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Review

The impact of genetics on future drug discovery in schizophrenia

, , , , &
Pages 673-686 | Received 24 Jan 2017, Accepted 25 Apr 2017, Published online: 18 May 2017

References

  • Dunlop J, Brandon NJ. Schizophrenia drug discovery and development in an evolving era: are new drug targets fulfilling expectations?. J Psychopharmacol. 2015;29:230–238.
  • Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet. 2016;388:86–97.
  • Moran P, Stokes J, Marr J, et al. Gene x environment interactions in schizophrenia: evidence from genetic mouse models. Neural Plast. 2016;2016:2173748.
  • Beck K, Javitt DC, Howes OD. Targeting glutamate to treat schizophrenia: lessons from recent clinical studies. Psychopharmacology (Berl). 2016;233:2425–2428.
  • Bugarski-Kirola D, Iwata N, Samelijak S, et al. Efficacy and safety of adjunctive bitopertin versus placebo in patients with suboptimally controlled symptoms of schizophrenia treated with antipsychotics: results from three phase 3, randomised, double-blind, parallel-group, placebo-controlled, multicentre studies in the SearchLyte clinical trial program. Lancet Psychiatry. 2016;3:1115–1128.
  • Burgarski-Kirola D, Wang A, Abi-Saab D, et al. A phase II/III trial of bitopertin in monotherapy compared with placebo in patients with an acute exacerbation of schizophrenia – results from the CandleLyte study. Eur Neuropsychopharmacol. 2014;24:1024–1036.
  • Umbricht D, Alberati D, Martin-Facklam M, et al. Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: a randomized, double-blind, proof-of-concept study. JAMA Psychiatry. 2014;71:637–646.
  • Adams DH, Kinon BJ, Baygani S, et al. A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia. BMC Psychiatry. 2013;13:143.
  • Adams DH, Zhang L, Millen BA, et al. Pomaglumetad methionil (LY2140023) monohydrate) and aripiprazole in patients with schizophrenia: A phase 3, multicenter, double-blind comparison. Schizophr Res Treatment. 2014:758212.
  • Downing AM, Kinon BJ, Millen BA, Zhang L, Liu L, Morozova MA, et al. A double-blind, placebo-controlled comparator study of LY2140023 monohydrate in patients with schizophrenia. BMC Psychiatry. 2014;14:351.
  • Kinon BJ, Millen BA, Zhang L, et al. Exploratory analysis for a targeted population responsive to the metabotropic glutamate 2/3 receptor agonist pomaglumetad methionil in schizophrenia. Biol Psychiatry. 2015;78:754–762.
  • Kinon BJ, Zhang L, Millen BA, et al. A multicenter, inpatient, phase 2, double-blind, placebo-controlled dose-ranging study of LY2140023 monohydrate in patients with DSM-IV schizophrenia. J Clin Psychopharmacol. 2011;31:349–355.
  • Patil ST, Zhang L, Martenyi F, et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat Med. 2007;13:1103–1108.
  • Stauffer VL, Millen BA, Andersen S, et al. Pomaglumetad methionil: no significant difference as an adjunctive treatment for patients with prominent negative symptoms of schizophrenia compared to placebo. Schizophr Res. 2013;150:434–441.
  • Liu W, Downing AC, Munsie LM, Chen P, Reed MR, Ruble CL, et al. Pharmacogenetic analysis of the mGlu2/3 agonist LY2140023 monohydrate in the treatment of schizophrenia. Pharmacogenomics J. 2012;12:246–254.
  • Marek GJ. When is a proof-of-concept (POC) not a POC? Pomaglumetad (LY2140023) as a case study for antipsychotic efficacy. Curr Pharm Des. 2015;21:3788–3796.
  • Haig G, Wang D, Othman AA, et al. The a7 nicotinic agonist ABT-126 in the treatment of cognitive impairment associated with schizophrenia in non-smokers: Results from a randomized controlled phase 2b study. Neuropsychopharmacol. 2016;41:2893–2902.
