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Research Article

Risperidone Response in Patients with Schizophrenia Drives DNA Methylation Changes in Immune and Neuronal Systems

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Pages 21-38 | Received 16 Jan 2023, Accepted 28 Feb 2023, Published online: 15 Mar 2023

References

  • Charlson FJ , FerrariAJ , SantomauroDFet al. Global epidemiology and burden of schizophrenia: findings from the Global Burden of Disease Study 2016. Schizophr. Bull.44(6), 1195–1203 (2018).
  • Vos T , FlaxmanAD , NaghaviMet al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet Lond. Engl.380(9859), 2163–2196 (2012).
  • Chong HY , TeohSL , WuDB-C , KotirumS , ChiouC-F , ChaiyakunaprukN. Global economic burden of schizophrenia: a systematic review. Neuropsychiatr. Dis. Treat.12, 357–373 (2016).
  • Jääskeläinen E , JuolaP , HirvonenNet al. A systematic review and meta-analysis of recovery in schizophrenia. Schizophr. Bull.39(6), 1296–1306 (2013).
  • Bjornestad J , LavikKO , DavidsonL , HjeltnesA , MoltuC , VesethM. Antipsychotic treatment–a systematic literature review and meta-analysis of qualitative studies. J. Ment. Health29(5), 513–523 (2020).
  • Zhang J-P , GallegoJA , RobinsonDG , MalhotraAK , KaneJM , CorrellCU. Efficacy and safety of individual second-generation vs. first-generation antipsychotics in first-episode psychosis: a systematic review and meta-analysis. Int. J. Neuropsychopharmacol.16(6), 1205–1218 (2013).
  • Cavalcante DA , CoutinhoLS , OrtizBBet al. Impact of duration of untreated psychosis in short-term response to treatment and outcome in antipsychotic naive first-episode psychosis. Early Interv. Psychiatry14(6), 677–683 (2020).
  • Haddad PM , CorrellCU. The acute efficacy of antipsychotics in schizophrenia: a review of recent meta-analyses. Ther. Adv. Psychopharmacol.8(11), 303–318 (2018).
  • Martinuzzi E , BarbosaS , DaoudlarianDet al. Stratification and prediction of remission in first-episode psychosis patients: the OPTiMiSE cohort study. Transl. Psychiatry9(1), 1–13 (2019).
  • Troudet R , AliWBH , Bacq-DaianDet al. Gene expression and response prediction to amisulpride in the OPTiMiSE first episode psychoses. Neuropsychopharmacology45(10), 1637–1644 (2020).
  • García-Gutiérrez MS , NavarreteF , SalaF , GasparyanA , Austrich-OlivaresA , ManzanaresJ. Biomarkers in psychiatry: concept, definition, types and relevance to the clinical reality. Front. Psychiatry11, 432 (2020).
  • Yoshida K , MüllerDJ. Pharmacogenetics of antipsychotic drug treatment: update and clinical implications. Complex Psychiatry5(1), 1–26 (2019).
  • Brennan MD . Pharmacogenetics of second-generation antipsychotics. Pharmacogenomics15(6), 869–884 (2014).
  • Stevenson JM , ReillyJL , HarrisMSHet al. Antipsychotic pharmacogenomics in first episode psychosis: a role for glutamate genes. Transl. Psychiatry6(2), e739–e739 (2016).
  • Ruderfer DM , CharneyAW , ReadheadBet al. Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach. Lancet Psychiatry3(4), 350–357 (2016).
  • Crespo-Facorro B , PrietoC , SainzJ. Schizophrenia gene expression profile reverted to normal levels by antipsychotics. Int. J. Neuropsychopharmacol.18(4), pyu066 (2015).
  • Kumarasinghe N , BeveridgeNJ , GardinerEet al. Gene expression profiling in treatment-naive schizophrenia patients identifies abnormalities in biological pathways involving AKT1 that are corrected by antipsychotic medication. Int. J. Neuropsychopharmacol.16(7), 1483–1503 (2013).
  • Wagh VV , VyasP , AgrawalS , PachporTA , ParalikarV , KhareSP. Peripheral blood-based gene expression studies in schizophrenia: a systematic review. Front. Genet.12, 736483 (2021).
  • Sainz J , PrietoC , Ruso-JulveF , Crespo-FacorroB. Blood gene expression profile predicts response to antipsychotics. Front. Mol. Neurosci.11, 73 (2018).
  • Paziewska A , DabrowskaM , GorycaKet al. DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy. Br. J. Cancer111(4), 781–789 (2014).
