Advanced search
Publication Cover
Epigenomics Volume 5, 2013 - Issue 3
Submit an article Journal homepage
224
Views
3
CrossRef citations to date
0
Altmetric
Review

The Multidimensional Nature of Metabolic Syndrome in Schizophrenia: Lessons from Studies of One-Carbon Metabolism and DNA Methylation

Blazej MisiakCorrespondence[email protected]
View further author information
,
Dorota Frydecka1 Department of Psychiatry, Wroclaw Medical University, Pasteura 10, 51-367Wroclaw, PolandView further author information
,
Patryk Piotrowski1 Department of Psychiatry, Wroclaw Medical University, Pasteura 10, 51-367Wroclaw, PolandView further author information
&
Andrzej Kiejna1 Department of Psychiatry, Wroclaw Medical University, Pasteura 10, 51-367Wroclaw, PolandView further author information
Pages 317-329 | Published online: 11 Jun 2013

References

  • Saha S , ChantD, WelhamJ, McGrathJ. A systematic review of the prevalence of schizophrenia. PLoS Med.2(5) , e141 (2005).
  • Bushe CJ , TaylorM, HaukkaJ. Mortality in schizophrenia: a measurable clinical endpoint. J. Psychopharmacol.24(4 Suppl.) , 17–25 (2010).
  • Brown S . Excess mortality of schizophrenia. A meta-analysis. Br. J. Psychiatry171 , 502–508 (1997).
  • Auquier P , LanconC, RouillonF, LaderM. Mortality in schizophrenia. Pharmacoepidemiol. Drug Saf.16(12) , 1308–1312 (2007).
  • Correll CU . Balancing efficacy and safety in treatment with antipsychotics. CNS Spectr.12(10 Suppl. 17) , 12–20, 35 (2007).
  • Lieberman JA , StroupTS, McevoyJP et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 353(12) , 1209–1223 (2005).
  • Citrome L . Risk–benefit analysis of available treatments for schizophrenia. Psychiatric Times1 , 27–30 (2007).
  • Hasnain M , FredricksonSK, ViewegWV, PandurangiAK. Metabolic syndrome associated with schizophrenia and atypical antipsychotics. Curr. Diab. Rep.10(3) , 209–216 (2010).
  • Roerig JL , SteffenKJ, MitchellJE. Atypical antipsychotic-induced weight gain: insights into mechanisms of action. CNS drugs25(12) , 1035–1059 (2011).
  • Meguid MM , FetissovSO, VarmaM et al. Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition 16(10) , 843–857 (2000).
  • Wirshing DA , WirshingWC, KysarL et al. Novel antipsychotics: comparison of weight gain liabilities. J. Clin. Psychiatry 60(6) , 358–363 (1999).
  • Rege S . Antipsychotic induced weight gain in schizophrenia:mechanisms and management. Aust. N. Z. J. Psychiatry42(5) , 369–381 (2008).
  • Holt RI , PevelerRC. Obesity, serious mental illness and antipsychotic drugs. Diabetes Obes. Metab.11(7) , 665–679 (2009).
  • Kohen D . Diabetes mellitus and schizophrenia: historical perspective. Br. J. Psychiatry Suppl.47 , S64–S66 (2004).
  • Moteshafi H , ZhornitskyS, BrunelleS, StipE. Comparing tolerability of olanzapine in schizophrenia and affective disorders: a meta-analysis. Drugs Saf.35(10) , 819–836 (2012).
  • Dasgupta A , SinghOP, RoutJK, SahaT, MandalS. Insulin resistance and metabolic profile in antipsychotic naive schizophrenia patients. Prog. Neuropsychopharmacol. Biol. Psychiatry34(7) , 1202–1207 (2010).
  • Verma SK , SubramaniamM, LiewA, PoonLY. Metabolic risk factors in drug-naive patients with first-episode psychosis. J. Clin. Psychiatry70(7) , 997–1000 (2009).
  • Ryan MC , FlanaganS, KinsellaU, KeelingF, ThakoreJH. The effects of atypical antipsychotics on visceral fat distribution in first episode, drug-naive patients with schizophrenia. Life Sci.74(16) , 1999–2008 (2004).
  • Thakore JH , MannJN, VlahosI, MartinA, ReznekR. Increased visceral fat distribution in drug-naive and drug-free patients with schizophrenia. Int. J. Obes. Relat. Metab. Disord.26(1) , 137–141 (2002).
