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Accessing Gene Expression in Treatment-Resistant Schizophrenia

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Abstract

Schizophrenia (SCZ) is a mental disorder arising from a complex interaction of genetic and environmental factors. It has been suggested that treatment-resistant schizophrenia (TRS) is a distinct, more severe, and homogenous subgroup of schizophrenia that could present specific biological markers. Our aim was to characterize expression of target genes in blood of TRS patients compared with non-TRS (NTRS) patients and healthy controls (HC). TRS has been defined using failure to respond to two previous antipsychotic trials. We hypothesized that genes involved in neurodevelopment, myelination, neuroplasticity, neurotransmission, and miRNA processing could be involved in treatment resistance; then, we investigated 13 genes related to those processes in 256 subjects, being 94 healthy controls and 162 schizophrenia patients treated with antipsychotics. Of those, 78 were TRS patients and 84 were NTRS patients. Peripheral blood samples were collected from all subjects and RNA was isolated. Gene expression analysis was performed using the TaqMan low-density array (TLDA) technology. To verify the influence of expression quantitative trait loci (eQTLs), we evaluated single-nucleotide polymorphism (SNP) of all genes using data from GTEx Project. SNP genotypes were obtained from HumanOmniExpress BeadChip. We did not detect gene expression differences between TRS and NTRS subjects, indicating candidate genes specific to treatment resistance. We detected an upregulation of CNR1 and UFD1L gene expression in patients (TRS and NTRS groups) when compared to controls, that may be associated with the release of neurotransmitters, which can influence neuronal plasticity, or with a stress response-activating protein degradation. DICER1 and AKT1 expression increased slightly across the groups and could differentiate only the extreme opposite groups, HC and TRS. Both genes act in heterogeneous pathways, such as cell signaling and miRNA processing, and seem to have an increased demand in the TRS group. We did not detect any eQTLs in our sample that could explain differences in mRNA levels, suggesting a possible regulation by other mechanism, not driven by genotypes. Our data strengthen the importance of several biological pathways involved in the schizophrenia refractoriness and severity, adding knowledge to develop more effective treatments in the future.

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References

  1. Owen MJ, O'Donovan MC, Thapar A, Craddock N (2011) Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry 198(3):173–175. https://doi.org/10.1192/bjp.bp.110.084384

    Article  PubMed  PubMed Central  Google Scholar 

  2. Henriksen MG, Nordgaard J, Jansson LB (2017) Genetics of schizophrenia: overview of methods, findings and limitations. Front Hum Neurosci 11:322. https://doi.org/10.3389/fnhum.2017.00322

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gejman PV, Sanders AR, Kendler KS (2011) Genetics of schizophrenia: new findings and challenges. Annu Rev Genomics Hum Genet 12(1):121–144. https://doi.org/10.1146/annurev-genom-082410-101459

    Article  PubMed  CAS  Google Scholar 

  4. Boyle EA, Li YI, Pritchard JK (2017) An expanded view of complex traits: from polygenic to omnigenic. Cell 169(7):1177–1186. https://doi.org/10.1016/j.cell.2017.05.038

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Leucht S, Pitschel-Walz G, Abraham D, Kissling W (1999) Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr Res 35(1):51–68. https://doi.org/10.1016/S0920-9964(98)00105-4

    Article  PubMed  CAS  Google Scholar 

  6. Kapur S, Seeman P (2001) Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: a new hypothesis. Am J Psychiatry 158(3):360–369. https://doi.org/10.1176/appi.ajp.158.3.360

    Article  PubMed  CAS  Google Scholar 

  7. Kane JM, Honigfeld G, Singer J, Meltzer H (1988) Clozapine in treatment-resistant schizophrenics. Psychopharmacol Bull 24(1):62–67

    PubMed  CAS  Google Scholar 

  8. Taylor DM, Duncan-McConnell D (2000) Refractory schizophrenia and atypical antipsychotics. J Psychopharmacol 14(4):409–418. https://doi.org/10.1177/026988110001400411

