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Further, an intronic single nucleotide polymorphism (rs2832407, C A) in the\n                      <jats:italic>GRIK1<\/jats:italic>\n                      gene, which encodes the GluK1 subunit of the excitatory kainate receptor, predicted topiramate\u2019s effectiveness in reducing heavy drinking in a clinical trial. The molecular correlates of\n                      <jats:italic>GRIK1<\/jats:italic>\n                      genotype that may relate to topiramate\u2019s ability to reduce drinking remain unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We differentiated induced pluripotent stem cells (iPSCs) characterized by\n                      <jats:italic>GRIK1<\/jats:italic>\n                      rs2832407 genotype from 8 A\/A and 8 C\/C donors into forebrain\u2010lineage neural cultures. Our differentiation protocol yielded mixed neural cultures enriched for glutamatergic neurons. Basal mRNA expression of the\n                      <jats:italic>GRIK1<\/jats:italic>\n                      locus was examined via quantitative polymerase chain reaction (qPCR). The effects of acute topiramate exposure on excitatory spontaneous synaptic activity were examined via whole\u2010cell patch\u2010clamp electrophysiology. Results were compared and contrasted between iPSC donor genotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Although characterization of the\n                      <jats:italic>GRIK1<\/jats:italic>\n                      locus revealed no effect of rs2832407 genotype on\n                      <jats:italic>GRIK1<\/jats:italic>\n                      isoform mRNA expression, a significant difference was observed on\n                      <jats:italic>GRIK1<\/jats:italic>\n                      antisense\u20102 expression, which was greater in C\/C neural cultures. Differential effects of acute exposure to 5\u00a0\u03bcM topiramate were observed on spontaneous synaptic activity in A\/A versus C\/C neurons, with a smaller reduction in excitatory event frequency observed in C\/C donor neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work highlights the use of iPSC technologies to study pharmacogenetic treatment effects in psychiatric disorders and furthers our understanding of the molecular effects of topiramate exposure in human neural cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.14399","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T14:11:36Z","timestamp":1592921496000},"page":"1561-1570","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Molecular Correlates of Topiramate and\n                    <i>GRIK1<\/i>\n                    rs2832407 Genotype in Pluripotent Stem Cell\u2013Derived Neural Cultures"],"prefix":"10.1111","volume":"44","author":[{"given":"Richard","family":"Lieberman","sequence":"first","affiliation":[{"name":"From the Alcohol Research Center (RL, KC, JC) Department of Psychiatry University of Connecticut School of Medicine Farmington Connecticut USA"},{"name":"Department of Neuroscience (RL, ESL) University of Connecticut School of Medicine Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin P.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry (KPJ) Yale University School of Medicine New Haven Connecticut USA"},{"name":"VA Connecticut Healthcare System (KPJ) West Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlin","family":"Clinton","sequence":"additional","affiliation":[{"name":"From the Alcohol Research Center (RL, KC, JC) Department of Psychiatry University of Connecticut School of Medicine Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric S.","family":"Levine","sequence":"additional","affiliation":[{"name":"Department of Neuroscience (RL, ESL) University of Connecticut School of Medicine Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry R.","family":"Kranzler","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction (HRK) Department of Psychiatry Perelman School of Medicine of the University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"VISN4 MIRECC (HRK) Crescenz VAMC Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3616-0431","authenticated-orcid":false,"given":"Jonathan","family":"Covault","sequence":"additional","affiliation":[{"name":"From the Alcohol 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