medRxiv : the preprint server for health sciences最新文献

{"title":"Kinematic Correlates of Early Speech Motor Changes in Cognitively Intact APOE-ε4 Carriers: A Preliminary Study Using a Color-Word Interference Task.","authors":"Mehrdad Dadgostar, Lindsay C Hanford, Jordan R Green, Brian D Richburg, Averi Taylor Cannon, Nelson Barnett, David H Salat, Steven E Arnold, Marziye Eshghi","doi":"10.1101/2025.06.17.25329713","DOIUrl":"https://doi.org/10.1101/2025.06.17.25329713","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most prevalent form of dementia and a major public health challenge. In the absence of a cure, accurate and innovative early diagnostic methods are essential for proactive life and healthcare planning. Speech metrics have shown promising potential for identifying individuals with mild cognitive impairment (MCI) and AD, prompting investigation into whether speech motor features can detect elevated risk even prior to cognitive decline. This study examined whether speech kinematic features measured during a color-word interference task could distinguish cognitively normal APOE-ε4 carriers (E4+) from non-carriers (E4-). Lip movement properties were extracted across pre-, during-, and post-interference sentence segments. Descriptive statistics and independent t-tests were conducted to examine group-level trends in lip movement duration, average speed, and range. Although no group differences reached statistical significance, several features showed moderate effect sizes, suggesting potential neuromotor differences. A support vector machine model with a degree-2 polynomial kernel achieved 87.5% accuracy in classifying APOE-ε4 status using three features: lip movement duration prior to interference, average lip speed during interference, and the change in lip movement range from pre- to during-interference segments. These features reflect subtle differences between the two groups in baseline motor planning, susceptibility to cognitive-motor interference, and articulatory adaptability. The model's high precision (88.90%), sensitivity (88.90%), and specificity (85.70%) underscore the potential clinical utility of speech kinematics for early risk identification. These findings support the use of non-invasive, low-burden speech analysis as a promising digital biomarker for AD risk in cognitively intact individuals and highlight its potential for scalable, remote screening and longitudinal monitoring in diverse populations.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532233","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":"FUS Mislocalization Rewires a Cortical Gene Network to Drive Cognitive and Behavioral Impairment in ALS.","authors":"Raphaelle Cassel, Félicie Lorenc, Aurélie Bombardier, Claudia DE Tapia, Stéphane Dieterle, Cláudio Gouveia Roque, Christopher A Jackson, Geoffrey Stuart-Lopez, Caroline Rouaux, Simon J Guillot, Marie-Christine Birling, Pascal Kessler, Maurizio Grassano, Bryan Traynor, Adriano Chio, Raju Roy, James Shorter, Fergal M Waldron, Jenna M Gregory, Hemali Phatnani, Luc Dupuis, Salim Megat","doi":"10.1101/2025.06.16.25329673","DOIUrl":"10.1101/2025.06.16.25329673","url":null,"abstract":"<p><p>Cognitive and behavioral impairment affects up to half of individuals with amyotrophic lateral sclerosis (ALS), but their molecular origin remains unresolved. Here, we identify mislocalization of the RNA-binding protein FUS in cortical neurons as a defining feature in ALS patients with cognitive impairment (ALS-ci). Selective mislocalization of FUS in adult cortical projection neurons in mice is sufficient to trigger ALS-ci- and ALS with behavioral impairment (ALS-bi)-like phenotypes, including deficits in sociability, and neurodegeneration. Single-nucleus transcriptomics reveal a conserved FUS-dependent gene network downregulated in these mice and ALS-ci patients. This regulon is enriched for ALS genetic risk factors and newly implicates <i>FBXO16</i> in ALS-bi. Carriers of protein-truncating <i>FBXO16</i> variants display behavioral abnormalities, frontotemporal atrophy, and increased levels of dementia-linked biomarkers. These findings define a neuron-intrinsic mechanism for cognitive and behavioral dysfunction in ALS and nominate FUS mislocalization and its downstream gene network as therapeutic targets.