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Other studies have shown that VmPFC\/rACC <jats:italic>deactivation<\/jats:italic> and <jats:italic>blunted<\/jats:italic> cortisol release to <jats:italic>stress and alcohol cues<\/jats:italic> are predictive of time to relapse and relapse severity. However, no previous study has assessed the relationship between these markers of central and peripheral nervous system dysfunction in AD participants and their potential joint effects on relapse risk. Forty early abstinent, treatment engaged AD patients underwent a laboratory experiment with exposure to neutral, alcohol and stress cues and a separate functional magnetic resonance imaging scan with similar cue exposure. Neutral\u2010relaxed state cort:ACTH ratio was significantly associated with VmPFC hyperreactivity to neutral\u2010relaxing cues, and also with hypoactivation in response to alcohol and stress cues in AD patients. Basal heart rate, neutral cort:ACTH ratio and neutral VmPFC hyperreactivty were each associated with risk of relapse. However, abnormal VmPFC activation and elevated cort:ACTH ratio overlap in predicting risk for relapse, and dysfunctional VmPFC response was the sole significant predictor of odds of relapse in a joint model of relapse risk. These findings suggest that the cort:ACTH ratio may serve as a peripheral marker of VmPFC brain dysfunction, while aberrant VmPFC responses need further evaluation as a potential biomarker of alcohol relapse risk in clinical outcome studies.<\/jats:p>","DOI":"10.1111\/adb.12320","type":"journal-article","created":{"date-parts":[[2015,11,5]],"date-time":"2015-11-05T07:40:50Z","timestamp":1446709250000},"page":"468-478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Peripheral and prefrontal stress system markers and risk of relapse in alcoholism"],"prefix":"10.1111","volume":"22","author":[{"given":"Sara K.","family":"Blaine","sequence":"first","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongju","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajita","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000087581.13912.64"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.11.022"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1584"},{"key":"e_1_2_6_5_1","unstructured":"BlaineSK AnsellEB SinhaR(under review)Cumulative adversity brain structure and risk of psychiatric illness."},{"issue":"11","key":"e_1_2_6_6_1","article-title":"Alcohol effects on stress pathways: impact on craving and relapse risk","volume":"60","author":"Blaine SK","year":"2015","journal-title":"Can J Psychiatry"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.09.007"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.02.008"},{"issue":"175","key":"e_1_2_6_9_1","first-page":"1","article-title":"Cognitive reappraisal and expressive suppression strategies role in the emotion regulation: an overview on their modulatory effects and neural correlates","volume":"8","author":"Cutuli D","year":"2014","journal-title":"Frontiers in systems neuroscience"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02922904"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2010.11.004"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agp060"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.10.047"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1326"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.06.006"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2009.00194.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2008.00136.x"},{"issue":"18","key":"e_1_2_6_18_1","first-page":"1","article-title":"Epigenetic effects of stress and corticosteroids in the brain","volume":"6","author":"Hunter RG","year":"2012","journal-title":"Front Cell Neurosci"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agh107"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-002-1255-3"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.06.012"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.11.008"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.306"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.06.028"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780198565741.003.0013"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.762"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.250"},{"key":"e_1_2_6_28_1","first-page":"432","article-title":"How does stress lead to risk of alcohol relapse? 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