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FH+ young adults have blunted stress reactivity, lower cognitive performance and altered frontal white matter microstructure compared to FH\u2212 controls. We hypothesized that family history of AUD\/SUD disrupts neuroendocrine regulation of the immune system in FH+ individuals, resulting in altered blood immune cell composition, inflammation and neurocognitive alterations that, ultimately, increases risk for AUD\/SUD and associated psychopathology. We examined white blood cell (WBC) parameters derived from complete blood counts in FH+ (<jats:italic>n<\/jats:italic>\u00a0=\u200937) and FH\u2212 (<jats:italic>n<\/jats:italic>\u00a0=\u200977) young adults without AUD\/SUD to test if immune system dysregulation is present in FH+ individuals. The total WBC count, number of neutrophils and number of monocytes and associated systemic inflammatory response index (SIRI) were significantly increased in the FH+ group. Further, WBC, neutrophil, monocyte counts and SIRI values were all positively correlated with FH density (number of biological parents and grandparents with AUD\/SUD). These novel data are the first to identify an association between family history of AUD\/SUD and increased circulating leukocytes, which is likely indicative of immune dysregulation in FH+ young adults prior to onset of AUD\/SUD. Additional studies are warranted to characterize the functional relevance of the observed immune cell composition in FH+ individuals, but the notion that inexpensive and widely available blood tests may help identify addiction risk could be transformative.<\/jats:p>","DOI":"10.1111\/adb.70000","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T07:28:32Z","timestamp":1732001312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Increased white blood cell\u00a0in young adults with family histories of alcohol and other substance use disorders"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6478-683X","authenticated-orcid":false,"given":"Mustafa N.","family":"Mithaiwala","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikki S.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dylan H.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie S.","family":"Beehler","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harrison S.","family":"Ballard","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea S.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Vista Life Sciences, Inc  Denver Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Lovallo","sequence":"additional","affiliation":[{"name":"University of Oklahoma Health Sciences Center  Oklahoma City Oklahoma USA"},{"name":"VA Medical Center Hospital  Oklahoma City Oklahoma USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Kochunov","sequence":"additional","affiliation":[{"name":"Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School UT Health Houston  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. 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Murphy VA Hospital South Texas Veterans Health System  San Antonio Texas USA"},{"name":"Department of Pharmacology University of Texas Health Science Center at San Antonio  San Antonio Texas USA"},{"name":"Center for Biomedical Neuroscience University of Texas Health Science Center at San Antonio  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences University of California School of Medicine  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Acheson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006\u20100223"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2013.12.011"},{"key":"e_1_2_11_4_1","first-page":"9","volume-title":"Children of Alcoholics: Critical Perspectives","author":"Russell MA","year":"1990"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.55.11.973"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2017.10.014"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0b013e3283523dcc"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2015.01104"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpsycho.2005.10.009"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22559"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2019.02.005"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.02.025"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.14501"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abrep.2021.100401"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.04.013"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11121824"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.141"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.120.000043"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.09.006"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.07.023"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010021\u201001478\u20105"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001\u2010023\u201001446\u20103"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12031128"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067\u2010022\u201006122\u20101"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/15593258211064744"},{"key":"e_1_2_11_26_1","volume-title":"Structured Clinical Interview for DSM\u20105\u2014Research Version (SCID\u20105 for DSM\u20105, Research Version; 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