  • Haig GM, Bain EE, Robieson WZ, et al. A randomized trial to assess the efficacy and safety of ABT-126, a selective a7 nicotinic receptor agonist, in the treatment of cognitive impairment in schizophrenia. Am J Psychiatry. 2016;173:827–835.
  • Keefe RS, Meltzer HA, Dgetluck N, et al. Randomized, double-blind, placebo-controlled study of encenicline, an α7 nicotinic acetylcholine receptor agonist, as a treatment for cognitive impairment in schizophrenia. Neuropsychopharmacol. 2015;40:3053–3060.
  • Umbricht D, Keefe RSE, Murray S, et al. A randomized, placebo-controlled study investigating the nicotinic a7 agonist, RG3487, for cognitive deficits in schizophrenia. Neuropsychopharmacol. 2014;39:1568–1577.
  • Corrigan MH, Gallen CC, Bonura L, et al., Group ftSS; Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: A placebo-controlled trial. Biol Psychiatry. 2004;55:445–451.
  • Kramer MS, Last B, Getson A, et al., Group tDDA; The effects of a selective D4 dopamine receptor antagonist (L-745,870) in acutely psychotic inpatients with schizophrenia. Arch Gen Psychiatry. 1997;54:567–572.
  • Redden L, Renenbach-Mueller B, Abi-Saab WM, et al. A double-blind, randomized, placebo-controlled study of the dopamine D3 receptor antagonist ABT-925 in patients with acute schizophrenia. J Clin Psychopharmacol. 2011;31:221–225.
  • Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomized, placebo-controlled phase 3 trial. Lancet. 2014;383:533–540.
  • Marder SR. Limitations of dopamine-D2 antagonists and the search for novel antipsychotic strategies. Neuropsychopharmacol. 1999;21(S6):S117–S21.
  • Meltzer HY, Arvanitis L, Bauer D, Rein W, Group M-TS. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorders. Am J Psychiatry. 2004;161:975–984.
  • Meltzer HY, Elkis H, Vanover K, et al. Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2 mg/day, but does not enhance efficacy of haloperidol, 2 mg/day: Comparison with reference dose risperidone, 6 mg/day. Schizophr Res. 2012;141:144–152.
  • Ebdrup BH, Rasmussen H, Arnt J, et al. Serotonin 2A receptor antagonists for treatment of schizophrenia. Expert Opin Investig Drugs. 2011;20:1211–1223.
  • Shen JH, Zhao Y, Rosenzweig-Lipson S, et al. A 6-week randomized, double-blind, placebo-controlled, comparator referenced trial of vabicaserin in acute schizophrenia. J Psychiatr Res. 2014;53:14–22.
  • Newcomer JW, Faustman WO, Zipursky RB, et al. Zacopride in schizophrenia: A single-blind serotonin type 3 antagonist trial. Arch Gen Psychiatry. 1992;49:751–752.
  • Morozova M, Lepilkina TA, Rupchev GE, et al. Add-on clinical effects of selective antagonist of 5-HT6 receptors AVN-211 (CD-008-0173) in patients with schizophrenia stabilized on antipsychotic treatment: pilot study. CNS Spectr. 2014;19:316–323.
  • Lundbeck H A randomized, double-blind, parallel-group, fixed dose study exploring the efficacy and safety of Lu AE58054 as augmentation therapy to risperidone in patients with schizophrenia. NCT00810667: ClinicalTrials.gov; 2010.
  • Litman RE, Smith M, Desai D, et al. The selective NK3 antagonist AZD2624 does not improve symptoms or cognition in schizophrenia. New Orleans (LA): Society of Biological Psychiatry; 2010.
  • Shekhar A, Potter WZ, Lightfoot J, et al. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry. 2008;165:1033–1039.
  • Haig GM, Bain EE, Robieson W, et al. A randomized trial of the efficacy and safety of the H3 antagonist ABT-288 in cognitive impairment associated with schizophrenia. Schizophrenia Bull. 2014;40:1433–1442.
