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A metabolomic distress score (MDS) based on 20 identified metabolites previously predicted risk in older White women. This study expands the approach by adding metabolomic features not yet characterized and builds a revised score (rMDS) from up to 5539 unannotated features using nontargeted LC-MS. Across three cohorts, unknown and known signals improved performance and revealed novel pathways linking distress to health and aging; validation is ongoing.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/integrating-unknown-metabolites-to-optimize-a-metabolomic-distress-score-for-psychological-distress-in-older-women/427049/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/integrating-unknown-metabolites-to-optimize-a-metabolomic-distress-score-for-psychological-distress-in-older-women/427049.png","ImageObject",300,407,{"name":92,"@type":93},"CatatanPagi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What problem does the study address regarding aging and health risk?","Question",{"text":113,"@type":114},"It examines how chronic psychological distress contributes to cardiometabolic risk in aging, focusing on metabolic alterations as a key pathway.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How is the revised metabolomic distress score (rMDS) constructed?",{"text":118,"@type":114},"It incorporates previously uncharacterized metabolomic features by analyzing up to 5539 unannotated LC-MS signals and selecting features via LASSO to derive rMDS.",{"name":120,"@type":111,"acceptedAnswer":121},"What evidence shows rMDS performs better than the original MDS?",{"text":122,"@type":114},"In the Nurses’ Health Study cohort, rMDS had a stronger association with distress than the original MDS, and performance improved by integrating novel signals from selected known and unknown metabolites.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},427049,1790812383,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":8,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":81},962090894170,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","1326 Innovation in Aging, 2025, Vol. 9, No. S2  \nStates, 3. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States, 4. The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, United States  \nChronic distress, including depression and anxiety, contributes significantly to cardiometabolic risk in aging populations, with metabolic alterations acting as a key pathway. We previously developed a metabolomic distress score (MDS) using 20 identified metabolites in older White women, which predicted cardiometabolic risk in aging cohorts. Here, we expand this approach by identifying metabolomic features not yet characterized that are associated with distress and derive a revised score incorporating these features (rMDS) . Assays were conducted atthe Broad Institute using nontargeted liquid chromatography-mass spectrometry methods. We performed agnostic analyses assessing associations between distress and up to 5539 unannotated features among older White women from three cohorts: Nurses’Health Study (N = 540, mean age=64), Women’s Health Initiative Observational Cohort (N=1107; mean age=67), and Multi-Ethnic Study of Atherosclerosis (N = 770; mean age=63) . We selected unknown metabolites and derived an rMDS via the least absolute shrinkage and selection operator (LASSO). We identified 14 features robustly associated with distress across all cohorts (p \u003C 0.1), plus 65 features in the two most recently assayed cohorts. Ongoing biochemical identification has led to 26 new metabolite annotations among the features identified, including cholesteryl esters and zeaxanthin. The revised distress score (rMDS) integrated novel signals from 67 LASSO-selected known and unknown metabolites. In NHS, rMDS was more strongly associated with distress than the MDS (OR=5.15, 95%CI [3.85-7.06] vs. OR = 3 .30, 95%CI [2 .59-4.27]) . Validation of rMDS in independent samples is ongoing. Incorporating previously unidentified metabolomic features greatly enhanced the performance of the metabolomic score, revealing novel pathways linking psychological distress to health and aging.  \nAbstract citation ID: igaf122.4412  \nINTEGRATING UNKNOWN METABOLITES TO  \nOPTIMIZE A METABOLOMIC DISTRESS SCORE FOR  \nPSYCHOLOGICAL DISTRESS IN OLDER WOMEN  \nYiwen Zhu1, Raji Balasubramanian2, Julián Ávila-Pacheco3, Clary Clish3, Jie Yao4, Jerome Rotter4, Laura Kubzansky1, and Susan Hankinson2, 1. Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States, 2. University of Massachusetts Amherst, Amherst, Massachusetts, United","cbCais2LKZzStL4e","https://ap.wps.com/l/cbCais2LKZzStL4e","pdf",1161544,"English","# Integrating unknown metabolites into a revised distress score\n## Study rationale and prior MDS\n## Methods and cohorts\n## Feature selection and score optimization\n## Validation status and implications","[{\"question\":\"What problem does the study address regarding aging and health risk?\",\"answer\":\"It examines how chronic psychological distress contributes to cardiometabolic risk in aging, focusing on metabolic alterations as a key pathway.\"},{\"question\":\"How is the revised metabolomic distress score (rMDS) constructed?\",\"answer\":\"It incorporates previously uncharacterized metabolomic features by analyzing up to 5539 unannotated LC-MS signals and selecting features via LASSO to derive rMDS.\"},{\"question\":\"What evidence shows rMDS performs better than the original MDS?\",\"answer\":\"In the Nurses’ Health Study cohort, rMDS had a stronger association with distress than the original MDS, and performance improved by integrating novel signals from selected known and unknown metabolites.\"}]","INTEGRATING UNKNOWN METABOLITES TO OPTIMIZE A METABOLOMIC DISTRESS SCORE FOR PSYCHOLOGICAL DISTRESS IN OLDER WOMEN | PDF",1790642614]