  • Smigielski L , JagannathV , RösslerW , WalitzaS , GrünblattE. Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings. Mol. Psychiatry25(8), 1718–1748 (2020).
  • Burghardt KJ , KhouryAS , MsallatyZ , YiZ , SeyoumB. Antipsychotic medications and DNA methylation in schizophrenia and bipolar disorder: a systematic review. Pharmacother. J. Hum. Pharmacol. Drug Ther.40(4), 331–342 (2020).
  • Ovenden ES , McGregorNW , EmsleyRA , WarnichL. DNA methylation and antipsychotic treatment mechanisms in schizophrenia: progress and future directions. Prog. Neuropsychopharmacol. Biol. Psychiatry81, 38–49 (2018).
  • Swathy B , BanerjeeM. Understanding epigenetics of schizophrenia in the backdrop of its antipsychotic drug therapy. Epigenomics9(5), 721–736 (2017).
  • Rukova B , StanevaR , HadjidekovaS , StamenovG , MilanovaV , TonchevaD. Whole genome methylation analyses of schizophrenia patients before and after treatment. Biotechnol. Biotechnol. Equip.28(3), 518–524 (2014).
  • Galanter JM , GignouxCR , OhSSet al. Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures. eLife6, e20532 (2017).
  • Horvath S , RajK. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat. Rev. Genet.19(6), 371–384 (2018).
  • Lieberman JA , StroupTS , McEvoyJPet al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med.353(12), 1209–1223 (2005).
  • Zeilinger S , KühnelB , KloppNet al. Tobacco Smoking leads to extensive genome-wide changes in DNA methylation. PLOS ONE8(5), e63812 (2013).
  • Burghardt KJ , GoodrichJM , LinesBN , EllingrodVL. The influence of metabolic syndrome and sex on the DNA methylome in schizophrenia. Int. J. Genomics2018, e8076397 (2018).
  • Burghardt KJ , PilsnerJR , BlyMJ , EllingrodVL. DNA methylation in schizophrenia subjects: gender and MTHFR 677C/T genotype differences. Epigenomics4(3), 261–268 (2012).
  • Haas M , UnisAS , ArmenterosJ , CopenhaverMD , QuirozJA , KushnerSF. A 6-week, randomized, double-blind, placebo-controlled study of the efficacy and safety of risperidone in adolescents with schizophrenia. J. Child Adolesc. Psychopharmacol.19(6), 611–621 (2009).
  • Moran S , ArribasC , EstellerM. Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences. Epigenomics8(3), 389–399 (2016).
  • R Core Team . R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austriawww.R-project.org/
  • Dedeurwaerder S , DefranceM , BizetM , CalonneE , BontempiG , FuksF. A comprehensive overview of Infinium HumanMethylation450 data processing. Brief. Bioinform.15(6), 929–941 (2014).
  • Heiss JA , JustAC. Identifying mislabeled and contaminated DNA methylation microarray data: an extended quality control toolset with examples from GEO. Clin. Epigenetics10(1), 73 (2018).
  • McCartney DL , WalkerRM , MorrisSW , McIntoshAM , PorteousDJ , EvansKL. Identification of polymorphic and off-target probe binding sites on the Illumina Infinium MethylationEPIC BeadChip. Genomics Data9, 22–24 (2016).
  • Pidsley R , ZotenkoE , PetersTJet al. Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol.17(1), 208 (2016).
  • Teschendorff AE , MarabitaF , LechnerMet al. A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics29(2), 189–196 (2013).
  • Salas L , KoestlerDC. FlowSorted.Blood.EPIC: illumina EPIC data on immunomagnetic sorted peripheral adult blood cells (2020). https://github.com/immunomethylomics/FlowSorted.Blood.EPIC
  • Jaffe AE , IrizarryRA. Accounting for cellular heterogeneity is critical in epigenome-wide association studies. Genome Biol.15(2), R31 (2014).
  • Fortin J-P , LabbeA , LemireMet al. Functional normalization of 450k methylation array data improves replication in large cancer studies. Genome Biol.15(11), 503 (2014).
  • Lê S , JosseJ , HussonF. FactoMineR: an R package for multivariate analysis. J. Stat. Softw.25(1), 1–18 (2008).
  • Maksimovic J , OshlackA , PhipsonB. Gene set enrichment analysis for genome-wide DNA methylation data. Genome Biol.22(1), 173 (2021).