  • Jarskog LF, Lowy MT, Grove RA, et al. A phase 2 study of a histamine H3 receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy. Schizophr Res. 2015;164:136–142.
  • Egan MF, Zhao X, Gottwald R, et al. Randomized crossover study of the histamine H3 inverse agonist MK-0249 for the treatment of cognitive impairment of schizophrenia. Schizophrenia Res. 2013;146:224–230.
  • Buchanan RW, Keefe RS, Lieberman J, et al. A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol Psychiatry. 2011;69:442–449.
  • Burmeister M, McInnis MG, Zollner S. Psychiatric genetics: progress amid controversy. Nat Rev Genet. 2008;9:527–540.
  • Le Couteur DG, Hunter S, Brayne C. Solanezumab and the amyloid hypothesis for Alzheimer’s disease. BMJ. 2016;355:i6771.
  • Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–427. Epub 2014/07/25.
  • Stefansson H, Rujescu D, Cichon S, et al. Large recurrent microdeletions associated with schizophrenia. Nature. 2008;455:232–236.
  • Walsh T, McClellan JM, McCarthy SE, et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science (New York, NY). 2008;320:539–543. Epub 2008/03/29.
  • Fromer M, Pocklington AJ, Kavanagh DH, et al. De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014;506:179–184.
  • Gulsuner S, Walsh T, Watts AC, et al.; Consortium on the Genetics of S, Group PS. Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell. 2013;154:518–529.
  • Purcell SM, Moran JL, Fromer M, et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature. 2014;506:185–190.
  • Genovese G, Fromer M, Stahl EA, et al. Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia. Nat Neurosci. 2016;19:1433–1441.
  • Shinawi M, Schaaf CP, Bhatt SS, et al. A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes. Nat Genet. 2009;41:1269–1271.
  • Harrison PJ. Recent genetic findings in schizophrenia and their therapeutic relevance. J Psychopharmacol. 2015;29:85–96.
  • BrainSeq AHBGC. BrainSeq: neurogenomics to drive novel target discovery for neuropsychiatric disorders. Neuron. 2015;88:1078–1083.
  • Brennand KJ, Simone A, Jou J, et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature. 2011;473:221–225.
  • Walton NM, Zhou Y, Kogan JH, et al. Detection of an immature dentate gyrus feature in human schizophrenia/bipolar patients. Transl Psychiatry. 2012;2:e135.
  • Hagihara H, Takao K, Walton NM, et al. Immature dentate gyrus: an endophenotype of neuropsychiatric disorders. Neural Plast. 2013;2013:1–24.
  • Shin R, Kobayashi K, Hagihara H, et al. The immature dentate gyrus represents a shared phenotype of mouse models of epilepsy and psychiatric disease. Bipolar Disord. 2013;15:405–421.
  • De Koning A, Walton NM, Shin R, et al. Derivation of neural stem cells from an animal model of psychiatric disease. Transl Psychiatry. 2013;3:e323.
  • Walton NM, De Koning A, Xie X, et al. Gastrin-releasing peptide contributes to the regulation of adult hippocampal neurogenesis and neuronal development. Stem Cells. 2014;32:2454–2466.
  • Orban PC, Chui D, Marth JD. Tissue- and site-specific DNA recombination in transgenic mice. Proc Natl Acad Sci U S A. 1992;89:6861–6865.
  • Tsien JZ, Chen DF, Gerber D, et al. Subregion- and cell type-restricted gene knockout in mouse brain. Cell. 1996;87:1317–1326.
  • Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A. 1992;89:5547–5551.
  • Jaisser F. Inducible gene expression and gene modification in transgenic mice. Jasn. 2000;11(Suppl 16):S95–S100.
  • Jinek M, Chylinski K, Fonfara I, et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science (New York, NY). 2012;337:816–821.
  • Sunagawa GA, Sumiyama K, Ukai-Tadenuma M, et al. Mammalian reverse genetics without crossing reveals Nr3a as a short-sleeper gene. Cell Rep. 2016;14:662–677.
  • Brandon NJ, Sawa A. Linking neurodevelopmental and synaptic theories of mental illness through DISC1. Nat Rev Neurosci. 2011;12:707–722.
