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This study aimed to elucidate the inflammatory and physiological responses in relation to natural (non-skin) and skin-related trypophobic images.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>Fifty participants (<jats:italic>n<\/jats:italic> = 50) were recruited for the study, and their sensitivity to trypophobia was measured using the trypophobia questionnaire. Then, participants were randomly assigned to either the skin related or non-skin related visual exposure group and viewed trypophobic\u00a0images from a computer screen. Blood samples were collected pre- and post-exposure to trypophobic images and analyzed for IL-6 and TNF-\u03b1 using ELISA and RT-qPCR methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL-6 and TNF-\u03b1 protein levels significantly increased post-exposure, with IL-6 changes varying by stimulus type. mRNA expression showed significant interaction with participants' trypophobia sensitivity scores, suggesting post-transcriptional mechanisms. Heart rate variability (HRV) and heart rate were measured before, during, and after exposure using photoplethysmography. Significant changes in HRV metrics, influenced by stimulus type and trypophobia sensitivity, indicated increased sympathetic and decreased parasympathetic nervous system activity during and after exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings highlight the role of physiological and inflammatory responses in trypophobia, suggesting immune activation and autonomic nervous system involvement based on stimulus type and individual sensitivity. These findings not only contribute to phobia literature but also shed light on the physiological and immunological changes that take place in the bodies of individuals with high sensitivity to trypophobia.<\/jats:p><\/jats:sec>","DOI":"10.1556\/2060.2025.00678","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T14:25:07Z","timestamp":1759155907000},"page":"248-265","update-policy":"https:\/\/doi.org\/10.1556\/policypage.crossmark.crossref.2","source":"Crossref","is-referenced-by-count":1,"title":["Physiological and inflammatory changes to\u00a0natural\u00a0and skin-related trypophobic images"],"prefix":"10.1556","volume":"112","author":[{"given":"Hasan","family":"Kazdagli","sequence":"first","affiliation":[{"name":"Vocational School of Health Sciences, Izmir University of Economics, Izmir, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Baris","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Izmir University of Economics, \u0130zmir, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arda","family":"Kipcak","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Virginia, Charlottesville, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suleyman","family":"Ozturk","sequence":"additional","affiliation":[{"name":"Department of General Psychology, University of Padova, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Ceylan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic, Rochester, USA"},{"name":"Department of Psychiatry, School of Medicine, Ko\u00e7 University, Istanbul, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse Banu","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, \u0130zmir University of Economics, \u0130zmir, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5517-5022","authenticated-orcid":true,"given":"Burak","family":"Erdeniz","sequence":"additional","affiliation":[{"name":"Department of Psychology, Izmir University of Economics, \u0130zmir, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"425","reference":[{"issue":"10","key":"B1","series-title":"Psychol Sci","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1177\/0956797613484937","article-title":"Fear of holes","volume":"24","author":"Cole GG","year":"2013","unstructured":"Cole GG, Wilkins AJ. 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