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532272","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":"Rural Medical Centers Struggle to Produce Well-Calibrated Clinical Prediction Models: Data Augmentation Can Help.","authors":"Katherine E Brown, Bradley A Malin, Sharon E Davis","doi":"10.1101/2025.06.16.25329699","DOIUrl":"10.1101/2025.06.16.25329699","url":null,"abstract":"<p><p>Machine learning models support many clinical tasks; however, challenges arise with the transportability of these models across a network of healthcare sites. While there are guidelines for updating models to account for local context, we hypothesize that not all healthcare organizations, especially those in smaller and rural communities, have the necessary patient volumes to facilitate local fine tuning to ensure models are reliable for their populations. To investigate these challenges, we conducted an experiment using data from a real network of hospitals to predict 30-day unplanned hospital readmission and a simulation study using data from a multi-site ICU dataset to evaluate the utility of synthetic data generation (SDG) to augment local data volumes. Several factors associated with rurality were correlated with model miscalibration and rural sites failed to meet sample size requirements for local recalibration. Our results indicate that deep learning approaches to SDG produced the best local classifiers.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532327","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":"Circulating gut microbial metabolites and risk of coronary heart disease: a prospective, multi-stage study.","authors":"Danxia Yu, Yulu Zheng, Jae Jeong Yang, Deepak K Gupta, David M Herrington, Bing Yu, Ngoc Quynh H Nguyen, Rui Pinto, Ioanna Tzoulaki, Hui Cai, Qiuyin Cai, Loren Lipworth, Xiao-Ou Shu, Wei Zheng","doi":"10.1101/2025.06.16.25329214","DOIUrl":"https://doi.org/10.1101/2025.06.16.25329214","url":null,"abstract":"<p><strong>Background: </strong>Despite growing evidence linking gut microbiota and microbial metabolites to human cardiometabolic health, few studies have systematically examined circulating microbial metabolites with incident coronary heart disease (CHD).</p><p><strong>Methods: </strong>We conducted a multi-stage metabolomics study involving five prospective cohorts. Discovery involved an untargeted plasma metabolite profiling among 896 incident cases and 896 age-/sex-/race-matched controls (∼300 pairs per race: Black, White, Asian) from the Southern Community Cohort Study (SCCS) and Shanghai Women's Health Study and Shanghai Men's Health Study (SWHS/SMHS). In-silico validation was conducted in the Atherosclerosis Risk in Communities Study (ARIC; N=3539; 663 cases) and Multi-Ethnic Study of Atherosclerosis (MESA; N=3860; 446 cases). Last, a quantitative assay was developed and applied to a new set of 864 cases and 864 age-/sex-/race-matched controls (∼260-340 pairs per race) from SCCS and SWHS/SMHS. Conditional logistic regression estimated odds ratios (ORs) of incident CHD per standard deviation (SD) increase in metabolite levels for discovery and quantitative stages with a nested case-control design. Cox regression was used in ARIC and MESA with a cohort design. All stages were adjusted for similar covariates.</p><p><strong>Results: </strong>The discovery stage identified 73 circulating microbiota-related metabolites associated with incident CHD (FDR<0.10). Sixty-one metabolites were available for in-silico validation, with 24 showing a significant association (p<0.05) in the same direction as discovery. The targeted assay quantified eight of these 24 metabolites, with five significantly associated with incident CHD: imidazole propionate, 3-hydroxy-2-ethylpropionate, 4-hydroxyphenylacetate, trans-4-hydroxyproline, and 3-hydroxybutyrate; OR per SD ranged from 1.18 to 1.27 after adjusting for sociodemographic and lifestyle factors. The targeted assay measured eight other promising microbial metabolites, four of which were significant: trimethylamine N-oxide, phenylacetyl-L-glutamine, 4-hydroxyhippuric acid, and indolepropionate. Most associations were consistent across participant subgroups, although some (e.g., 4-hydroxyphenylacetate) were stronger among Black than White/Asian participants. Other effect modifications were found by age, obesity, and hypertension history.</p><p><strong>Conclusions and relevance: </strong>We identified and validated circulating gut microbial metabolites associated with incident CHD across diverse populations. Our findings offer novel epidemiological evidence on the importance of gut microbial metabolism in CHD development and highlight specific metabolites to prioritize for mechanistic investigation, biomarker validation, and therapeutic development.