  • Lindsay EA, Botta A, Jurecic V, et al. Congenital heart disease in mice deficient for the DiGeorge syndrome region. Nature. 1999;401:379–383.
  • Kimber WL, Hsieh P, Hirotsune S, et al. Deletion of 150 kb in the minimal DiGeorge/velocardiofacial syndrome critical region in mouse. Hum Mol Genet. 1999;8:2229–2237.
  • Karayiorgou M, Simon TJ, Gogos JA. 22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia. Nat Rev Neurosci. 2010;11:402–416.
  • Paylor R, McIlwain KL, McAninch R, et al. Mice deleted for the DiGeorge/velocardiofacial syndrome region show abnormal sensorimotor gating and learning and memory impairments. Hum Mol Genet. 2001;10:2645–2650.
  • Paylor R, Glaser B, Mupo A, et al. Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proc Natl Acad Sci U S A. 2006;103:7729–7734.
  • Hiroi N, Takahashi T, Hishimoto A, et al. Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders. Mol Psychiatry. 2013;18:1153–1165.
  • Meechan DW, Maynard TM, Tucker ES, et al. Modeling a model: mouse genetics, 22q11.2 deletion syndrome, and disorders of cortical circuit development. Prog Neurobiol. 2015;130:1–28.
  • Kirov G. CNVs in neuropsychiatric disorders. Hum Mol Genet. 2015;24:R45–9.
  • Kogan JH, Gross AK, Featherstone RE, et al. Mouse model of chromosome 15q13.3 microdeletion syndrome demonstrates features related to autism spectrum disorder. J Neurosci. 2015;35:16282–16294.
  • Lipska BK, Deep-Soboslay A, Weickert CS, et al. Critical factors in gene expression in postmortem human brain: focus on studies in schizophrenia. Biol Psychiatry. 2006;60:650–658.
  • Clementz BA, Sweeney JA, Hamm JP, et al. Identification of distinct psychosis biotypes using brain-based biomarkers. Am J Psychiatry. 2016;173:373–384.
  • Demjaha A, Murray RM, McGuire PK, et al. Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. Am J Psychiatry. 2012;169:1203–1210.
  • Lai CY, Scarr E, Udawela M, et al. Biomarkers in schizophrenia: a focus on blood based diagnostics and theranostics. World J Psychiatry. 2016;6:102–117.
  • Maccarrone G, Ditzen C, Yassouridis A, et al. Psychiatric patient stratification using biosignatures based on cerebrospinal fluid protein expression clusters. J Psychiatr Res. 2013;47:1572–1580.
  • Zhang T, Koutsouleris N, Meisenzahl E, et al. Heterogeneity of structural brain changes in subtypes of schizophrenia revealed using magnetic resonance imaging pattern analysis. Schizophr Bull. 2015;41:74–84.
  • Wheeler AL, Wessa M, Szeszko PR, et al. Further neuroimaging evidence for the deficit subtype of schizophrenia: a cortical connectomics analysis. JAMA Psychiatry. 2015;72:446–455.
  • Dickinson D, Pratt DN, Giangrande EJ, et al. Attacking heterogeneity in schizophrenia by deriving clinical subgroups from widely available symptom data. Schizophr Bull. 2017.
  • Schwarz E, Tost H, Meyer-Lindenberg A. Working memory genetics in schizophrenia and related disorders: an RDoC perspective. Am J Med Genet B Neuropsychiatr Genet. 2016;171B:121–131.
  • Insel TR. The NIMH Research Domain Criteria (RDoC) project: precision medicine for psychiatry. Am J Psychiatry. 2014;171:395–397.
  • Arnedo J, Svrakic DM, Del Val C, et al. Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies. Am J Psychiatry. 2015;172:139–153.
  • McClellan J, King MC. Genetic heterogeneity in human disease. Cell. 2010;141:210–217.
  • Millan MJ, Andrieux A, Bartzokis G, et al. Altering the course of schizophrenia: progress and perspectives. Nat Rev Drug Discov. 2016;15:485–515.
