biostudies-literatureBodkin JANational Institute of Neurological Disorders and StrokeAnonymous FoundationNIMH NIH HHSNational Heart, Lung, and Blood InstituteNHLBI NIH HHSNational Institutes of HealthNIHNational Institute of General Medical SciencesEllison FoundationTeam DanielNational Human Genome Research Institute/NHLBINHGRI NIH HHSCarmela and Menachem AbrahamNINDS NIH HHSFuller FoundationNIGMS NIH HHS523-535https://www.ebi.ac.uk/biostudies/studies/S-EPMC6745274biostudies-literatureUnknown86(7)<h4>Background</h4>The increased mutational burden for rare structural genomic variants in schizophrenia and other neurodevelopmental disorders has so far not yielded therapies targeting the biological effects of specific mutations. We identified two carriers (mother and son) of a triplication of the gene encoding glycine decarboxylase, GLDC, presumably resulting in reduced availability of the N-methyl-D-aspartate receptor coagonists glycine and D-serine and N-methyl-D-aspartate receptor hypofunction. Both carriers had a diagnosis of a psychotic disorder.<h4>Methods</h4>We carried out two double-blind, placebo-controlled clinical trials of N-methyl-D-aspartate receptor augmentation of psychotropic drug treatment in these two individuals. Glycine was used in the first clinical trial, and D-Biological psychiatryTargeted Treatment of Individuals With Psychosis Carrying a Copy Number Variant Containing a Genomic Triplication of the Glycine Decarboxylase Gene.PMC6745274UM1HG006542R21 MH097470R01 NS058529R21 MH104505R21 MH105732T32 HL079888R01NS058529UM1 HG006542R01 GM106373R35 NS105078U24 MH081810R35NS105078R01GM106373T32HL079888Hebbring SLewandowski KEGoff DCHudson JIGodfrey LJSuckow RFKaufman MJWaldstreicher EAnderson TSiegel AJCarvalho CMBFialkowski AVisscher TBodkin JACoyle JTLupski JRSebat JGrochowski CMWeinshilboum RMalhotra DLevy DLMorgan CJColeman MJOngur DJavitt DCRodriguez SBRujescu DMcCarthy SVuckovic AKirchhoff CRudolph UfalseTargeted Treatment of Individuals With Psychosis Carrying a Copy Number Variant Containing a Genomic Triplication of the Glycine Decarboxylase Gene.<h4>Background</h4>The increased mutational burden for rare structural genomic variants in schizophrenia and other neurodevelopmental disorders has so far not yielded therapies targeting the biological effects of specific mutations. We identified two carriers (mother and son) of a triplication of the gene encoding glycine decarboxylase, GLDC, presumably resulting in reduced availability of the N-methyl-D-aspartate receptor coagonists glycine and D-serine and N-methyl-D-aspartate receptor hypofunction. Both carriers had a diagnosis of a psychotic disorder.<h4>Methods</h4>We carried out two double-blind, placebo-controlled clinical trials of N-methyl-D-aspartate receptor augmentation of psychotropic drug treatment in these two individuals. Glycine was used in the first clinical trial, and D-2019-01-01T00:00:00Z2019 Oct2025-06-01T02:33:07.325Z2020-10-08T07:14:02ZS-EPMC67452743127953410.1016/j.biopsych.2019.04.031