  • Ryan MC , SharifiN, CondrenR, ThakoreJH. Evidence of basal pituitary-adrenal overactivity in first episode, drug naive patients with schizophrenia. Psychoneuroendocrinology29(8) , 1065–1070 (2004).
  • Baptista T , SerranoA, UzcateguiE et al. The metabolic syndrome and its constituting variables in atypical antipsychotic-treated subjects: comparison with other drug treatments, drug-free psychiatric patients, first-degree relatives and the general population in Venezuela. Schizophr. Res. 126(1–3) , 93–102 (2011).
  • Martins JM , TrincaA, AfonsoA et al. Psychoneuroendocrine characteristics of common obesity clinical subtypes. Int. J. Obes. Relat. Metab. Disord. 25(1) , 24–32 (2001).
  • Mukherjee S , SchnurDB, ReddyR. Family history of Type 2 diabetes in schizophrenic patients. Lancet1(8636) , 495 (1989).
  • Vancampfort D , KnapenJ, ProbstM et al. Considering a frame of reference for physical activity research related to the cardiometabolic risk profile in schizophrenia. Psychiatry Res. 177(3) , 271–279 (2010).
  • Nasrallah HA . Linkage of cognitive impairments with metabolic disorders in schizophrenia. Am. J. Psychiatry167(10) , 1155–1157 (2010).
  • Lindenmayer JP , KhanA, KaushikS et al. Relationship between metabolic syndrome and cognition in patients with schizophrenia. Schizophr. Res. 142(1–3) , 171–176 (2012).
  • Krebs MO , BellonA, MainguyG, JayTM, FrielingH. One-carbon metabolism and schizophrenia: current challenges and future directions. Trends Mol. Med.15(12) , 562–570 (2009).
  • van Winkel R , MoonsT, PeerboomsO et al. MTHFR genotype and differential evolution of metabolic parameters after initiation of a second generation antipsychotic: an observational study. Int. Clin. Psychopharmacol.25(5) , 270–276 (2010).
  • van Winkel R , RuttenBP, PeerboomsO, PeuskensJ, van Os J, De Hert M. MTHFR and risk of metabolic syndrome in patients with schizophrenia. Schizophr. Res.121(1–3) , 193–198 (2010).
  • Ellingrod VL , MillerDD, TaylorSF, MolineJ, HolmanT, KerrJ. Metabolic syndrome and insulin resistance in schizophrenia patients receiving antipsychotics genotyped for the methylenetetrahydrofolate reductase ( MTHFR) 677C/T and 1298A/C variants. Schizophr. Res.98(1–3) , 47–54 (2008).
  • Ellingrod VL , TaylorSF, DalackG et al. Risk factors associated with metabolic syndrome in bipolar and schizophrenia subjects treated with antipsychotics: the role of folate pharmacogenetics. J. Clin. Psychopharmacol. 32(2) , 261–265 (2012).
  • Obeid R , HerrmannW. Homocysteine and lipids: S-adenosyl methionine as a key intermediate. FEBS Lett.583(8) , 1215–1225 (2009).
  • Brown AS , BottiglieriT, SchaeferCA et al. Elevated prenatal homocysteine levels as a risk factor for schizophrenia. Arch. Gen. Psychiatry 64(1) , 31–39 (2007).
  • Ganji V , KafaiMR. Population reference values for plasma total homocysteine concentrations in US adults after the fortification of cereals with folic acid. Am. J. Clin. Nutr.84(5) , 989–994 (2006).
  • Enquobahrie DA , FeldmanHA, HoelscherDH et al. Serum homocysteine and folate concentrations among a US cohort of adolescents before and after folic acid fortification. Public Health Nutr. 15(10) , 1818–1826 (2012).
  • Pfeiffer CM , OsterlohJD, Kennedy-StephensonJ et al. Trends in circulating concentrations of total homocysteine among US adolescents and adults: findings from the 1991–1994 and 1999–2004 National Health and Nutrition Examination Surveys. Clin. Chem. 54(5) , 801–813 (2008).
  • Greenlund KJ , SrinivasanSR, XuJH et al. Plasma homocysteine distribution and its association with parental history of coronary artery disease in black and white children: the Bogalusa Heart Study. Circulation 99(16) , 2144–2149 (1999).
  • Quinlivan EP , McpartlinJ, McnultyH et al. Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet 359(9302) , 227–228 (2002).
  • Liaugaudas G , JacquesPF, SelhubJ, RosenbergIH, BostomAG. Renal insufficiency, vitamin B(12) status, and population attributable risk for mild hyperhomocysteinemia among coronary artery disease patients in the era of folic acid-fortified cereal grain flour. Arterioscler. Thromb. Vasc. Biol.21(5) , 849–851 (2001).
