Utilising pupillometry as a biomarker for diagnosing ADHD

Utilising pupillometry as a biomarker for diagnosing ADHD | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Utilising pupillometry as a biomarker for diagnosing ADHD Pranjal Bhatt, Dheeraj Maroju This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4584057/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Neurodivergent conditions, notably Attention-deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD), pose considerable challenges in unraveling their pathophysiology due to intricate genetic underpinnings and diverse symptom presentations. The locus coeruleus-norepinephrine (LC-NE) system, central to noradrenergic signaling crucial for cognitive processes like sustained attention, has emerged as a focal point for understanding these conditions. However, the LC's small size and deep brainstem location pose significant hurdles to its cellular, molecular, and physiological investigation. Given these challenges, this study explores pupillometry as a non-invasive, objective measure of cognitive load reflecting LC-NE activity. The aim is to establish pupillometry as a novel biomarker and potentially an endophenotype for ADHD. Leveraging an elastic-net logistic model alongside meticulous five-fold cross-validation and hyperparameter tuning, our research yields promising evidence for future research, achieving an Area under the Curve (AUC) score of 0.969, accompanied by a precision of 100% and a recall of 86%. These findings underscore the efficacy of pupillometry in discerning dysfunction within the LC-NE system, thereby enabling accurate diagnosis of ADHD in pediatric populations. Biological sciences/Neuroscience/Cognitive neuroscience Biological sciences/Neuroscience/Motivation Biological sciences/Neuroscience/Oculomotor system Health sciences/Neurology/Neurological disorders/Neurodevelopmental disorders Health sciences/Biomarkers/Diagnostic markers Health sciences/Biomarkers/Prognostic markers ADHD Biomarkers Pupillometry in ADHD Diagnosis Endophenotype for ADHD LC-NE System Phasic and Tonic Pupil Responses Full Text Additional Declarations No competing interests reported. Supplementary Files supplementaryfiles.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4584057","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":320808380,"identity":"81522498-4f7c-437e-8b54-bb07bfd91e6b","order_by":0,"name":"Pranjal Bhatt","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFUlEQVRIiWNgGAWjYLACCQYLBgMJEKvinxyIOvCAsBYJkBbGhgNnDhiDtSQQYw9Yy8GWA4kNID4+LebSh589sKiRADKanz/+2HAnfX7Y4YdAW+zkdBuwa7HsSzM3kDgmwWA555hhw8Edz3I33k4zAGpJNjY7gF2LwRkGMwkJNqDDbiQAtZxhzt04OwGk5UDiNpxa2L9JSPwDaUn/2HCwjTndcHb6BwJaeMwkJNtAWnKAtrQdTpCXzsFvi2UPT5mEZJ8Ej+WMnMIZZ86kGW6Qzik4kGCA2y/mPOzbpCW+2ciZS6Rv+FBRYSMvPzt984cPFXZyOL0PxMzAiOdBiByAieMAICnGD8gi8g24VY+CUTAKRsHIBAB0hWSvuhV37wAAAABJRU5ErkJggg==","orcid":"","institution":"University of Chicago","correspondingAuthor":true,"prefix":"","firstName":"Pranjal","middleName":"","lastName":"Bhatt","suffix":""},{"id":320808381,"identity":"2002f098-82d9-4cfe-953d-4304f6b3e29c","order_by":1,"name":"Dheeraj Maroju","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"prefix":"","firstName":"Dheeraj","middleName":"","lastName":"Maroju","suffix":""}],"badges":[],"createdAt":"2024-06-14 21:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4584057/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4584057/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66304695,"identity":"f92b00dc-e9a5-47c1-a35b-90bc8cc9da3e","added_by":"auto","created_at":"2024-10-10 07:17:26","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":788212,"visible":true,"origin":"","legend":"","description":"","filename":"Pupillometery.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4584057/v1_covered_89189fdb-e215-4518-b70a-90c643116005.pdf"},{"id":59521487,"identity":"84e4c4ba-6eba-4492-9b1c-38afebde2fb0","added_by":"auto","created_at":"2024-07-02 19:33:49","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":458705,"visible":true,"origin":"","legend":"","description":"","filename":"supplementaryfiles.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4584057/v1/d25dbb0b54583bd45f87ee18.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Utilising pupillometry as a biomarker for diagnosing ADHD","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ADHD Biomarkers, Pupillometry in ADHD Diagnosis, Endophenotype for ADHD, LC-NE System, Phasic and Tonic Pupil Responses","lastPublishedDoi":"10.21203/rs.3.rs-4584057/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4584057/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eNeurodivergent conditions, notably Attention-deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD), pose considerable challenges in unraveling their pathophysiology due to intricate genetic underpinnings and diverse symptom presentations. 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