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532286","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":"Evaluation of Machine Learning-Based Propensity Score Estimation: A Benchmarking Observational Analysis Against a Randomized Trial.","authors":"Kaicheng Wang, Lindsey A Rosman, Haidong Lu","doi":"10.1101/2025.06.16.25329708","DOIUrl":"https://doi.org/10.1101/2025.06.16.25329708","url":null,"abstract":"<p><p>Machine learning (ML) approaches for propensity score estimation are increasingly used with the expectation of improving covariate balance and reducing bias, but their validity in selecting appropriate confounders remains controversial. In this study, we estimated the effectiveness of sacubitril/valsartan versus angiotensin-converting enzyme inhibitor and angiotensin receptor blocker on all-cause mortality among heart failure patients with implantable cardioverter defibrillators in the U.S. Department of Veterans Affairs from 2016 to 2020. We compared results from traditional logistic regression- and ML-based propensity score methods and benchmarked them against the PARADIGM-HF randomized trial. The estimate from logistic regression with a priori confounder selection (HR = 0.93, 95% CI 0.61 - 1.42; 27-month RR = 0.87, 95% CI 0.59 - 1.21) most closely aligned with the trial result (HR = 0.81; 95% CI 0.61 - 1.06). In contrast, generalized boosting models did not outperform traditional logistic regression, and may amplify bias when combined with a data-driven confounder selection (HR = 0.63, 95% CI 0.31 - 1.30; RR = 0.61, 95% CI 0.33 - 1.04). Our findings suggest that ML-based propensity scores may introduce overadjustment bias and underscore the importance of subject-matter knowledge in causal inference with high-dimensional real-world data.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532299","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":"Unanticipated Global Emergence of Multiple <i>Pneumocystis jirovecii</i> Mutants Selected by Mycophenolic Acid Driving Increasing Outbreaks in Solid Organ Transplant Recipients.","authors":"Liang Ma, Ming Hao, Weizhong Chang, Xilong Deng, Junfeng Sun, Marwan M Azar, Alexia Cusini, Thomas Fehr, Sara Gianella, Norihiko Goto, Jannik Helweg-Larsen, Grace Handley, Cedric Hirzel, Laurence Huang, Regina Konrad, Nicolas J Mueller, Shinichi Oka, Lingai Pan, Li Peng, Andreas A Rostved, Monica Sassi, Andreas Sing, Benjamin Spielman, Laura F Walsh, Yubao Wang, Hirohisa Yazaki, Lizbeth Hedstrom, Tomozumi Imamichi, Joseph A Kovacs","doi":"10.1101/2025.06.17.25328583","DOIUrl":"10.1101/2025.06.17.25328583","url":null,"abstract":"<p><strong>Background: </strong>Classified by the WHO as one of the 19 most dangerous fungal pathogens, <i>Pneumocystis jirovecii</i> has been associated with increasing outbreaks of <i>Pneumocystis</i> pneumonia (PCP) among solid organ transplant (SOT) recipients worldwide. Mycophenolic acid (MPA), an inosine monophosphate dehydrogenase (IMPDH) inhibitor commonly used as an immunosuppressant to prevent organ rejection, is a risk factor for PCP. However, MPA also displays antifungal activity, potentially protecting against PCP, despite not being used to treat it. Therefore the underlying factors driving these outbreaks remain undefined.</p><p><strong>Methods: </strong>In this international multicenter retrospective observational study, <i>P. jirovecii</i> samples were collected from 96 SOT patients (including 94 from nine separate outbreaks and 84 on MPA therapy) and 67 non-transplant controls (none on MPA), between 1986 and 2020 across six countries in Europe, North America and Asia. All samples underwent extensive targeted sequencing of the <i>P. jirovecii</i> inosine monophosphate dehydrogenase (<i>impdh</i>) gene and multiple genetic markers, with selected samples further analyzed for complete mitogenome and restriction fragment length polymorphisms. Computational modeling was employed to predict the effects of IMPDH mutations on protein structure and MPA binding.</p><p><strong>Results: </strong>Six <i>impdh</i> mutations (including one previously reported) were identified, with frequencies of 4-21% each in SOT patients and 0-1% in controls. These mutations were strongly associated with prior MPA exposure and showed marked geographic segregation and temporal shifts. Four mutations were each linked to multiple distinct genotype profiles, representing separate <i>P. jirovecii</i> strains. Structure modeling predicted that these four mutations reduced protein stability and binding affinity to MPA.</p><p><strong>Conclusions: </strong>This study suggests that the widespread use of MPA in SOT recipients has unexpectedly driven the emergence of multiple <i>impdh</i> mutations in <i>P. jirovecii</i>, each presumably arising independently in multiple strains worldwide. These mutations likely confer drug resistance and provide a selective survival advantage to <i>P. jirovecii</i> in SOT recipients exposed to MPA, thereby facilitating transmission and outbreaks. These findings have significant implications for the prevention and clinical management of PCP in SOT recipients, highlighting a rare example of how antimicrobial resistance can emerge through unexpected pathways, transcending conventional antimicrobial use and emphasizing the need for increased vigilance and strategic adaptation in clinical practice.