    Article  PubMed  CAS  Google Scholar 

  9. McGorry P, Killackey E, Elkins K, Lambert M, Lambert T (2003) Summary Australian and New Zealand clinical practice guideline for the treatment of schizophrenia. Australasian Psychiatry 2(11):136–147

    Article  Google Scholar 

  10. Crespo-Facorro B, de la Foz VO, Ayesa-Arriola R, Perez-Iglesias R, Mata I, Suarez-Pinilla P et al (2013) Prediction of acute clinical response following a first episode of non affective psychosis: results of a cohort of 375 patients from the Spanish PAFIP study. Prog Neuro-Psychopharmacol Biol Psychiatry 44:162–167. https://doi.org/10.1016/j.pnpbp.2013.02.009

    Article  Google Scholar 

  11. Huber CG, Naber D, Lambert M (2008) Incomplete remission and treatment resistance in first-episode psychosis: definition, prevalence and predictors. Expert Opin Pharmacother 9(12):2027–2038. https://doi.org/10.1517/14656566.9.12.2027

    Article  PubMed  Google Scholar 

  12. Meltzer HY (1999) The role of serotonin in antipsychotic drug action. Neuropsychopharmacology 21(2 Suppl):106S–115S. https://doi.org/10.1016/S0893-133X(99)00046-9

    Article  PubMed  CAS  Google Scholar 

  13. Meltzer HY (1990) Defining treatment refractoriness in schizophrenia. Schizophr Bull 16(4):563–565. https://doi.org/10.1093/schbul/16.4.563

    Article  PubMed  CAS  Google Scholar 

  14. IPAP. The International Psychopharmacology Algorithm Project. 2009 [cited 2017 21/12/2017]; Available from: http://www.ipap.org/schiz/index.php.

  15. Andreasen NC, Pressler M, Nopoulos P, Miller D, Ho BC (2010 Feb 1) Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs. Biol Psychiatry 67(3):255–262. https://doi.org/10.1016/j.biopsych.2009.08.040

    Article  PubMed  CAS  Google Scholar 

  16. Spindola LM, Pan PM, Moretti PN, Ota VK, Santoro ML, Cogo-Moreira H, Gadelha A, Salum G et al (2017) Gene expression in blood of children and adolescents: mediation between childhood maltreatment and major depressive disorder. J Psychiatr Res 92:24–30. https://doi.org/10.1016/j.jpsychires.2017.03.015

    Article  PubMed  Google Scholar 

  17. Hruz T, Laule O, Szabo G, Wessendorp F, Bleuler S, Oertle L et al (2008) Genevestigator v3: a reference expression database for the meta-analysis of transcriptomes. Adv Bioinforma 2008:420747

    Article  Google Scholar 

  18. Christofolini DM, Bellucco FT, Ota VK, Belangero SI, Cernach MC, Gadelha A et al (2011) Assessment of 22q11.2 copy number variations in a sample of Brazilian schizophrenia patients. Schizophr Res 132(1):99–100. https://doi.org/10.1016/j.schres.2011.07.007

    Article  PubMed  Google Scholar 

  19. Gillespie AL, Samanaite R, Mill J, Egerton A, MacCabe JH (2017) Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? A systematic review. BMC Psychiatry 17(1):12. https://doi.org/10.1186/s12888-016-1177-y

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Anderson VM, Goldstein ME, Kydd RR, Russell BR (2015) Extensive gray matter volume reduction in treatment-resistant schizophrenia. Int J Neuropsychopharmacol 18(7):pyv016

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Demjaha A, Egerton A, Murray RM, Kapur S, Howes OD, Stone JM, McGuire PK (2014) Antipsychotic treatment resistance in schizophrenia associated with elevated glutamate levels but normal dopamine function. Biol Psychiatry 75(5):e11–e13. https://doi.org/10.1016/j.biopsych.2013.06.011

    Article  PubMed  CAS  Google Scholar 

  22. Demjaha A, Murray RM, McGuire PK, Kapur S, Howes OD (2012) Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. Am J Psychiatry 169(11):1203–1210. https://doi.org/10.1176/appi.ajp.2012.12010144

