an effective treatment option for patients with advanced Parkinson´s disease. Achieving monotherapy with infusion-based therapies could simplify the treatment regimen, provide better medication adherence, reduce adverse events and drug interactions. This review presents the literature data on the efficacy, safety, and achievability of monotherapy with all available infusion-based therapies, including apomorphine, levodopa-carbidopa-intestinal gel (LCIG), levodopa-entacapone-carbidopa intestinal gel (LECIG), and foslevodopa-foscarbidopa (LDp/CDp). In summary, monotherapy is achievable and effective in most patients on intestinal levodopa infusion therapy and in some patients on apomorphine infusion. There is a need for further investigation of monotherapy compared to polytherapy, especially in new pump treatment options (LECIG and LDp/CDp). Future research should reveal which patients on infusion-based therapies could benefit from monotherapy, including identification of potential baseline predictors of achieving monotherapy in patients treated with specific infusion-based therapies.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"1341-1348"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}