{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:51:57Z","timestamp":1789901517790,"version":"4.0.1"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T00:00:00Z","timestamp":1506384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["P50 DA037844"],"award-info":[{"award-number":["P50 DA037844"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>Major depressive disorder (MDD) is a complex illness caused by both genetic and environmental factors. Antidepressant resistance also has a genetic component. To date, however, very few genes have been identified for major depression or antidepressant resistance. In this study, we investigated whether outbred heterogeneous stock (HS) rats would be a suitable model to uncover the genetics of depression and its connection to antidepressant resistance. The Wistar Kyoto (WKY) rat, one of the eight founders of the HS, is a recognized animal model of juvenile depression and is resistant to fluoxetine antidepressant treatment. We therefore hypothesized that adolescent HS rats would exhibit variation in both despair\u2010like behavior and response to fluoxetine treatment. We assessed heritability of despair\u2010like behavior and response to sub\u2010acute fluoxetine using a modified forced swim test (FST) in 4\u2010week\u2010old HS rats. We also tested whether blood transcript levels previously identified as depression biomarkers in adolescent human subjects are differentially expressed in HS rats with high vs. low FST immobility. We demonstrate heritability of despair\u2010like behavior in 4\u2010week\u2010old HS rats and show that many HS rats are resistant to fluoxetine treatment. In addition, blood transcript levels of <jats:italic>Amfr, Cdr2<\/jats:italic> and <jats:italic>Kiaa1539,<\/jats:italic> genes previously identified in human adolescents with MDD, are differentially expressed between HS rats with high vs. low immobility. These data demonstrate that FST despair\u2010like behavior will be amenable to genetic fine\u2010mapping in adolescent HS rats. The overlap between human and HS blood biomarkers suggest that these studies may translate to depression in humans.<\/jats:p>","DOI":"10.1111\/gbb.12410","type":"journal-article","created":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T15:06:44Z","timestamp":1503414404000},"page":"139-148","source":"Crossref","is-referenced-by-count":29,"title":["Heterogeneous stock rats: a model to study the genetics of despair\u2010like behavior in adolescence"],"prefix":"10.1111","volume":"17","author":[{"given":"K.","family":"Holl","sequence":"first","affiliation":[{"name":"Department of pediatrics Medical College of Wisconsin  Milwaukee WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"He","sequence":"additional","affiliation":[{"name":"Internal Medicine, Molecular Medicine Wake Forest Baptist Health  Winston Salem NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Wedemeyer","sequence":"additional","affiliation":[{"name":"Department of pediatrics Medical College of Wisconsin  Milwaukee WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Clopton","sequence":"additional","affiliation":[{"name":"Department of pediatrics Medical College of Wisconsin  Milwaukee WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Wert","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9718-0081","authenticated-orcid":false,"given":"J. K.","family":"Meckes","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Cheng","sequence":"additional","affiliation":[{"name":"University of California  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Kastner","sequence":"additional","affiliation":[{"name":"Department of pediatrics Medical College of Wisconsin  Milwaukee WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. A.","family":"Palmer","sequence":"additional","affiliation":[{"name":"University of California  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. E.","family":"Redei","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7943-798X","authenticated-orcid":false,"given":"L. C.","family":"Solberg Woods","sequence":"additional","affiliation":[{"name":"Internal Medicine, Molecular Medicine Wake Forest Baptist Health  Winston Salem NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,26]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-003-2292-x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10519-004-1018-5"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2010.119"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4530(95)00018-6"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2012_224"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2644"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2006.01.007"},{"key":"e_1_2_5_9_1","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1210\/en.2004-0948","article-title":"Quantitative trait loci associated with elevated thyroid\u2010stimulating hormone in the Wistar\u2010Kyoto rat","volume":"146","author":"Baum A.E.","year":"2005","journal-title":"Endocrinology"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2015.47"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.299.8.901"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.15.1683"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2156-12-66"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14659"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(96)01023-2"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2005.03.008"},{"key":"e_1_2_5_17_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ijdevneu.2016.11.003","article-title":"Anxiety\u2010 and depressive\u2010like profiles during early\u2010 and mid\u2010adolescence in the female Wistar Kyoto rat","volume":"56","author":"D'Souza D.","year":"2016","journal-title":"Int J Dev Neurosci"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02245592"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.12.002"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200002280-00038"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/070674371405900202"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(89)80076-2"},{"key":"e_1_2_5_23_1","volume-title":"Econometric Analysis","author":"Green","year":"2000"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(98)00298-4"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1984.tb05706.x"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016646"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3623"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.12.033"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.1.109"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02246177"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01276-4"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.07.029"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(99)00100-1"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2009.03.003"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.28"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12063"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2010.12.015"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.16.2087"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-458-2_7"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.26"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(89)90203-5"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(94)90097-3"},{"issue":"4","key":"e_1_2_5_43_1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.biopsych.2016.05.010","article-title":"Genome\u2010wide association for major depression through age at onset stratification: major depressive disorder working group of the Psychiatric Genomics Consortium","volume":"81","author":"Power R.A.","year":"2016","journal-title":"Biol Psychiatry"},{"key":"e_1_2_5_44_1","first-page":"4","article-title":"Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy","volume":"442","author":"Redei E.E.","year":"2014","journal-title":"Transl Psychiatry"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4530(01)00052-X"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(01)00368-X"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.044"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001255"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-004-2326-z"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00052.2006"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.3.R786"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00127.2013"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-009-9211-8"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00178.2009"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00040.2012"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.157.10.1552"},{"issue":"4","key":"e_1_2_5_57_1","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.biopsych.2016.05.024","article-title":"Using clinical characteristics to identify which patients with major depressive disorder have a higher genetic load for three psychiatric","volume":"81","author":"Verduijn J.","year":"2016","journal-title":"Biol Psychiatry"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30883"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001345"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-4034-7"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008905"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.01.043"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp380"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.222602"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.198"}],"container-title":["Genes, Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fgbb.12410","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/gbb.12410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T14:11:44Z","timestamp":1695651104000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gbb.12410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,26]]},"references-count":64,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/gbb.12410"],"URL":"https:\/\/doi.org\/10.1111\/gbb.12410","archive":["Portico"],"relation":{},"ISSN":["1601-1848","1601-183X"],"issn-type":[{"value":"1601-1848","type":"print"},{"value":"1601-183X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,26]]}}}