  • Muntjewerff JW , KahnRS, BlomHJ, den Heijer M. Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis. Mol. Psychiatry11(2) , 143–149 (2006).
  • Neeman G , BlanaruM, BlochB et al. Relation of plasma glycine, serine, and homocysteine levels to schizophrenia symptoms and medication type. Am. J. Psychiatry 162(9) , 1738–1740 (2005).
  • Lipton SA , KimWK, ChoiYB et al. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc. Natl Acad. Sci. USA 94(11) , 5923–5928 (1997).
  • Bouaziz N , AyediI, SidhomO et al. Plasma homocysteine in schizophrenia: determinants and clinical correlations in Tunisian patients free from antipsychotics. Psychiatry Res. 179(1) , 24–29 (2010).
  • Roffman JL , BrohawnDG, NitensonAZ, MacklinEA, SmollerJW, GoffDC. Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia. Schizophr Bull.39(2) , 330–338 (2013).
  • Ayesa-Arriola R , Perez-IglesiasR, Rodriguez-SanchezJM et al. Homocysteine and cognition in first-episode psychosis patients. Eur. Arch. Psychiatry Clin. Neurosci. 262(7) , 557–564 (2012).
  • Bicikova M , HamplR, HillM, RipovaD, MohrP, PutzZ. Neuro- and immunomodulatory steroids and other biochemical markers in drug-naive schizophrenia patients and the effect of treatment with atypical antipsychotics. Neuro Endocrinol. Lett.32(2) , 141–147 (2011).
  • Kale A , NaphadeN, SapkaleS et al. Reduced folic acid, vitamin B12 and docosahexaenoic acid and increased homocysteine and cortisol in never-medicated schizophrenia patients: implications for altered one-carbon metabolism. Psychiatry Res. 175(1–2) , 47–53 (2010).
  • Frankenburg FR . The role of one-carbon metabolism in schizophrenia and depression. Harv. Rev. Psychiatry15(4) , 146–160 (2007).
  • Hashimoto K , EngbergG, ShimizuE, NordinC, LindstromLH, IyoM. Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients. Prog. Neuropsychopharmacol. Biol. Psychiatry29(5) , 767–769 (2005).
  • Bendikov I , NadriC, AmarS et al. A CSF and postmortem brain study of D-serine metabolic parameters in schizophrenia. Schizophr. Res. 90(1–3) , 41–51 (2007).
  • Sumiyoshi T , AnilAE, JinD, JayathilakeK, LeeM, MeltzerHY. Plasma glycine and serine levels in schizophrenia compared with normal controls and major depression: relation to negative symptoms. Int. J. Neuropsychopharmacol.7(1) , 1–8 (2004).
  • Ulrich CM , RobienK, SparksR. Pharmacogenetics and folate metabolism – a promising direction. Pharmacogenomics3(3) , 299–313 (2002).
  • Adkins DE , AbergK, McClayJL et al. Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs. Mol. Psychiatry 16(3) , 321–332 (2011).
  • Vasilopoulos Y , SarafidouT, BagiatisV et al. Association between polymorphisms in MTHFR and APOA5 and metabolic syndrome in the Greek population. Genet. Test. Mol. Biomarkers 15(9) , 613–617 (2011).
  • Chen AR , ZhangHG, WangZP et al. C-reactive protein, vitamin B12 and C677T polymorphism of N-5,10-methylenetetrahydrofolate reductase gene are related to insulin resistance and risk factors for metabolic syndrome in Chinese population. Clin. Invest. Med. 33(5) , E290–E297 (2010).
  • Russo GT , Di Benedetto A, Alessi E et al. Mild hyperhomocysteinemia and the common C677T polymorphism of methylene tetrahydrofolate reductase gene are not associated with the metabolic syndrome in Type 2 diabetes. J. Endocrinol. Invest.29(3) , 201–207 (2006).
  • Uehara SK , RosaG. Association of homocysteinemia with high concentrations of serum insulin and uric acid in Brazilian subjects with metabolic syndrome genotyped for C677T polymorphism in the methylenetetrahydrofolate reductase gene. Nutr. Res.28(11) , 760–766 (2008).
  • Bondy B . Genetics in psychiatry: are the promises met? World J. Biol. Psychiatry12(2) , 81–88 (2011).