    Article  PubMed  Google Scholar 

  23. Krebs MO, Sautel F, Bourdel MC, Sokoloff P, Schwartz JC, Olie JP et al (1998) Dopamine D3 receptor gene variants and substance abuse in schizophrenia. Mol Psychiatry 3(4):337–341. https://doi.org/10.1038/sj.mp.4000411

    Article  PubMed  CAS  Google Scholar 

  24. Gouvea ES, Santos AFF, Ota VK, Mrad V, Gadelha A, Bressan RA et al (2017) The role of the CNR1 gene in schizophrenia: a systematic review including unpublished data. Rev Bras Psiquiatr 39(2):160–171. https://doi.org/10.1590/1516-4446-2016-1969

    Article  PubMed  Google Scholar 

  25. D'Souza DC, Abi-Saab WM, Madonick S, Forselius-Bielen K, Doersch A, Braley G et al (2005) Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol Psychiatry 57(6):594–608. https://doi.org/10.1016/j.biopsych.2004.12.006

    Article  PubMed  CAS  Google Scholar 

  26. Dinu IR, Popa S, Bicu M, Mota E, Mota M (2009) The implication of CNR1 gene’s polymorphisms in the modulation of endocannabinoid system effects. Rom J Intern Med 47(1):9–18

    PubMed  CAS  Google Scholar 

  27. Okahisa Y, Kodama M, Takaki M, Inada T, Uchimura N, Yamada M, Iwata N, Iyo M et al (2011 Mar) Association study of two cannabinoid receptor genes, CNR1 and CNR2, with methamphetamine dependence. Curr Neuropharmacol 9(1):183–189. https://doi.org/10.2174/157015911795017191

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Ujike H, Takaki M, Nakata K, Tanaka Y, Takeda T, Kodama M, Fujiwara Y, Sakai A et al (2002) CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia. Mol Psychiatry 7(5):515–518. https://doi.org/10.1038/sj.mp.4001029

    Article  PubMed  CAS  Google Scholar 

  29. Chavarria-Siles I, Contreras-Rojas J, Hare E, Walss-Bass C, Quezada P, Dassori A et al (2008) Cannabinoid receptor 1 gene (CNR1) and susceptibility to a quantitative phenotype for hebephrenic schizophrenia. Am J Med Genet B Neuropsychiatr Genet 147(3):279–284. https://doi.org/10.1002/ajmg.b.30592

    Article  PubMed  CAS  Google Scholar 

  30. Martinez-Gras I, Hoenicka J, Ponce G, Rodriguez-Jimenez R, Jimenez-Arriero MA, Perez-Hernandez E et al (2006) (AAT)n repeat in the cannabinoid receptor gene, CNR1: association with schizophrenia in a Spanish population. Eur Arch Psychiatry Clin Neurosci 256(7):437–441. https://doi.org/10.1007/s00406-006-0665-3

    Article  PubMed  Google Scholar 

  31. Hamdani N, Tabeze JP, Ramoz N, Ades J, Hamon M, Sarfati Y, Boni C, Gorwood P (2008) The CNR1 gene as a pharmacogenetic factor for antipsychotics rather than a susceptibility gene for schizophrenia. Eur Neuropsychopharmacol 18(1):34–40. https://doi.org/10.1016/j.euroneuro.2007.05.005

    Article  PubMed  CAS  Google Scholar 

  32. Grissom NM, Herdt CT, Desilets J, Lidsky-Everson J, Reyes TM (2015) Dissociable deficits of executive function caused by gestational adversity are linked to specific transcriptional changes in the prefrontal cortex. Neuropsychopharmacology 40(6):1353–1363. https://doi.org/10.1038/npp.2014.313

    Article  PubMed  CAS  Google Scholar 

  33. Kuntsi J, Frazier-Wood AC, Banaschewski T, Gill M, Miranda A, Oades RD, Roeyers H, Rothenberger A et al (2013) Genetic analysis of reaction time variability: room for improvement? Psychol Med 43(6):1323–1333. https://doi.org/10.1017/S0033291712002061

