{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T06:22:57Z","timestamp":1772000577136,"version":"3.50.1"},"reference-count":116,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["P60AA007611"],"award-info":[{"award-number":["P60AA007611"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["T32AA007462"],"award-info":[{"award-number":["T32AA007462"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006976","name":"Lilly Endowment, Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006976","id-type":"DOI","asserted-by":"crossref"}]},{"name":"IBM, Inc."},{"DOI":"10.13039\/100006975","name":"Indiana Clinical and Translational Sciences Institute","doi-asserted-by":"publisher","award":["UM1TR004402"],"award-info":[{"award-number":["UM1TR004402"]}],"id":[{"id":"10.13039\/100006975","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Behavioral Sciences"],"abstract":"<jats:p>Sex differences in stress-induced alcohol-seeking are well documented. The overarching goal of this study is to examine how sex may moderate the relationship between depression and anxiety symptoms and stress-induced alcohol-seeking and to identify mechanisms of this relationship. We explore subjective alcohol responses and the resting-state functional connectivity of the amygdala and the hippocampus, regions implicated in anxiety and depression, as potential sex-dependent mediators. This secondary analysis draws from a recently published trial of 84 adults aged 21 to 55 (54.8% female, mean age = 32, SD = 10.68; 58.3% White, 88.1% non-Hispanic\/Latino) who endorsed moderate-to-heavy alcohol use. All participants completed two counterbalanced intravenous alcohol administration sessions, and 54 completed optional neuroimaging. Generalized anxiety symptoms were significantly associated with greater stress-induced alcohol-seeking in women but not in men. Depression symptoms showed a similar pattern, though the results did not reach statistical significance. Across men and women, blunted state stimulation, but not state anxiety, in response to alcohol was associated with greater stress-induced alcohol-seeking. In men, anxiety symptoms were linked with heightened state stimulation effects, which appeared to buffer against stress-induced alcohol-seeking. State stimulation findings may suggest a possible mechanism for sex differences concerning anxiety pathways to alcohol-seeking. Subjective alcohol responses did not mediate the relationship between depression symptoms and stress-induced alcohol-seeking. Resting-state network connectivity findings identified several potential sex-dependent neural mechanisms that warrant further investigation. Although this study was not originally designed as a direct test of competing subjective response and low-level response to alcohol theoretical models, our findings are consistent with Schuckit\u2019s low level of response to alcohol theory. Our findings showed that blunted stimulation may contribute to stress-induced alcohol-seeking among men. Identifying mechanisms that underlie sex-specific relationships with stress-induced alcohol-seeking can inform the development of tailored intervention approaches, ultimately enhancing treatment efficacy for both men and women.<\/jats:p>","DOI":"10.3390\/bs16020311","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T16:22:55Z","timestamp":1771863775000},"page":"311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-Based Mechanisms of Stress-Induced Alcohol-Seeking"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9966-0409","authenticated-orcid":false,"given":"Anna C. S.","family":"Garrison","sequence":"first","affiliation":[{"name":"Department of Psychology, Indiana University Indianapolis, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6696-6105","authenticated-orcid":false,"given":"Evgeny Jenya","family":"Chumin","sequence":"additional","affiliation":[{"name":"Center for Neuroimaging, Medical Imaging Research Institute, Department of Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Indiana Alzheimer\u2019s Disease Research Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Dzemidzic","sequence":"additional","affiliation":[{"name":"Center for Neuroimaging, Medical Imaging Research Institute, Department of Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8618-7011","authenticated-orcid":false,"given":"Julia L.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Psychology, Indiana University Indianapolis, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Psychology, Indiana University Indianapolis, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2202-2660","authenticated-orcid":false,"given":"Ann E. K.","family":"Kosobud","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Kareken","sequence":"additional","affiliation":[{"name":"Center for Neuroimaging, Medical Imaging Research Institute, Department of Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0708-9514","authenticated-orcid":false,"given":"Martin H.","family":"Plawecki","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1990-8337","authenticated-orcid":false,"given":"Melissa A.","family":"Cyders","sequence":"additional","affiliation":[{"name":"Department of Psychology, Indiana University Indianapolis, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.2174\/0929867323666161202092908","article-title":"Sex differences in alcohol use disorder","volume":"24","author":"Agabio","year":"2017","journal-title":"Current Medicinal Chemistry"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Albert, P. 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