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532285","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":"Machine Learning Models Enhance Prediction of Arrhythmogenic Right Ventricular Cardiomyopathy.","authors":"Kwaku K Quansah, Sean A Murphy, Esther Kwon, Emma Anderson, Richard T Carrick, Cynthia A James, Hugh Calkins, Chulan Kwon","doi":"10.1101/2025.06.16.25329706","DOIUrl":"10.1101/2025.06.16.25329706","url":null,"abstract":"<p><p>Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a leading contributor to sudden cardiac death worldwide, yet its diagnosis remains complex, expensive and time-consuming. Machine-learning (ML) classifiers offer a practical solution by delivering rapid, scalable predictions that can lessen dependence on expert interpretation and speed clinical decision-making. Here, we benchmarked eight ML algorithms for ARVC detection using area-under-the-curve (AUC) and accuracy as primary metrics. Gradient Boosted Trees outperformed all other models, achieving an accuracy of 94.34% after rigorous cross-validation. These results underscore the promise of Gradient Boosted Trees classifier as an effective decision-support tool within the ARVC diagnostic workflow, with potential to streamline evaluation and improve patient outcomes.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532305","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":"Late-onset unexplained epilepsy as a risk factor for cognitive impairment and dementia: Protocol for a multi-center prospective longitudinal observational study (ELUCID).","authors":"Alice D Lam, Emily L Johnson, Rani A Sarkis, Leah J Blank, Tyler E Gaston, Mouhsin M Shafi, Rodrigo Zepeda, Kyle R Pellerin, Nathalie Jette, Douglas N Greve, Lori B Chibnik, Rebecca E Amariglio, Gad A Marshall, M Brandon Westover","doi":"10.1101/2025.06.16.25329698","DOIUrl":"https://doi.org/10.1101/2025.06.16.25329698","url":null,"abstract":"<p><strong>Background: </strong>Late-onset unexplained epilepsy (LoUE), defined as epilepsy onset after age 55 without an obvious cause, is an important risk factor for dementia. Studies have shown that 10-25% of individuals with LoUE develop dementia within three to four years following their first seizure. However, the mechanisms underlying progression from LoUE to dementia remain poorly understood. The goals of the ELUCID study are to identify risk factors associated with development of cognitive decline and dementia in LoUE, and to develop tools to identify patients at high risk for these outcomes and thereby establish a foundation for dementia prevention strategies in this population.</p><p><strong>Methods and analysis: </strong>ELUCID is a multi-center prospective longitudinal observational study that will enroll 600 participants aged 55 or older with LoUE across seven U.S. medical centers. Participants undergo a baseline evaluation that includes a detailed clinical history, cognitive testing, brain MRI, overnight scalp EEG, and blood biomarkers. Participants will be followed at six-month intervals to record cognitive and neurological changes, with the primary outcomes of interest being development of mild cognitive impairment and/or dementia. This study aims to establish LoUE disease subtypes based on biomarkers, cognitive trajectories, and imaging features, and to develop a risk stratification tool for predicting risk for cognitive decline and dementia in patients presenting with LoUE.</p><p><strong>Ethics and dissemination: </strong>ELUCID has obtained IRB approval (# 2023P001566, August 2023), with the MassGeneral Brigham IRB serving as the single IRB of record. All de-identified study data will be made publicly available on completion of the study.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532234","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":"Parity modifies the effect of genetic variants associated with gestational duration and birth weight.","authors":"Karin Ytterberg, Hedvig Sundelin, Julius Juodakis, Marc Vaudel, Elizabeth C Corfield, Ole A Andreassen, Per Magnus, Alexandra Havdahl, Staffan Nilsson, Pål R Njolstad, Stefan Johansson, Bo Jacobsson, Pol Solé-Navais","doi":"10.1101/2025.06.17.25329777","DOIUrl":"https://doi.org/10.1101/2025.06.17.25329777","url":null,"abstract":"<p><p>Gestational duration and birth weight are linked to both short- and long-term adverse health outcomes in mothers and their offspring. Previous genome-wide association studies on these pregnancy outcomes have been successful but have overlooked the number of a mother's previous pregnancies. In this study, we explored if parity (the number of children a mother has previously delivered) modifies the maternal or foetal genetic effect of gestational duration and birth weight (gene × parity interactions) using data from the Norwegian Mother, Father, and Child Cohort Study in up to 58,528 mothers and their