{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:51:17Z","timestamp":1790653877253,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 DA034928"],"award-info":[{"award-number":["R21 DA034928"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23 DA 927734"],"award-info":[{"award-number":["K23 DA 927734"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR000124"],"award-info":[{"award-number":["UL1TR000124"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20 DA 022539"],"award-info":[{"award-number":["P20 DA 022539"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA 020726"],"award-info":[{"award-number":["R01 DA 020726"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA 15179"],"award-info":[{"award-number":["R01 DA 15179"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic methamphetamine use is linked to abnormalities in brain structure, which may reflect neurotoxicity related to metabolism of the drug. As the cytochrome P450 2D6 (CYP2D6) enzyme is central to the metabolism of methamphetamine, genotypic variation in its activity may moderate effects of methamphetamine on brain structure and function. This study explored the relationship between <jats:italic>CYP2D6<\/jats:italic> genotype and measures of brain structure and cognition in methamphetamine users. Based on the function of genetic variants, a CYP2D6 activity score was determined in 82 methamphetamine\u2010dependent (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM\u2010IV] criteria) and 79 healthy\u2010control participants who completed tests of cognitive function (i.e., attention, memory, and executive function); most were also evaluated with structural magnetic resonance imaging (MRI) (66 methamphetamine\u2010dependent and 52 controls). The relationship between CYP2D6 activity score and whole brain cortical thickness differed by group (interaction <jats:italic>p<\/jats:italic> = 0.024), as increasing CYP2D6 activity was associated with thinner cortical thickness in the methamphetamine users (<jats:italic>\u03b2<\/jats:italic> = \u22120.254; <jats:italic>p<\/jats:italic> = 0.035), but not in control subjects (<jats:italic>\u03b2<\/jats:italic> = 0.095; <jats:italic>p<\/jats:italic> = 0.52). Interactions between CYP2D6 activity and group were nonsignificant for hippocampal volume (<jats:italic>p<\/jats:italic>s &gt; 0.05), but both hippocampi showed trends similar to those observed for cortical thickness (negative relationships in methamphetamine users [<jats:italic>p<\/jats:italic>s &lt; 0.05], and no relationships in controls [<jats:italic>p<\/jats:italic>s &gt; 0.50]). Methamphetamine users had lower cognitive scores than control subjects (<jats:italic>p<\/jats:italic> = 0.007), but there was no interaction between CYP2D6 activity score and group on cognition (<jats:italic>p<\/jats:italic> &gt; 0.05). Results suggest that <jats:italic>CYP2D6<\/jats:italic> genotypes linked to higher enzymatic activity may confer risk for methamphetamine\u2010induced deficits in brain structure. The behavioral consequences of these effects are unclear and warrant additional investigation.<\/jats:p>","DOI":"10.1111\/adb.12950","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T02:20:11Z","timestamp":1596766811000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<i>CYP2D6<\/i> genotype may moderate measures of brain structure in methamphetamine users"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0172-8848","authenticated-orcid":false,"given":"Andy C.","family":"Dean","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences UCLA Semel Institute for Neuroscience, David Geffen School of Medicine  Los Angeles California USA"},{"name":"Brain Research Institute, UCLA David Geffen School of Medicine  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika L.","family":"Nurmi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences UCLA Semel Institute for Neuroscience, David Geffen School of Medicine  Los Angeles California USA"},{"name":"Brain Research Institute, UCLA David Geffen School of Medicine  Los Angeles California USA"},{"name":"Department of Mental Health VA Greater Los Angeles Healthcare System  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica M.","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur K.","family":"Cho","sequence":"additional","affiliation":[{"name":"Environmental Health Sciences UCLA Fielding School of Public Health  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Seaman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences UCLA Semel Institute for Neuroscience, David Geffen School of Medicine  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3577-7808","authenticated-orcid":false,"given":"Edythe D.","family":"London","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences UCLA Semel Institute for Neuroscience, David Geffen School of Medicine  Los Angeles California USA"},{"name":"Brain Research Institute, UCLA David Geffen School of Medicine  Los Angeles California USA"},{"name":"Department of Molecular and Medical Pharmacology David Geffen School of Medicine  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00186"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(93)90284-Z"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0b013e32833e7e44"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.179"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(91)90181-A"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1300\/J069v21n01_03"},{"issue":"9","key":"e_1_2_7_8_1","first-page":"1059","article-title":"Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6","volume":"25","author":"Lin LY","year":"1997","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200412000-00013"},{"issue":"6","key":"e_1_2_7_10_1","first-page":"856","article-title":"Pharmacokinetics of oral methamphetamine and effects of repeated daily dosing in humans","volume":"20","author":"Cook CE","year":"1992","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11419-008-0054-x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0379-0738(03)00055-0"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100406"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12692"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/31.1.31"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498258609050244"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2018.05.018"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617710000779"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/15563650.2013.818684"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0065-1"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036213"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0713-04.2004"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2012.02.017"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.15288\/jsad.2010.71.335"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.233"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3765-09.2009"},{"key":"e_1_2_7_27_1","volume-title":"The Structured Clinical Interview for DSM\u2010IV Axis I Disorders (SCID\u2010IP)","author":"First MB","year":"1995"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500035"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2011.11.019"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.2466\/pms.1958.8.3.271"},{"key":"e_1_2_7_31_1","volume-title":"Stroop Color and Word Test: A Manual for Clinical and Experimental Uses","author":"Golden CJ","year":"1978"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.140.3562.56"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3932(67)90015-2"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1037\/0096-1523.10.2.276"},{"key":"e_1_2_7_35_1","volume-title":"Wisconsin Card Sorting Test Manual","author":"Heaton RK","year":"1981"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.97.6.1313"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2012.00037"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2015.03.004"},{"key":"e_1_2_7_39_1","volume-title":"Handbook of Normative Data for Neuropsychological Assessment","author":"Mitrushina M","year":"2005"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.03.032"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00569-X"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhg087"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2011.03433.x"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2859-10.2011"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145705005699"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.01.056"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.8.1461"},{"key":"e_1_2_7_48_1","volume-title":"A Gentle Introduction to Stata","author":"Acock AC","year":"2014"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-003-0029-6"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.58.2.215"},{"issue":"2","key":"e_1_2_7_51_1","first-page":"203","article-title":"Chemical release of dopamine from striatal homogenates: evidence for an exchange diffusion model","volume":"208","author":"Fischer JF","year":"1979","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.172"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(02)00177-8"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2009.09.062"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9232"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200303000-00007"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1081\/DMR-120034000"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2016.04.005"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2010.03066.x"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fadb.12950","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.12950","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/adb.12950","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.12950","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T00:01:45Z","timestamp":1693612905000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.12950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,6]]},"references-count":58,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1111\/adb.12950"],"URL":"https:\/\/doi.org\/10.1111\/adb.12950","archive":["Portico"],"relation":{},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,6]]},"assertion":[{"value":"2020-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12950"}}