  • Simillion C , LiechtiR , LischerHEL , IoannidisV , BruggmannR. Avoiding the pitfalls of gene set enrichment analysis with SetRank. BMC Bioinformatics18(1), 151 (2017).
  • Alexa A , RahnenführerJ. Gene set enrichment analysis with topGO. https://bioconductor.riken.jp/packages/3.2/bioc/vignettes/topGO/inst/doc/topGO.pdf
  • Manjang K , TripathiS , Yli-HarjaO , DehmerM , Emmert-StreibF. Graph-based exploitation of gene ontology using GOxploreR for scrutinizing biological significance. Sci. Rep.10(1), 16672 (2020).
  • Yu G . Gene ontology semantic similarity analysis using GOSemSim. In: Stem Cell Transcriptional Networks: Methods and Protocols.KidderBL ( Ed.). Springer US, NY, USA, 207–215 (2020).
  • Yu G , LiF , QinY , BoX , WuY , WangS. GOSemSim: an R package for measuring semantic similarity among GO terms and gene products. Bioinformatics26(7), 976–978 (2010).
  • Brooks ME , KristensenK , van BenthemKJet al. glmmTMB balances speed and flexibility among packages for zero-inflated generalized linear mixed modeling. R J.9(2), 378–400 (2017).
  • Hartig F , LohseL. DHARMa: residual diagnostics for hierarchical (multi-level/mixed) regression models (2022). https://CRAN.R-project.org/package=DHARMa
  • Braun P , HanS , NagahamaYet al. 28–IMAGE-CpG: development of a web-based search tool for genome-wide DNA methylation correlation between live human brain and peripheral tissues within individuals. Eur. Neuropsychopharmacol.29, S796 (2019).
  • Bühlmann P , HothornT. Boosting algorithms: regularization, prediction and model fitting. Stat. Sci.22(4), 477–505 (2007).
  • Hofner B , BoccutoL , GökerM. Controlling false discoveries in high-dimensional situations: boosting with stability selection. BMC Bioinformatics16(1), 144 (2015).
  • Sandberg AA , SteenVM , TorsvikA. Is elevated neutrophil count and neutrophil-to-lymphocyte ratio a cause or consequence of schizophrenia?–A scoping review. Front. Psychiatry12, 728990 (2021).
  • van Mierlo HC , BroenJCA , KahnRS , de WitteLD. B-cells and schizophrenia: a promising link or a finding lost in translation?Brain Behav. Immun.81, 52–62 (2019).
  • Miller BJ , GoldsmithDR. Inflammatory biomarkers in schizophrenia: implications for heterogeneity and neurobiology. Biomark. Neuropsychiatry1, 100006 (2019).
  • Müller N . Inflammation in schizophrenia: pathogenetic aspects and therapeutic considerations. Schizophr. Bull.44(5), 973–982 (2018).
  • Mondelli V , DiForti M , MorganBP , MurrayRM , ParianteCM , DazzanP. Baseline high levels of complement component 4 predict worse clinical outcome at 1-year follow-up in first-episode psychosis. Brain Behav. Immun.88, 913–915 (2020).
  • Mondelli V , CiufoliniS , BelvederiMurri Met al. Cortisol and inflammatory biomarkers predict poor treatment response in first episode psychosis. Schizophr. Bull.41(5), 1162–1170 (2015).
  • Monroe JM , BuckleyPF , MillerBJ. Meta-analysis of anti-toxoplasma gondii IgM antibodies in acute psychosis. Schizophr. Bull.41(4), 989–998 (2015).
  • Anastasiadi D , Esteve-CodinaA , PiferrerF. Consistent inverse correlation between DNA methylation of the first intron and gene expression across tissues and species. Epigenetics Chromatin11(1), 37 (2018).
  • Lim YC , LiJ , NiYet al. A complex association between DNA methylation and gene expression in human placenta at first and third trimesters. PLOS ONE12(7), e0181155 (2017).
  • Hannon E , DempsterE , VianaJet al. An integrated genetic-epigenetic analysis of schizophrenia: evidence for co-localization of genetic associations and differential DNA methylation. Genome Biol.17(1), 176 (2016).
  • Hannon E , SpiersH , VianaJet al. Methylation quantitative trait loci in the developing brain and their enrichment in schizophrenia-associated genomic regions. Nat. Neurosci.19(1), 48–54 (2016).
  • Need AC , KeefeRS , GeDet al. Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis. Eur. J. Hum. Genet.17(7), 946–957 (2009).
