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Increased inflammation in the brain has been associated with structural damage. Recent studies have also shown that neurofilament light polypeptide (NfL) is released into the systemic circulation following neuronal damage. Although NfL has thus been proposed as a biomarker for neurodegenerative diseases, its connection to alcohol use disorder has not been explored. For this secondary data analysis, we proposed a conceptual model linking alcohol consumption, the pro\u2010inflammatory cytokine IL\u20106, brain structure, and NfL in heavy drinking participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Of the 182 individuals enrolled in this study, 81 participants had usable data on gray matter (GM) thickness and 80\u00a0had usable data on white matter (WM) diffusivity. A subset of participants had NfL (<jats:italic>n<\/jats:italic>\u00a0=\u00a078) and IL\u20106 (<jats:italic>n<\/jats:italic>\u00a0=\u00a0117) data. An estimate of GM thickness was extracted from middle frontal brain regions using FreeSurfer. Estimated mean WM diffusivity values were extracted from Tract Based Spatial Statistics. NfL and IL\u20106 were measured in blood. Regression models were used to test individual linkages in the conceptual model. Based on significant regression results, we created a simplified conceptual model, which we tested using path analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In regressions, negative relationships emerged between GM and both drinks per drinking day (DPDD) (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.018) and NfL (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.004). A positive relationship emerged between WM diffusivity and DPDD (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.033). IL\u20106 was not significantly associated with alcohol use, GM or WM. The final path model demonstrated adequate fit to the data and showed significant, negative associations between DPDD and middle frontal gyrus (MFG) thickness, and between MFG thickness and NfL, but the association between DPDD and NfL was not significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the first study to show that heavy drinking is associated with lower GM thickness and higher WM diffusivity and that lower GM thickness is associated with higher circulating NfL. The analyses also show that the effects of drinking do not involve the pro\u2010inflammatory cytokine IL\u20106.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14712","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T10:45:14Z","timestamp":1631702714000},"page":"2256-2270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Exploring relationships between alcohol consumption, inflammation, and brain structure in a heavy drinking sample"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1232-1202","authenticated-orcid":false,"given":"Hollis C.","family":"Karoly","sequence":"first","affiliation":[{"name":"Institute for Cognitive Science University of Colorado Boulder Boulder Colorado USA"},{"name":"Department of Psychology Colorado State University Fort Collins Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carillon J.","family":"Skrzynski","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience University of Colorado Boulder Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin N.","family":"Moe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela D.","family":"Bryan","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience University of Colorado Boulder Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent E.","family":"Hutchison","sequence":"additional","affiliation":[{"name":"Institute for Cognitive Science University of Colorado Boulder Boulder Colorado USA"},{"name":"Department of Psychology and Neuroscience University of Colorado Boulder Boulder Colorado USA"},{"name":"Department of Psychiatry University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.08.002"},{"key":"e_1_2_7_3_1","volume-title":"Key substance use and mental health indicators in the United States: Results from the 2016 National Survey on Drug Use and Health","author":"Ahrnsbrak R.","year":"2017"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-8119(03)00336-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.10.019"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.05.018"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2013.10.009"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2012.01920.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106521"},{"key":"e_1_2_7_10_1","first-page":"163","article-title":"Alcohol and gut\u2010derived inflammation","volume":"38","author":"Bishehsari F.","year":"2017","journal-title":"Alcohol Research"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30124-2"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2006.00084.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2006.00084.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1998.0395"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1037\/0893-164X.18.2.184"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12481"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01452.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11432-019-2857-5"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00569-X"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1998.0396"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.05.027"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2003.tb02873.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003680"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2011.12.025"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.06.081"},{"key":"e_1_2_7_26_1","unstructured":"Jorgensen T.D. 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