  • Ma DK , MarchettoMC, GuoJU, MingGL, GageFH, SongH. Epigenetic choreographers of neurogenesis in the adult mammalian brain. Nat. Neurosci.13(11) , 1338–1344 (2010).
  • Sun J , MingGL, SongH. Epigenetic regulation of neurogenesis in the adult mammalian brain. Eur. J. Neurosci.33(6) , 1087–1093 (2011).
  • Parsons TE , SchmidtEJ, BoughnerJC, JamniczkyHA, MarcucioRS, HallgrimssonB. Epigenetic integration of the developing brain and face. Dev. Dyn.240(10) , 2233–2244 (2011).
  • Kohyama J , KojimaT, TakatsukaE et al. Epigenetic regulation of neural cell differentiation plasticity in the adult mammalian brain. Proc. Natl Acad. Sci. USA 105(46) , 18012–18017 (2008).
  • Lubin FD . Epigenetic gene regulation in the adult mammalian brain: multiple roles in memory formation. Neurobiol. Learn. Mem.96(1) , 68–78 (2011).
  • Puckett RE , LubinFD. Epigenetic mechanisms in experience-driven memory formation and behavior. Epigenomics3(5) , 649–664 (2011).
  • Belden WJ , LewisZA, SelkerEU, LorosJJ, DunlapJC. CHD1 remodels chromatin and influences transient DNA methylation at the clock gene frequency. PLoS Genet.7(7) , e1002166 (2011).
  • Lu SX , TobinEM. Chromatin remodeling and the circadian clock: Jumonji C-domain containing proteins. Plant Signal. Behav.6(6) , 810–814 (2011).
  • Hunter RG . Epigenetic effects of stress and corticosteroids in the brain. Front. Cell. Neurosci.6 , 18 (2012).
  • Graff J , ReiD, GuanJS et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 483(7388) , 222–226 (2012).
  • Karpinski P , SzmidaE, MisiakB et al. Assessment of three epigenotypes in colorectal cancer by combined bisulfite restriction analysis. Mol. Carcinog. 51(12) , 1003–1008 (2012).
  • Kozlowska J , KarpinskiP, SzmidaE et al. Assessment of chromosomal imbalances in CIMP-high and CIMP-low/CIMP-0 colorectal cancers. Tumour Biol. 33(4) , 1015–1019 (2012).
  • Dempster E , VianaJ, PidsleyR, MillJ. Epigenetic studies of schizophrenia: progress, predicaments, and promises for the future. Schizophr. Bull.39(1) , 11–16 (2013).
  • Iwamoto K , KatoT. Epigenetic profiling in schizophrenia and major mental disorders. Neuropsychobiology60(1) , 5–11 (2009).
  • Mill J , TangT, KaminskyZ et al. Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am. J. Hum. Genet. 82(3) , 696–711 (2008).
  • Gavin DP , SharmaRP. Histone modifications, DNA methylation, and schizophrenia. Neurosci. Biobehav. Rev.34(6) , 882–888 (2010).
  • Abdolmaleky HM , SmithCL, FaraoneSV et al. Methylomics in psychiatry: Modulation of gene-environment interactions may be through DNA methylation. Am. J. Med. Genet. B Neuropsychiatr. Genet. 127B(1) , 51–59 (2004).
  • Abdolmaleky HM , ChengKH, FaraoneSV et al. Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Hum. Mol. Genet. 15(21) , 3132–3145 (2006).
  • Murphy BC , O‘ReillyRL, SinghSM. Site-specific cytosine methylation in S-COMT promoter in 31 brain regions with implications for studies involving schizophrenia. Am. J. Med. Genet. B Neuropsychiatr. Genet.133B(1) , 37–42 (2005).
  • Abdolmaleky HM , ChengKH, RussoA et al. Hypermethylation of the reelin ( RELN) promoter in the brain of schizophrenic patients: a preliminary report. Am. J. Med. Genet. B Neuropsychiatr. Genet. 134B(1) , 60–66 (2005).
  • Lintas C , PersicoAM. Neocortical RELN promoter methylation increases significantly after puberty. Neuroreport21(2) , 114–118 (2010).
  • Grayson DR , JiaX, ChenY et al. Reelin promoter hypermethylation in schizophrenia. Proc. Natl Acad. Sci. USA 102(26) , 9341–9346 (2005).
  • Guidotti A , RuzickaW, GraysonDR et al. S-adenosyl methionine and DNA methyltransferase-1 mRNA overexpression in psychosis. Neuroreport 18(1) , 57–60 (2007).
