{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T10:05:59Z","timestamp":1779271559977,"version":"3.51.4"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Polish National Centre for Research and Development","award":["POIG.01.04.00-04-219\/12"],"award-info":[{"award-number":["POIG.01.04.00-04-219\/12"]}]},{"DOI":"10.13039\/100007771","name":"Medical University of Silesia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007771","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharmacol. Rep"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Schizophrenia is a common mental illness whose pathogenesis is still unknown. The vulnerability and stress model in schizophrenia assume that susceptibility to the disease is mainly associated with genes. Of the five symptomatic dimensions of schizophrenia, cognitive impairment appears to be most associated with the pathogenesis of schizophrenia. The aim of the study was to explore whether selected nucleotide variants in <jats:italic>GRIN1<\/jats:italic>, <jats:italic>GRIN2A<\/jats:italic>, and <jats:italic>GRIN2B<\/jats:italic> encoding subunits of the <jats:italic>N<\/jats:italic>-methyl-<jats:sc>d<\/jats:sc>-aspartate receptor (NMDA-R) receptor occur in a selected group of patients with treatment resistant schizophrenia with cognitive impairment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The study included 45 patients diagnosed with super refractory schizophrenia, all with cognitive deficits and chronically psychotic. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The study did not confirm the presence of any of the four selected single-nucleotide variants in <jats:italic>GRIN1<\/jats:italic>, <jats:italic>GRIN2A<\/jats:italic>, and <jats:italic>GRIN2B<\/jats:italic> subunits of NMDA-R in the study group.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Results of the study indicated that the selected single-nucleotide variants are not associated both with resistance to clozapine and the presence of cognitive deficits in<\/jats:p>\n                <jats:p>schizophrenia. It is possible, however, that a more extensive sequencing along with analyzing the expression of these genes may reveal different single-nucleotide variants than those assumed in the study.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s43440-020-00165-4","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T01:03:11Z","timestamp":1602032591000},"page":"309-315","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Selected single-nucleotide variants in GRIN1, GRIN2A, and GRIN2B encoding subunits of the NMDA receptor are not biomarkers of schizophrenia resistant to clozapine: exploratory study"],"prefix":"10.1007","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1665-7344","authenticated-orcid":false,"given":"Marek","family":"Krzystanek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8832-7726","authenticated-orcid":false,"given":"Marek","family":"Asman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9733-7632","authenticated-orcid":false,"given":"Joanna","family":"Witecka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2632-1211","authenticated-orcid":false,"given":"Artur","family":"Pa\u0142asz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7309-0121","authenticated-orcid":false,"given":"Ryszard","family":"Wiaderkiewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"issue":"1","key":"165_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41537-019-0090-z","volume":"6","author":"SG Potkin","year":"2020","unstructured":"Potkin SG, Kane JM, Correll CU, Lindenmayer JP, Agid O, Marder SR, et al. The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research. NPJ Schizophr. 2020;6(1):1.","journal-title":"NPJ Schizophr"},{"key":"165_CR2","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1177\/0706743717718167","volume":"62","author":"D Siskind","year":"2017","unstructured":"Siskind D, Siskind V, Kisely S. Clozapine response rates among people with treatment-resistant schizophrenia: data from a systematic review and meta-analysis. Can J Psychiatry. 