{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T03:08:46Z","timestamp":1779073726789,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sertraline is commonly used to treat mental health conditions in youth. However, its tolerability and efficacy vary between individuals, partly due to interindividual differences in drug metabolism. This study assessed the individual and combined impact of genetic variation in cytochrome P450 drug\u2010metabolizing enzymes on patient\u2010reported side effects and symptom improvement in 347 youth, aged 6\u201324, receiving sertraline treatment. Participants reported sertraline dose, duration, adherence, concomitant medications, side effects, and symptom improvement. DNA was extracted from saliva samples and genotyped for\n                    <jats:italic>CYP2B6<\/jats:italic>\n                    ,\n                    <jats:italic>CYP2C9<\/jats:italic>\n                    ,\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    ,\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    , and\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    . Individual activity scores and a weighted combinatorial\n                    <jats:italic>CYP450<\/jats:italic>\n                    activity score were created. Binomial logistic regression models were used to assess the impact individual and combined\n                    <jats:italic>CYP450<\/jats:italic>\n                    activity scores had on patient\u2010reported side effects and symptom improvement, both with and without correction for phenoconversion. After adjusting for phenoconversion, other CYP450 activity scores, and covariates, higher activity scores for\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    (OR\u2009=\u20090.288, 95% CI\u2009=\u20090.091\u20130.913) and\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    (OR\u2009=\u20090.002, 95% CI\u2009=\u20090.001\u20130.375) were nominally associated with reduced odds of symptom improvement. A higher combined CYP450 activity score was associated with reduced odds of symptom improvement (OR\u2009=\u20090.060, 95% CI\u2009=\u20090.004\u20130.797) and side effects (OR\u2009=\u20090.097, 95% CI\u2009=\u20090.010\u20130.925). These findings suggest that a combined CYP450 activity score may serve as a marker of symptom improvement and side effects in youth, but validation using sertraline\/desmethylsertraline concentrations is required. If validated, these results may inform updates to pharmacogenetic prescribing guidelines for sertraline and support more personalized sertraline use in youth.\n                  <\/jats:p>","DOI":"10.1111\/cts.70590","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T03:50:47Z","timestamp":1778557847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Individual and Combined Cytochrome\n                    <scp>P450<\/scp>\n                    Activity Scores on Symptom Improvement and Side Effects in Youth Treated With Sertraline"],"prefix":"10.1111","volume":"19","author":[{"given":"Samuel","family":"Gerlach","sequence":"first","affiliation":[{"name":"Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7438-4551","authenticated-orcid":false,"given":"Abdullah Al","family":"Maruf","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Rady Faculty of Health Sciences University of Manitoba  Winnipeg Manitoba Canada"},{"name":"Children's Hospital Research Institute of Manitoba  Winnipeg Manitoba Canada"},{"name":"The Mathison Centre for Mental Health Research &amp; Education, Hotchkiss Brain Institute, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Department of Psychiatry University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8551-4530","authenticated-orcid":false,"given":"Sarker M.","family":"Shaheen","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education, Hotchkiss Brain Institute, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Department of Psychiatry University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryden","family":"McCloud","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education, Hotchkiss Brain Institute, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6268-8495","authenticated-orcid":false,"given":"Madison","family":"Heintz","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education, Hotchkiss Brain Institute, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Department of Medical Genetics University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3663-5019","authenticated-orcid":false,"given":"Laina","family":"McAusland","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education, Hotchkiss Brain Institute, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Department of Psychiatry University of Calgary  Calgary Alberta Canada"},{"name":"Department of Medical Genetics University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-4624","authenticated-orcid":false,"given":"Paul D.","family":"Arnold","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education, Hotchkiss Brain Institute, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Department of Psychiatry University of Calgary  Calgary Alberta Canada"},{"name":"Department of Medical Genetics University of Calgary  Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-8696","authenticated-orcid":false,"given":"Chad A.","family":"Bousman","sequence":"additional","affiliation":[{"name":"The Mathison Centre for Mental Health Research &amp; Education, Hotchkiss Brain Institute, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Department of Psychiatry University of Calgary  Calgary Alberta Canada"},{"name":"Department of Medical Genetics University of Calgary  Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute University of Calgary  Calgary Alberta Canada"},{"name":"Department of Physiology &amp; Pharmacology University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Food and Drug Administration \u201cZOLOFT (Sertraline Hydrochloride) Tablets and Oral Solution Label: Highlights of Prescribing Information \u201d(2023) U.S. Food and Drug Administration Silver Spring MD https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/019839s102 020990s059lbl.pdf."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0706743716659276"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2020.05.005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-200110000-00011"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.16.1969"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hup.969"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.752"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-9556(24)15222-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199912000-00001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000392"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-019-0554-x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3707"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11096-016-0259-8"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00023.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2021.114354"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2014.85"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2020.113649"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12938"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2903"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-004-0766-8"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208"},{"issue":"7","key":"e_1_2_9_23_1","first-page":"28","article-title":"The Clinical Global Impressions Scale","volume":"4","author":"Busner J.","year":"2007","journal-title":"Psychiatry (Edgmont)"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12692"},{"key":"e_1_2_9_25_1","unstructured":"PharmGKB \u201cThe Evolution of PharmGKB + CPIC \u201dhttps:\/\/www.pharmgkb.org\/."},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1275"},{"key":"e_1_2_9_27_1","unstructured":"PharmGKB \u201cCuration of DPWG Content Into PharmGKB \u201dhttps:\/\/www.pharmgkb.org\/page\/dpwgMapping."},{"key":"e_1_2_9_28_1","unstructured":"IU School of Medicine \u201cDrug Interaction Flockhart Table \u201d Clinical Pharmacology https:\/\/medicine.iu.edu\/internal\u2010medicine\/specialties\/clinical\u2010pharmacology\/drug\u2010interaction\u2010flockhart\u2010table."},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.636650"},{"key":"e_1_2_9_30_1","unstructured":"\u201cEPIDIOLEX (Cannabidiol) Oral Solution\u201d."},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15070870"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.002428"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70590","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70590","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70590","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T02:58:42Z","timestamp":1779073122000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":31,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/cts.70590"],"URL":"https:\/\/doi.org\/10.1111\/cts.70590","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70590"}}