    Article  PubMed  CAS  Google Scholar 

  34. Johnson KA, Robertson IH, Kelly SP, Silk TJ, Barry E, Daibhis A et al (2007) Dissociation in performance of children with ADHD and high-functioning autism on a task of sustained attention. Neuropsychologia 45(10):2234–2245. https://doi.org/10.1016/j.neuropsychologia.2007.02.019

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ben Shalom D, Ronel Z, Faran Y, Meiri G, Gabis L, Kerns KA (2017) A double dissociation between inattentive and impulsive traits, on tasks of visual processing and emotion regulation. J Atten Disord 21(7):543–553. https://doi.org/10.1177/1087054713510351

    Article  PubMed  Google Scholar 

  36. Marco EM, Echeverry-Alzate V, Lopez-Moreno JA, Gine E, Penasco S, Viveros MP (2014) Consequences of early life stress on the expression of endocannabinoid-related genes in the rat brain. Behav Pharmacol 25(5–6):547–556. https://doi.org/10.1097/FBP.0000000000000068

    Article  PubMed  CAS  Google Scholar 

  37. D'Addario C, Micale V, Di Bartolomeo M, Stark T, Pucci M, Sulcova A, Palazzo M, Babinska Z et al (2017) A preliminary study of endocannabinoid system regulation in psychosis: distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia. Schizophr Res 188:132–140. https://doi.org/10.1016/j.schres.2017.01.022

    Article  PubMed  Google Scholar 

  38. Wilson RI, Nicoll RA (2002) Endocannabinoid signaling in the brain. Science 296(5568):678–682. https://doi.org/10.1126/science.1063545

    Article  PubMed  CAS  Google Scholar 

  39. Bassett AS, Chow EW, Husted J, Weksberg R, Caluseriu O, Webb GD, Gatzoulis MA (2005) Clinical features of 78 adults with 22q11 deletion syndrome. Am J Med Genet A 138(4):307–313. https://doi.org/10.1002/ajmg.a.30984

    Article  PubMed  PubMed Central  Google Scholar 

  40. Ota VK, Belangero SI, Gadelha A, Bellucco FT, Christofolini DM, Mancini TI, Ribeiro-dos-Santos ÂK, Santos SE et al (2010) The UFD1L rs5992403 polymorphism is associated with age at onset of schizophrenia. J Psychiatr Res 44(15):1113–1115. https://doi.org/10.1016/j.jpsychires.2010.04.008

    Article  PubMed  Google Scholar 

  41. Novelli G, Mari A, Amati F, Colosimo A, Sangiuolo F, Bengala M, Conti E, Ratti A et al (1998) Structure and expression of the human ubiquitin fusion-degradation gene (UFD1L). Biochim Biophys Acta 1396(2):158–162. https://doi.org/10.1016/S0167-4781(97)00211-X

    Article  PubMed  CAS  Google Scholar 

  42. Chen M, Gutierrez GJ, Ronai ZA (2011) Ubiquitin-recognition protein Ufd1 couples the endoplasmic reticulum (ER) stress response to cell cycle control. Proc Natl Acad Sci U S A 108(22):9119–9124. https://doi.org/10.1073/pnas.1100028108

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ye Y, Meyer HH, Rapoport TA (2001) The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature. [Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.] 414(6864):652–656

    CAS  Google Scholar 

  44. De Luca A, Pasini A, Amati F, Botta A, Spalletta G, Alimenti S et al (2001) Association study of a promoter polymorphism of UFD1L gene with schizophrenia. Am J medical Genetics. [Multicenter Study Research Support, Non-U.S. Gov't] 105(6):529–533

    Google Scholar 

  45. Ota VK, Berberian AA, Gadelha A, Santoro ML, Ottoni GL, Matsuzaka CT, Mari JJ, Melaragno MI et al (2013 Aug 30) Polymorphisms in schizophrenia candidate gene UFD1L may contribute to cognitive deficits. Psychiatry Res 209(1):110–113. https://doi.org/10.1016/j.psychres.2013.03.035

    Article  PubMed  CAS  Google Scholar 

  46. Gouvea ES, Ota VK, Noto C, Santoro ML, Spindola LM, Moretti PN, Carvalho CM, Xavier G et al (2016 Oct 04) Gene expression alterations related to mania and psychosis in peripheral blood of patients with a first episode of psychosis. Transl Psychiatry 6(10):e908. https://doi.org/10.1038/tp.2016.159