offspring. Potential genetic effect differences were investigated by: (1) performing parity-stratified genome-wide association studies, (2) testing SNP × parity interactions, (3) testing the interaction between a polygenic prediction of the traits and parity, and (4) assessing the genetic correlation within each outcome across parity. For both phenotypes, we identified shared and distinct loci for each outcome in terms both of genetic region and number in the parity-stratified genome-wide association studies, and the genetic correlation by parity deviated from one for all outcomes. The strongest evidence of genetic modification effect by parity was found for gestational duration in the maternal genome where genetic effects were stronger in the first pregnancy compared to later pregnancies. For instance, the polygenic prediction of the maternal genome on gestational duration had a significant interaction with parity (p-value interaction = 5 × 10 ^-5 ). The results for birth weight were more uncertain, suggesting that the identified gene × parity interactions is largely limited to gestational duration. In conclusion, our study reveals that parity modifies the genetic effects on gestational duration and highlights the relevance of considering parity in genetic studies on pregnancy outcomes.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532314","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":"Essential information about chronobiology and chronotherapy for the optimal care of people with bipolar disorders: an international expert consensus.","authors":"Jacob J Crouse, Victoria Loblay, Anthony Jorm, Timothy Wong, Zsofi de Haan, Carla Gorban, Mirim Shin, Emiliana Tonini, Chris Aiken, Lauren B Alloy, Kürşat Altinbaş, Serge Beaulieu, Joanne S Carpenter, Bruno Etain, Yuichi Esaki, Jess G Fiedorowicz, Corrado Garbazza, Pierre A Geoffroy, Bartholomeus C M Haarman, Tone E G Henriksen, Maria Paz Hidalgo, Maree L Inder, Raymond W Lam, Helle Ø Madsen, Colleen A McClung, Gunnar Morken, Laura Palagini, James Phelps, Richard J Porter, Aswin Ratheesh, Rixt F Riemersma-Van der Lek, Janusz K Rybakowski, Erika Fh Saunders, Peter F J Schulte, Daniel J Smith, Holly A Swartz, Bryan K Tolliver, Anna Wirz-Justice, Ian B Hickie, John F Gottlieb","doi":"10.1101/2025.06.17.25329750","DOIUrl":"https://doi.org/10.1101/2025.06.17.25329750","url":null,"abstract":"<p><strong>Background: </strong>Circadian dysfunction is involved in the pathophysiology of bipolar disorders (BD), and circadian-based interventions are gaining recognition in their management. Moreover, basic and epidemiologic research has generated findings inspiring circadian-informed self- and clinician-management strategies. Despite these gains, many Clinical Practice Guidelines and clinical training programs have not incorporated this evidence in their recommendations and curricula.</p><p><strong>Aims: </strong>This International Society for Bipolar Disorders (ISBD) Chronobiology and Chronotherapy Task Force position paper reports a Delphi study-based international consensus statement on what is essential for mental health clinicians to know about the chronobiology and chronotherapy of BD.</p><p><strong>Methods: </strong>An initial pool of statements was derived via review of academic and grey literatures. Statements were rated on a 5-point scale (essential; important; don't know/depends; unimportant; should not be included). Consensus was reached when statements were rated as essential or important by ≥80% of experts. Two young persons with lived experience of BD gave feedback on acceptability.</p><p><strong>Results: </strong>Thirty experts from 15 countries in Europe, North and South America, and the Asia Pacific participated (mean age 55.3 years [SD=11.8]; 40% female; 83% psychiatrists; mean clinical and research experience of 26 [SD=10.8] and 22 years [SD=12.6], respectively). Eight-hundred-and-forty-seven ratings occurred across 12 core constructs and three rounds; 470 statements were discarded after one round and 35 were discarded after rerating. Consensus was reached on 342 statements spanning four themes: basic circadian science; circadian health and disruption; chronobiology of BD; and six chronotherapies (e.g., key protocols, outcomes, side effects, risks/contraindications).</p><p><strong>Conclusions: </strong>This position paper summarises an international consensus statement on the essential information about the chronobiology and chronotherapy of BD that is intended to help clinicians optimise their management of individuals with BD. This knowledge is available online ( https://osf.io/agk9y ) and its dissemination is expected to enhance the training and efficacy of clinicians globally.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532297","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}