{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:20:28Z","timestamp":1792153228472,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T00:00:00Z","timestamp":1487548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Heinz C. Prechter Bipolar Research Fund"},{"name":"Richard Tam Foundation"},{"name":"University of Michigan Depression Center"},{"DOI":"10.13039\/100000025","name":"National Institute for Mental Health","doi-asserted-by":"crossref","award":["R01MH082784"],"award-info":[{"award-number":["R01MH082784"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The atypical antipsychotic (<jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content>) class is often associated with metabolic disease, but the mechanistic underpinnings of this risk are not understood. Due to reports linking gut bacteria function to metabolic disease, we hypothesize that <jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content> treatment in adults results in gut dysbiosis potentiating metabolic criteria. This report describes recent findings linking <jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content> treatment with differences in gut microbiota communities in a human cohort with bipolar disorder (<jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a cross\u2010sectional design, we obtained 16S ribosomal sequences from 117 <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content> patients (49 AAP treated, 68 non\u2010<jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content> treated). Analysis of molecular variance (<jats:styled-content style=\"fixed-case\">AMOVA<\/jats:styled-content>) was used to detect significant clustering of microbial communities between groups, and the inverse Simpson Diversity Index was used to calculate alpha diversity. Detection of differentially abundant operational taxonomic units (<jats:styled-content style=\"fixed-case\">OTU<\/jats:styled-content>s) between groups was performed using linear discriminant analysis effect size.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content>\u2010treated cohort was significantly younger and had an increased <jats:styled-content style=\"fixed-case\">body mass index<\/jats:styled-content> compared with non\u2010<jats:styled-content style=\"fixed-case\">AAP\u2010<\/jats:styled-content>treated patients. Groups did not differ in other psychotropic medication use with the exception of higher use of benzodiazepines in the <jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content> cohort. We detected significant separation between microbiota communities of <jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content>\u2010treated and nontreated patients (<jats:styled-content style=\"fixed-case\">AMOVA<\/jats:styled-content>; p=0.04). <jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content>\u2010treated females showed significant decreased species diversity when compared with non\u2010AAP\u2010treated females (p=0.015). Males showed no significant diversity between treatment groups (p=0.8). Differentially abundant <jats:styled-content style=\"fixed-case\">OTU<\/jats:styled-content>s between treatment groups were <jats:styled-content style=\"fixed-case\">OTU<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">OTU<\/jats:styled-content>25, and <jats:styled-content style=\"fixed-case\">OTU<\/jats:styled-content>32 that classified to <jats:italic>Lachnospiraceae<\/jats:italic>,<jats:italic> Akkermansia,<\/jats:italic> and <jats:italic>Sutterella,<\/jats:italic> respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that <jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content> treatment is associated with specific representation of gut bacterial families in <jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content>\u2010treated patients. In addition, <jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content> treatment is associated with decreased species richness in female <jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content>\u2010treated patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1890","type":"journal-article","created":{"date-parts":[[2016,12,30]],"date-time":"2016-12-30T02:42:44Z","timestamp":1483065764000},"page":"261-267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":234,"title":["Interaction Between Atypical Antipsychotics and the Gut Microbiome in a Bipolar Disease Cohort"],"prefix":"10.1002","volume":"37","author":[{"given":"Stephanie A.","family":"Flowers","sequence":"first","affiliation":[{"name":"College of Pharmacy University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen M.","family":"Ward","sequence":"additional","affiliation":[{"name":"College of Pharmacy University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melvin G.","family":"McInnis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki L.","family":"Ellingrod","sequence":"additional","affiliation":[{"name":"College of Pharmacy University of Michigan Ann Arbor Michigan"},{"name":"Department of Psychiatry University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,20]]},"reference":[{"issue":"2","key":"e_1_2_6_2_1","first-page":"A42","article-title":"Congruencies in increased mortality rates, years 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