2017;62:772\u20137.","journal-title":"Can J Psychiatry"},{"issue":"2","key":"165_CR3","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.gene.2013.09.110","volume":"535","author":"S Singh","year":"2014","unstructured":"Singh S, Kumar A, Agarwal S, Phadke SR, Jaiswal Y. Genetic insight of schizophrenia: past and future perspectives. Gene. 2014;535(2):97\u2013100.","journal-title":"Gene"},{"issue":"7","key":"165_CR4","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1176\/appi.ajp.159.7.1183","volume":"159","author":"R Fuller","year":"2002","unstructured":"Fuller R, Nopoulos P, Arndt S, O'Leary D, Ho BC, Andreasen NC. Longitudinal assessment of premorbid cognitive functioning in patients with schizophrenia through examination of standardized scholastic test performance. Am J Psychiatry. 2002;159(7):1183\u20139.","journal-title":"Am J Psychiatry"},{"issue":"3","key":"165_CR5","doi-asserted-by":"publisher","first-page":"189","DOI":"10.3371\/CSRP.4.3.6","volume":"4","author":"JT Kantrowitz","year":"2010","unstructured":"Kantrowitz JT, Javitt DC. Thinking glutamatergically: changing concepts of schizophrenia based upon changing neurochemical models. Clin Schizophr Relat Psychoses. 2010;4(3):189\u2013200.","journal-title":"Clin Schizophr Relat Psychoses"},{"key":"165_CR6","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.euroneuro.2008.06.005","volume":"18","author":"RD Paz","year":"2008","unstructured":"Paz RD, Tardito S, Atzori M, Tseng KY. Glutamatergic dysfunction in schizophrenia: from basic neuroscience to clinical psychopharmacology. Eur Neuropsychopharmacol. 2008;18:773\u201386.","journal-title":"Eur Neuropsychopharmacol"},{"issue":"3","key":"165_CR7","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1124\/mol.109.059865","volume":"77","author":"GJ Marek","year":"2010","unstructured":"Marek GJ, Behl B, Bespalov AY, Gross G, Lee Y, Schoemaker H. Glutamatergic (N-methyl-d-aspartate receptor) hypofrontality in schizophrenia: too little juice or a miswired brain? Mol Pharmacol. 2010;77(3):317\u201326.","journal-title":"Mol Pharmacol"},{"key":"165_CR8","doi-asserted-by":"crossref","unstructured":"Tan HY, Callicott JH, Weinberger DR. Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. Cereb Cortex 2007;17:i171\u2013i181.","DOI":"10.1093\/cercor\/bhm069"},{"key":"165_CR9","first-page":"179","volume":"3\u20134","author":"M Krzystanek","year":"2009","unstructured":"Krzystanek M, Pa\u0142asz A, Krzystanek E, Krupka-Matuszczyk I. NMDA receptor insufficiency in pathogenesis of schizophrenia. Farmakoter Psychiatr Neurol. 2009;3\u20134:179\u201390.","journal-title":"Farmakoter Psychiatr Neurol"},{"issue":"6","key":"165_CR10","doi-asserted-by":"publisher","first-page":"E1442","DOI":"10.3390\/ijms20061442","volume":"20","author":"M Krzystanek","year":"2019","unstructured":"Krzystanek M, Pa\u0142asz A. NMDA receptor model of antipsychotic drug-induced hypofrontality. Int J Mol Sci. 2019;20(6):E1442.","journal-title":"Int J Mol Sci"},{"key":"165_CR11","doi-asserted-by":"publisher","first-page":"24663","DOI":"10.3402\/tdp.v2.24663","volume":"2","author":"AH Changasi","year":"2014","unstructured":"Changasi AH, Shams TA, Pouget JG, M\u00fcller DJ. Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight. Transl Dev Psychiatry. 2014;2:24663.","journal-title":"Transl Dev Psychiatry"},{"issue":"suppl 1","key":"165_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000492332","volume":"5","author":"K Yoshida","year":"2019","unstructured":"Yoshida K, M\u00fcller DJ. Pharmacogenetics of antipsychotic drug treatment: update and clinical implications. Mol Neuropsychiatry. 2019;5(suppl 1):1\u201326.","journal-title":"Mol Neuropsychiatry"},{"issue":"10","key":"165_CR13","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1001\/archpsyc.58.10.965","volume":"58","author":"JM Kane","year":"2001","unstructured":"Kane JM, Marder SR, Schooler NR, Wirshing WC, Umbricht D, Baker RW, et al. Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison. Arch Gen Psychiatry. 2001;58(10):965\u201372.","journal-title":"Arch Gen Psychiatry"},{"issue":"7","key":"165_CR14","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/S0006-3223(02)01783-3","volume":"53","author":"S Begni","year":"2003","unstructured":"Begni S, Moraschi S, Bignotti S, Fumagalli F, Rillosi L, Perez J, et al. Association between the G1001C polymorphism in the GRIN1 gene promoter region and schizophrenia. Biol Psychiatry. 2003;53(7):617\u20139.","journal-title":"Biol Psychiatry"},{"issue":"4","key":"165_CR15","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1159\/000071211","volume":"47","author":"HJ Chiu","year":"2003","unstructured":"Chiu HJ, Wang YC, Liou YJ, Lai IC, Chen JY. Association analysis of the genetic variants of the N-methyl d-aspartate receptor subunit 2b (NR2b) and treatment-refractory schizophrenia in the Chinese. Neuropsychobiology. 2003;47(4):178\u201381.","journal-title":"Neuropsychobiology"},{"issue":"2","key":"165_CR16","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1007\/s12031-008-9148-5","volume":"38","author":"H Galehdari","year":"2009","unstructured":"Galehdari H, Pooryasin A, Foroughmand A, Daneshmand S, Saadat M. Association between the G1001C polymorphism in the GRIN1 gene promoter and schizophrenia in the Iranian population. J Mol Neurosci. 2009;38(2):178\u201381.","journal-title":"J Mol Neurosci"},{"issue":"4","key":"165_CR17","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1097\/00041444-200112000-00007","volume":"11","author":"CJ Hong","year":"2001","unstructured":"Hong CJ, Yu YW, Lin CH, Cheng CY, Tsai SJ. Association analysis for NMDA receptor subunit 2B (GRIN2B) genetic variants and psychopathology and clozapine response in schizophrenia. Psychiatr Genet. 2001;11(4):219\u201322.","journal-title":"Psychiatr Genet"},{"key":"165_CR18","first-page":"11","volume":"9","author":"M Saadat","year":"2010","unstructured":"Saadat M. N-Methyl-d-aspartate receptor NR1 subunit gene (GRIN1) G1001C polymorphism and susceptibility to schizophrenia: a meta-analysis. EXCLI J. 2010;9:11\u20136.","journal-title":"EXCLI J"},{"issue":"4","key":"165_CR19","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.3758\/BRM.41.4.1149","volume":"41","author":"F Faul","year":"2009","unstructured":"Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009;41(4):1149\u201360.","journal-title":"Behav Res Methods"},{"issue":"12","key":"165_CR20","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1002\/humu.23895","volume":"40","author":"J Li","year":"2019","unstructured":"Li J, Zhang J, Tang W, Mizu RK, Kusumoto H, XiangWei W, et al. De novo GRIN variants in NMDA receptor M2 channel pore-forming loop are associated with neurological diseases. Hum Mutat. 2019;40(12):2393\u2013413.","journal-title":"Hum Mutat"},{"issue":"6","key":"165_CR21","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.3390\/ijms20061442","volume":"20","author":"M Krzystanek","year":"2019","unstructured":"Krzystanek M, Pa\u0142asz A. NMDA receptor model of antipsychotic drug-induced hypofrontality. Int J Mol Sci. 2019;20(6):1442.","journal-title":"Int J Mol Sci"}],"container-title":["Pharmacological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-020-00165-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43440-020-00165-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-020-00165-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T09:45:00Z","timestamp":1633513500000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43440-020-00165-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,6]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["165"],"URL":"https:\/\/doi.org\/10.1007\/s43440-020-00165-4","relation":{},"ISSN":["1734-1140","2299-5684"],"issn-type":[{"value":"1734-1140","type":"print"},{"value":"2299-5684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,6]]},"assertion":[{"value":"5 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 September 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}