  • Iwamoto K , BundoM, YamadaK et al. DNA methylation status of SOX10 correlates with its downregulation and oligodendrocyte dysfunction in schizophrenia. J. Neurosci. 25(22) , 5376–5381 (2005).
  • Abdolmaleky HM , YaqubiS, PapageorgisP et al. Epigenetic dysregulation of HTR2A in the brain of patients with schizophrenia and bipolar disorder. Schizophr. Res. 129(2–3) , 183–190 (2011).
  • Tolosa A , SanjuanJ, DagnallAM, MoltoMD, HerreroN, De Frutos R. FOXP2 gene and language impairment in schizophrenia: association and epigenetic studies. BMC Med. Genet.11 , 114 (2010).
  • Zhao C , WangF, PunFW et al. Epigenetic regulation on GABRB2 isoforms expression: developmental variations and disruptions in psychotic disorders. Schizophr. Res. 134(2–3) , 260–266 (2012).
  • Labonte B , TureckiG. The epigenetics of suicide: explaining the biological effects of early life environmental adversity. Arch. Suicide Res.14(4) , 291–310 (2010).
  • Ruzicka WB , ZhubiA, VeldicM, GraysonDR, CostaE, GuidottiA. Selective epigenetic alteration of layer I GABAergic neurons isolated from prefrontal cortex of schizophrenia patients using laser-assisted microdissection. Mol. Psychiatry12(4) , 385–397 (2007).
  • Veldic M , CarunchoHJ, LiuWS et al. DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains. Proc. Natl Acad. Sci. USA 101(1) , 348–353 (2004).
  • Rosa A , PicchioniMM, KalidindiS et al. Differential methylation of the X-chromosome is a possible source of discordance for bipolar disorder female monozygotic twins. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B(4) , 459–462 (2008).
  • Nohesara S , GhadirivasfiM, MostafaviS et al. DNA hypomethylation of MB-COMT promoter in the DNA derived from saliva in schizophrenia and bipolar disorder. J. Psychiatr. Res. 45(11) , 1432–1438 (2011).
  • Nishioka M , BundoM, KoikeS et al. Comprehensive DNA methylation analysis of peripheral blood cells derived from patients with first-episode schizophrenia. J. Hum. Genet. 58(2) , 91–97 (2013).
  • Pidsley R , MillJ. Epigenetic studies of psychosis: current findings, methodological approaches, and implications for postmortem research. Biol. Psychiatry69(2) , 146–156 (2010).
  • Carrard A , SalzmannA, MalafosseA, KaregeF. Increased DNA methylation status of the serotonin receptor 5HTR1A gene promoter in schizophrenia and bipolar disorder. J. Affect. Disord.132(3) , 450–453 (2010).
  • Ghadirivasfi M , NohesaraS, AhmadkhanihaHR et al. Hypomethylation of the serotonin receptor type-2A gene ( HTR2A) at T102C polymorphic site in DNA derived from the saliva of patients with schizophrenia and bipolar disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156B(5) , 536–545 (2011).
  • De Luca V , ViggianoE, DhootR, KennedyJL, WongAH. Methylation and QTDT analysis of the 5-HT2A receptor 102C allele: analysis of suicidality in major psychosis. J. Psychiatr. Res.43(5) , 532–537 (2009).
  • Melas PA , RogdakiM, OsbyU, SchallingM, LavebrattC, EkstromTJ. Epigenetic aberrations in leukocytes of patients with schizophrenia: association of global DNA methylation with antipsychotic drug treatment and disease onset. FASEB J.26(6) , 2712–2718 (2012).
  • Chen Y , ZhangJ, ZhangL, ShenY, XuQ. Effects of MAOA promoter methylation on susceptibility to paranoid schizophrenia. Hum. Genet.131(7) , 1081–1087 (2011).
  • McDonald PP , O‘ReillyR, SinghSM. Methylation analysis of the NOTCH4 – 25 C/T polymorphism in schizophrenia. Psychiatr. Genet.21(1) , 5–13 (2010).
  • Roffman JL , NitensonAZ, AgamY et al. A hypomethylating variant of MTHFR, 677C>T, blunts the neural response to errors in patients with schizophrenia and healthy individuals. PLoS ONE 6(9) , e25253 (2011).
  • Kordi-Tamandani DM , SahranavardR, TorkamanzehiA. DNA methylation and expression profiles of the brain-derived neurotrophic factor ( BDNF) and dopamine transporter ( DAT1) genes in patients with schizophrenia. Mol. Biol. Rep.39(12) , 10889–10893 (2012).