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Santarelli DM, Beveridge NJ, Tooney PA, Cairns MJ (2011) Upregulation of dicer and microRNA expression in the dorsolateral prefrontal cortex Brodmann area 46 in schizophrenia. Biol Psychiatry 69(2):180–187. https://doi.org/10.1016/j.biopsych.2010.09.030

    Article  PubMed  CAS  Google Scholar 

  48. Beveridge NJ, Gardiner E, Carroll AP, Tooney PA, Cairns MJ (2010) Schizophrenia is associated with an increase in cortical microRNA biogenesis. Mol Psychiatry 15(12):1176–1189. https://doi.org/10.1038/mp.2009.84

    Article  PubMed  CAS  Google Scholar 

  49. Sanders AR, Goring HH, Duan J, Drigalenko EI, Moy W, Freda J et al (2013) Transcriptome study of differential expression in schizophrenia. Hum Mol Genet 22(24):5001–5014. https://doi.org/10.1093/hmg/ddt350

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Camkurt MA, Karababa F, Erdal ME, Bayazit H, Kandemir SB, Ay ME et al (2016) Investigation of dysregulation of several microRNAs in peripheral blood of schizophrenia patients. Clin Psychopharmacol Neurosci 14(3):256–260. https://doi.org/10.9758/cpn.2016.14.3.256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Alacam H, Akgun S, Akca H, Ozturk O, Kabukcu BB, Herken H (2016) miR-181b-5p, miR-195-5p and miR-301a-3p are related with treatment resistance in schizophrenia. Psychiatry Res 245:200–206. https://doi.org/10.1016/j.psychres.2016.08.037

    Article  PubMed  CAS  Google Scholar 

  52. Balu DT, Carlson GC, Talbot K, Kazi H, Hill-Smith TE, Easton RM, Birnbaum MJ, Lucki I (2012 Feb) Akt1 deficiency in schizophrenia and impairment of hippocampal plasticity and function. Hippocampus 22(2):230–240. https://doi.org/10.1002/hipo.20887

    Article  PubMed  CAS  Google Scholar 

  53. Woodgett JR (2005) Recent advances in the protein kinase B signaling pathway. Curr Opin Cell Biol 17(2):150–157. https://doi.org/10.1016/j.ceb.2005.02.010

    Article  PubMed  CAS  Google Scholar 

  54. Arguello PA, Gogos JA (2008) A signaling pathway AKTing up in schizophrenia. J Clin Invest 118(6):2018–2021. https://doi.org/10.1172/JCI35931

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Emamian ES (2012) AKT/GSK3 signaling pathway and schizophrenia. Front Mol Neurosci 5:33

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Aubry JM, Schwald M, Ballmann E, Karege F (2009) Early effects of mood stabilizers on the Akt/GSK-3beta signaling pathway and on cell survival and proliferation. Psychopharmacology 205(3):419–429. https://doi.org/10.1007/s00213-009-1551-2

    Article  PubMed  CAS  Google Scholar 

  57. Tan HY, Nicodemus KK, Chen Q, Li Z, Brooke JK, Honea R, Kolachana BS, Straub RE et al (2008) Genetic variation in AKT1 is linked to dopamine-associated prefrontal cortical structure and function in humans. J Clin Invest 118(6):2200–2208. https://doi.org/10.1172/JCI34725

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA (2004) Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet 36(2):131–137. https://doi.org/10.1038/ng1296

    Article  PubMed  CAS  Google Scholar 

  59. Karege F, Perroud N, Schurhoff F, Meary A, Marillier G, Burkhardt S et al (2010) Association of AKT1 gene variants and protein expression in both schizophrenia and bipolar disorder. Genes Brain Behav 9(5):503–511. https://doi.org/10.1111/j.1601-183X.2010.00578.x

