Sex differences in response to violence: Role of salience network expansion and connectivity on depression

Sex differences in response to violence: Role of salience network expansion and connectivity on depression | 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 Sex differences in response to violence: Role of salience network expansion and connectivity on depression Ellyn Butler, Noelle Samia, Amanda Mejia, Damon Pham, Adam Pines, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5822551/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Oct, 2025 Read the published version in Translational Psychiatry → Version 1 posted 11 You are reading this latest preprint version Abstract Violence is a major risk factor for depression across development. Depression quickly worsens during early adolescence, however, and especially among females, who experience worse depression following threats than males. This may be because they perceive future threats as less controllable. Evidence suggests that features of the salience network may serve as particularly critical mechanisms explaining sex differences on depression in response to threat, as those with depressive disorders have more expansive salience networks than controls, and threatening experiences result in the brain utilizing more tissue for fear generation in rodent models. Using a longitudinal sample of 220 adolescents ages 14-18 from the Chicago area, we test if salience network expansion and connectivity explain the differential impact of violence on depression across the sexes. We found that the association between violence and depression was greater for females than males (𝛽̂3(2)=0.337, 𝑝=0.025), such that there was a positive association among females, but not males. Contrary to our hypotheses, we found that the association between the expansion of the salience network and depression was positive for males (𝛽̂1(5)=0.242, 𝑝=0.039), as was the association between salience network connectivity and depression (𝛽̂1(6)=0.238, 𝑝=0.030). Both of these effects remained after controlling for depression two years prior, indicating that exposures that impact males’ depression through the salience network likely occur during middle adolescence. Through identifying types of exposures, their relevant developmental timing, and mechanisms connecting exposures with depression, this work helps to inform interventions to prevent the onset of depression following adversity, thereby reducing the lifetime burden of depression. Health sciences/Diseases/Psychiatric disorders/Depression Biological sciences/Neuroscience Biological sciences/Psychology/Human behaviour Full Text Additional Declarations The authors have declared there is NO conflict of interest to disclose Cite Share Download PDF Status: Published Journal Publication published 21 Oct, 2025 Read the published version in Translational Psychiatry → Version 1 posted Editorial decision: revise 20 Mar, 2025 Review # 1 received at journal 25 Feb, 2025 Review # 3 received at journal 21 Feb, 2025 Review # 2 received at journal 10 Feb, 2025 Reviewer # 3 agreed at journal 28 Jan, 2025 Reviewer # 2 agreed at journal 27 Jan, 2025 Reviewer # 1 agreed at journal 27 Jan, 2025 Reviewers invited by journal 26 Jan, 2025 Submission checks completed at journal 15 Jan, 2025 Editor assigned by journal 13 Jan, 2025 First submitted to journal 13 Jan, 2025 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-5822551","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":407339437,"identity":"b1432d75-9eb3-45e4-99ff-c32b8aa8a93f","order_by":0,"name":"Ellyn Butler","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIie3PMYrCQBTG8Xl8S2zGTauIeAUllaziWYLtWniDwEDSRGvFwltYLRgJeImxE1JHbGSx8KlgKjPYCc4fZvIY5kcYIWy2d6yCgPeEB/7kvJyKiYDuREIIml0JXiGQtxODcEFhY/y389fA9tj7X7W+ISg//D4ndcVklmV+DGe4GE11J4RAfb56TtopE5mkTKSHUayJiYNqCRkUxD2iG+uBkbRR/AUQJ+0bSS0l9SOTzItTx6NJoIchSJW+xY3URstk14witRens+4v+SQ/lBDuq/YYKbztQel9Dnkxn02XbTab7RO7AKs4S+F5qQZ9AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-6316-6444","institution":"Northwestern University","correspondingAuthor":true,"prefix":"","firstName":"Ellyn","middleName":"","lastName":"Butler","suffix":""},{"id":407339438,"identity":"776ff93b-305e-4857-a025-4879c0fc2f1a","order_by":1,"name":"Noelle Samia","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Noelle","middleName":"","lastName":"Samia","suffix":""},{"id":407339439,"identity":"f3bf2575-169c-40bd-8f4e-d5116a8432e4","order_by":2,"name":"Amanda Mejia","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Amanda","middleName":"","lastName":"Mejia","suffix":""},{"id":407339440,"identity":"ffd56077-aafc-4cf1-b3be-c7c17793ba87","order_by":3,"name":"Damon Pham","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Damon","middleName":"","lastName":"Pham","suffix":""},{"id":407339441,"identity":"7be84c52-e2ee-4b10-8c58-843b2df85603","order_by":4,"name":"Adam Pines","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Adam","middleName":"","lastName":"Pines","suffix":""},{"id":407339442,"identity":"5b8106e8-4b7f-4014-b0f4-552e99a0bdd2","order_by":5,"name":"Robin Nusslock","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Robin","middleName":"","lastName":"Nusslock","suffix":""}],"badges":[],"createdAt":"2025-01-13 20:45:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5822551/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5822551/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41398-025-03614-x","type":"published","date":"2025-10-21T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":93996641,"identity":"94c1112f-aca3-4a58-a058-98f338750f50","added_by":"auto","created_at":"2025-10-21 07:09:00","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1123276,"visible":true,"origin":"","legend":"","description":"","filename":"saliencenetworkviolencedepression.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5822551/v1_covered_9ef94bce-6e7d-4539-82c4-435bfe9cdf01.pdf"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose","formattedTitle":"Sex differences in response to violence: Role of salience network expansion and connectivity on depression","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"translational-psychiatry","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tp","sideBox":"Learn more about [Translational Psychiatry](http://www.nature.com/tp/)","snPcode":"41398","submissionUrl":"https://mts-tp.nature.com/cgi-bin/main.plex","title":"Translational Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5822551/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5822551/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eViolence is a major risk factor for depression across development. 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