  • Kordi-Tamandani DM , DahmardehN, TorkamanzehiA. Evaluation of hypermethylation and expression pattern of GMR2, GMR5, GMR8, and GRIA3 in patients with schizophrenia. Gene515(1) , 163–166 (2012).
  • Petronis A , GottesmanII, KanP et al. Monozygotic twins exhibit numerous epigenetic differences: clues to twin discordance? Schizophr. Bull. 29(1) , 169–178 (2003).
  • Kuratomi G , IwamotoK, BundoM et al. Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins. Mol. Psychiatry 13(4) , 429–441 (2008).
  • Dempster EL , PidsleyR, SchalkwykLC et al. Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum. Mol. Genet. 20(24) , 4786–4796 (2011).
  • Bruce KD , CagampangFR. Epigenetic priming of the metabolic syndrome. Toxicol. Mech. Methods21(4) , 353–361 (2011).
  • Lillycrop KA , BurdgeGC. Epigenetic changes in early life and future risk of obesity. Int. J. Obes. (Lond.)35(1) , 72–83 (2011).
  • Kirkbride JB , SusserE, KundakovicM, KresovichJK, Davey Smith G, Relton CL. Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects? Epigenomics4(3) , 303–315 (2012).
  • Sicard MN , ZaiCC, TiwariAK et al. Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis. Pharmacogenomics 11(11) , 1561–1571 (2010).
  • Lott SA , BurghardtPR, BurghardtKJ, BlyMJ, GroveTB, EllingrodVL. The influence of metabolic syndrome, physical activity and genotype on catechol- O-methyl transferase promoter-region methylation in schizophrenia. Pharmacogenomics J. doi:10.1038/tpj.2012.6 (2012) (Epub ahead of print).
  • Burghardt KJ , PilsnerJR, BlyMJ, EllingrodVL. DNA methylation in schizophrenia subjects: gender and MTHFR 677C/T genotype differences. Epigenomics4(3) , 261–268 (2012).
  • Turcot V , TchernofA, DeshaiesY et al. LINE-1 methylation in visceral adipose tissue of severely obese individuals is associated with metabolic syndrome status and related phenotypes. Clin. Epigenetics 4(1) , 10 (2012).
  • Eren E , YeginA, YilmazN, HerkenH. Serum total homocystein, folate and vitamin B12 levels and their correlation with antipsychotic drug doses in adult male patients with chronic schizophrenia. Clin. Lab.56(11–12) , 513–518 (2010).
  • Sarandol A , KirliS, AkkayaC, OcakN, ErozE, SarandolE. Coronary artery disease risk factors in patients with schizophrenia: effects of short term antipsychotic treatment. J. Psychopharmacol.21(8) , 857–863 (2007).
  • Melas PA , RogdakiM, OsbyU, SchallingM, LavebrattC, EkstromTJ. Epigenetic aberrations in leukocytes of patients with schizophrenia: association of global DNA methylation with antipsychotic drug treatment and disease onset. FASEB J.26(6) , 2712–2718 (2012).
  • Dong E , NelsonM, GraysonDR, CostaE, GuidottiA. Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation. Proc. Natl Acad. Sci. USA105(36) , 13614–13619 (2008).
  • Dong E , ChenY, GavinDP, GraysonDR, GuidottiA. Valproate induces DNA demethylation in nuclear extracts from adult mouse brain. Epigenetics5(8) , 730–735 (2010).
  • Henderson DC , CopelandPM, NguyenDD et al. Homocysteine levels and glucose metabolism in non-obese, non-diabetic chronic schizophrenia. Acta Psychiatr. Scand. 113(2) , 121–125 (2006).
  • Akanji AO , OhaeriJU, Al-ShammriSA, FataniaHR. Associations of blood homocysteine concentrations in Arab schizophrenic patients. Clin. Biochem.40(13–14) , 1026–1031 (2007).
  • Vuksan-Cusa B , JakovljevicM, SagudM et al. Metabolic syndrome and serum homocysteine in patients with bipolar disorder and schizophrenia treated with second generation antipsychotics. Psychiatry Res. 189(1) , 21–25 (2011).
  • Vuksan-Cusa B , SagudM, JakovljevicM et al. Association between C-reactive protein and homocysteine with the subcomponents of metabolic syndrome in stable patients with bipolar disorder and schizophrenia. Nord. J. Psychiatry doi:10.3109/08039488.2012.745601 (2012) (Epub ahead of print).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.