    Article  PubMed  CAS  Google Scholar 

  60. van Beveren NJ, Buitendijk GH, Swagemakers S, Krab LC, Roder C, de Haan L et al (2012) Marked reduction of AKT1 expression and deregulation of AKT1-associated pathways in peripheral blood mononuclear cells of schizophrenia patients. PLoS One 7(2):e32618. https://doi.org/10.1371/journal.pone.0032618

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Casseb SM, Simith DB, Melo KF, Mendonca MH, Santos AC, Carvalho VL, Cruz ACR, Vasconcelos PFC (2016) Drosha, DGCR8, and Dicer mRNAs are down-regulated in human cells infected with dengue virus 4, and play a role in viral pathogenesis. Genet Mol Res 15(2). https://doi.org/10.4238/gmr.15027891

  62. Dambal S, Giangreco AA, Acosta AM, Fairchild A, Richards Z, Deaton R, Wagner D, Vieth R et al (2017) microRNAs and DICER1 are regulated by 1,25-dihydroxyvitamin D in prostate stroma. J Steroid Biochem Mol Biol 167:192–202. https://doi.org/10.1016/j.jsbmb.2017.01.004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Meltzer HY, Rabinowitz J, Lee MA, Cola PA, Ranjan R, Findling RL, Thompson PA (1997 Apr) Age at onset and gender of schizophrenic patients in relation to neuroleptic resistance. Am J Psychiatry 154(4):475–482. https://doi.org/10.1176/ajp.154.4.475

    Article  PubMed  CAS  Google Scholar 

  64. Lieberman JA, Safferman AZ, Pollack S, Szymanski S, Johns C, Howard A, Kronig M, Bookstein P et al (1994) Clinical effects of clozapine in chronic schizophrenia: response to treatment and predictors of outcome. Am J Psychiatry 151(12):1744–1752. https://doi.org/10.1176/ajp.151.12.1744

    Article  PubMed  CAS  Google Scholar 

  65. Quintero J, Barbudo del Cura E, Lopez-Ibor MI, Lopez-Ibor JJ (2011) The evolving concept of treatment-resistant schizophrenia. Actas Esp Psiquiatr 39(4):236–250

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Genetics and Morphology, Universidade de Brasília (UNB), Brasília, Brazil

    Patricia N. Moretti

  2. Psychiatry Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil

    Patricia N. Moretti, Vanessa K. Ota, Eduardo S. Gouvea, Mariana Pedrini, Marcos L. Santoro, Fernanda Talarico, Leticia M. Spindola, Carolina Muniz Carvalho, Cristiano Noto, Gabriela Xavier, Elisa Brietzke, Ary Gadelha, Rodrigo Bressan & Jair Mari

  3. Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil

    Vanessa K. Ota, Marcos L. Santoro, Fernanda Talarico, Leticia M. Spindola, Carolina Muniz Carvalho, Gabriela Xavier & Sintia Belangero

  4. Interdisciplinary Laboratory of Clinical Neurosciences (LiNC), Psychiatry Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil

    Vanessa K. Ota, Marcos L. Santoro, Fernanda Talarico, Leticia M. Spindola, Carolina Muniz Carvalho, Cristiano Noto, Gabriela Xavier, Ary Gadelha, Rodrigo Bressan, Jair Mari & Sintia Belangero

  5. Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, Brazil

    Eduardo S. Gouvea

  6. Research Group in Behavioral and Molecular Neuroscience of Bipolar Disorder, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil

    Mariana Pedrini & Elisa Brietzke

  7. Disciplina de Genética, UNIFESP, Rua Botucatu, 740, Ed. Leitao da Cunha, 1° andar, São Paulo, CEP 04023-900, Brazil

    Sintia Belangero

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  1. Patricia N. Moretti
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Correspondence to Sintia Belangero.

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The Research Ethics Committee of UNIFESP approved the study, and all the participants and family members provided written informed consent prior to enrolment in the study (CAAE 06191612.7.0000.5505).

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Moretti, P.N., Ota, V.K., Gouvea, E.S. et al. Accessing Gene Expression in Treatment-Resistant Schizophrenia. Mol Neurobiol 55, 7000–7008 (2018). https://doi.org/10.1007/s12035-018-0876-4

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