  • Le Clerc S , TaingL , FondGet al. A double amino-acid change in the HLA-A peptide-binding groove is associated with response to psychotropic treatment in patients with schizophre-nia. Transl. Psychiatry5(7), e608–e608 (2015).
  • Puangpetch A , VanwongN , NuntamoolN , HongkaewY , ChamnanphonM , SukasemC. CYP2D6 polymorphisms and their influence on risperidone treatment. Pharmacogenomics Pers. Med.9, 131–147 (2016).
  • Pinheiro DS , SantosR da S , de BritoRB , CruzAH da S , GhediniPC , ReisAAS. GSTM1/GSTT1 double-null genotype increases risk of treatment-resistant schizophrenia: a genetic association study in Brazilian patients. PLOS ONE12(8), e0183812 (2017).
  • Weng S , WangB , LiMet al. Genome-wide association study of antipsychotic-induced sinus bradycardia in Chinese schizophrenia patients. PLOS ONE16(4), e0249997 (2021).
  • Tang H , DaltonCF , SrisawatU , ZhangZJ , ReynoldsGP. Methylation at a transcription factor-binding site on the 5-HT1A receptor gene correlates with negative symptom treatment response in first episode schizophrenia. Int. J. Neuropsychopharmacol.17(4), 645–649 (2014).
  • Miura I , BundoM , HinoMet al. PM516. association of DNA methylation of Taq1A in the DRD2 with response to aripiprazole in acute schizophrenia. Int. J. Neuropsychopharmacol.19(Suppl. 1), 87 (2016).
  • Melka MG , CastellaniCA , RajakumarN , O’ReillyR , SinghSM. Olanzapine-induced methylation alters cadherin gene families and associated pathways implicated in psychosis. BMC Neurosci.15(1), 112 (2014).
  • Emsley RA , RobertsMC , RataemaneSet al. Ethnicity and treatment response in schizophrenia: a comparison of 3 ethnic groups. J. Clin. Psychiatry63(1), 6709 (2002).
  • Dong E , GraysonDR , GuidottiA , CostaE. Antipsychotic subtypes can be characterized by differences in their ability to modify GABAergic promoter methylation. Epigenomics1(1), 201–211 (2009).
  • Andrade A , BrenneckeA , MallatSet al. Genetic associations between voltage-gated calcium channels and psychiatric disorders. Int. J. Mol. Sci.20(14), 3537 (2019).
  • Boulenouar H , BenhatchiH , GuermoudiF , OumiloudAH , RahouiA. An actualized screening of schizophrenia-associated genes. Egypt. J. Med. Hum. Genet.23(1), 81 (2022).
  • Fu Y , ZhouN , BaiWet al. Association of the CACNA2D2 gene with schizophrenia in Chinese Han population. Peer J.8, e8521 (2020).
  • Mitra S , WernerC , DMD. Neuroadaptations and TGF-β signaling: emerging role in models of neuropsychiatric disorders. Mol. Psychiatry27(1), 296–306 (2022).
  • Wang K-S , LiuY , XuC , LiuX , LuoX. Family-based association analysis of NAV2 gene with the risk and age at onset of Alzheimer’s disease. J. Neuroimmunol.310, 60–65 (2017).
  • Yan J , KimS , NhoKet al. Hippocampal transcriptome-guided genetic analysis of correlated episodic memory phenotypes in Alzheimer’s disease. Front. Genet.6, 117 (2015).
  • Park H , YangJ , KimRet al. Mice lacking the PSD-95-interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation and impaired contextual fear conditioning. Sci. Rep.5(1), 16410 (2015).
  • Pappas AL , BeyAL , WangXet al. Deficiency of Shank2 causes manialike behavior that responds to mood stabilizers. JCI Insight2(20), e92052 (2017).
  • Berkel S , MarshallCR , WeissBet al. Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation. Nat. Genet.42(6), 489–491 (2010).
  • Cefalù AB , NotoD , ArpiMLet al. Novel LMF1 nonsense mutation in a patient with severe hypertriglyceridemia. J. Clin. Endocrinol. Metab.94(11), 4584–4590 (2009).
  • Yoshimura R , KakiharaS , SoyaA , UedaN , ShinkaiK , NakamuraJ. Effect of clonazepam treatment on antipsychotic drug-induced Meige syndrome and changes in plasma levels of GABA, HVA, and MHPG during treatment. Psychiatry Clin. Neurosci.55(5), 543–546 (2001).
  • Jones PA , JonesPA. The DNA methylation paradox. Trends Genet.15(1), 34–37 (1999).

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