{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T11:34:43Z","timestamp":1781955283147,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic alcohol use increases risk of alcohol withdrawal symptoms (AW) and disrupts stress biology and resilient coping, thereby promoting excessive alcohol intake. Chronic alcohol intake and multiple alcohol detoxifications are known to impair brain medial prefrontal cortex (mPFC) and striatal functioning, regions involved in regulating stress, craving and alcohol intake. In two related studies, we examined whether AW predicts this functional brain pathology and whether Prazosin versus Placebo treatment may reverse these effects. In Study 1, patients with Alcohol Use Disorder (AUD) (<jats:italic>N<\/jats:italic>\u2009=\u200945) with varying AW levels at treatment entry were assessed to examine AW effects on corticostriatal responses to stress, alcohol cue and neutral visual images with functional magnetic resonance imaging (fMRI). In Study 2, 23 AUD patients entering a 12\u2010week randomised controlled trial (RCT) of Prazosin, an alpha1 adrenergic antagonist that decreased withdrawal\u2010related alcohol intake in laboratory animals, participated in two fMRI sessions at pretreatment and also at week 9\u201310 of chronic treatment (Placebo: <jats:italic>N<\/jats:italic>\u2009=\u200913; Prazosin: <jats:italic>N<\/jats:italic>\u00a0=\u00a010) to assess Prazosin treatment effects on alcohol\u2010related cortico\u2010striatal dysfunction. Study 1 results indicated that higher AW predicted greater disruption in brain mPFC and striatal response to stress and alcohol cues (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, family\u2010wise error [FWE] correction) and also subsequently greater heavy drinking days (HDD) in early treatment (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). In Study 2, Prazosin versus Placebo treatment reversed mPFC\u2010striatal dysfunction (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, FWE), which in turn predicted fewer drinking days (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) during the 12\u2010week treatment period. These results indicate that AW is a significant predictor of alcohol\u2010related prefrontal\u2010striatal dysfunction, and Prazosin treatment reversed these effects that in turn contributed to improved alcohol treatment outcomes.<\/jats:p>","DOI":"10.1111\/adb.13116","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T22:56:38Z","timestamp":1638485798000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Alcohol withdrawal symptoms predict corticostriatal dysfunction that is reversed by prazosin treatment in alcohol use disorder"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3012-4349","authenticated-orcid":false,"given":"Rajita","family":"Sinha","sequence":"first","affiliation":[{"name":"Yale Stress Center Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Neuroscience Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0156-7220","authenticated-orcid":false,"given":"Nia","family":"Fogelman","sequence":"additional","affiliation":[{"name":"Yale Stress Center Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8754-7479","authenticated-orcid":false,"given":"Stephanie","family":"Wemm","sequence":"additional","affiliation":[{"name":"Yale Stress Center Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5568-9878","authenticated-orcid":false,"given":"Gustavo","family":"Angarita","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongju","family":"Seo","sequence":"additional","affiliation":[{"name":"Yale Stress Center Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen","family":"Hermes","sequence":"additional","affiliation":[{"name":"Yale Stress Center Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"issue":"736","key":"e_1_2_10_2_1","first-page":"1","article-title":"Alcohol use and burden for 195 countries and territories, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"6","author":"Collaboration G","year":"2018","journal-title":"The Lancet"},{"issue":"1","key":"e_1_2_10_3_1","first-page":"S15","article-title":"The state of pharmacotherapy for the treatment of alcohol dependence","volume":"36","author":"Garbutt JC","year":"2009","journal-title":"J Subst Abuse Treat"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.18091022"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020617"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12669"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1407298"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.04.006"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01628.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.151.2.178"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.07.055"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1116523109"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.01.037"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.77"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0684-15.2015"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.762"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2008.00829.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2007.12.002"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-011-2178-7"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4087"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.17080913"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12926"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0000000000000413"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2020.20050609"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.18101143"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.1989.tb00737.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600965113"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2020.19070703"},{"key":"e_1_2_10_29_1","unstructured":"LangPJ BradleyMM CuthbertBN(2008).International affective picture System (IAPS): Affective ratings of pictures and instruction manual. Technical Report A\u20108. University of Florida Gainesville FL"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-0357-5_3"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e31820465fa"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.07.027"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000067980.18461.33"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852900012797"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(00)00114-2"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2020.0249"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807041106"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(16)00104-8"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.2112"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1441.030"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.04.028"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.13116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/adb.13116","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.13116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T08:43:08Z","timestamp":1705912988000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.13116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,2]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1111\/adb.13116"],"URL":"https:\/\/doi.org\/10.1111\/adb.13116","archive":["Portico"],"relation":{},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,2]]},"assertion":[{"value":"2021-07-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13116"}}