  • Cannon TD, Cadenhead K, Cornblatt B, et al. Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. Arch Gen Psychiatry. 2008;65:28–37.
  • Seidman LJ, Shapiro DI, Stone WS, et al. Association of neurocognition with transition to psychosis: baseline functioning in the second phase of the North American prodrome longitudinal study. JAMA Psychiatry. 2016;73:1239–1248.
  • Addington J, Cadenhead KS, Cornblatt BA, et al. North American prodrome longitudinal study (NAPLS 2): overview and recruitment. Schizophr Res. 2012;142:77–82.
  • Stone WS, Mesholam-Gately RI, Giuliano AJ, et al. Healthy adolescent performance on the MATRICS Consensus Cognitive Battery (MCCB): developmental data from two samples of volunteers. Schizophr Res. 2016;172:106–113.
  • Kelleher I, Clarke MC, Rawdon C, et al. Neurocognition in the extended psychosis phenotype: performance of a community sample of adolescents with psychotic symptoms on the MATRICS neurocognitive battery. Schizophr Bull. 2013;39:1018–1026.
  • Schmidt A, Cappucciati M, Radua J, et al. Improving prognostic accuracy in subjects at clinical high risk for psychosis: systematic review of predictive models and meta-analytical sequential testing simulation. Schizophr Bull. 2017;43:375–388.
  • Hirano Y, Oribe N, Kanba S, et al. Spontaneous gamma activity in schizophrenia. JAMA Psychiatry. 2015;72:813–821. Epub 2015/01/15.
  • McNally JM, McCarley RW. Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities. Curr Opin Psychiatry. 2016;29:202–210. Epub 2016/02/24.
  • Singh S, Kumar A, Agarwal S, et al. Genetic insight of schizophrenia: past and future perspectives. Gene. 2014;535:97–100. Epub 2013/10/22.
  • Wray NR, Lee SH, Mehta D, et al. Research review: polygenic methods and their application to psychiatric traits. J Child Psychol Psychiatry. 2014;55:1068–1087. Epub 2014/08/19.
  • Pearlson GD, Clementz BA, Sweeney JA, et al. Does biology transcend the symptom-based boundaries of psychosis?. Psychiatr Clin North Am. 2016;39:165–174. Epub 2016/05/25.
  • Buxbaum JD, Bolshakova N, Brownfeld JM, et al. The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses. Mol Autism. 2014;5:34. Epub 2014/11/14.
  • Mj L, Liu Z, Wang P, et al. GWASdb v2: an update database for human genetic variants identified by genome-wide association studies. Nucleic Acids Res. 2016;44:D869–76. Epub 2015/11/29.
  • Toma C, Torrico B, Hervas A, et al. Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations. Mol Psychiatry. 2014;19:784–790. Epub 2013/09/04.
  • Lek M, Karczewski KJ, Minikel EV, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285–291. Epub 2016/08/19.
  • Nakamura T, Kazuno AA, Nakajima K, et al. Loss of function mutations in ATP2A2 and psychoses: A case report and literature survey. Psychiatry Clin Neurosci. 2016 Aug;70(8):342–350.
  • Smedemark-Margulies N, Brownstein CA, Vargas S, et al. A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia. Cold Spring Harb Mol Case Stud. 2016;2(5:a001008.
  • Zimbrean PC, Schilsky ML. Psychiatric aspects of Wilson disease: a review. Gen Hosp Psychiatry. 2014 Jan–Feb;36(1):53–62.
  • Sevin M, Lesca G, Baumann N, et al. The adult form of Niemann-Pick disease type C. Brain. 2007 Jan;130(Pt 1):120–133.
  • Bonnot O, Fraidakis MJ, Lucanto R, et al. Cerebrotendinous xanthomatosis presenting with severe externalized disorder: improvement after one year of treatment with chenodeoxycholic Acid. CNS Spectr. 2010 Apr;15(4):231–236.
  • Hayashi T, Nakamura M, Ichiba M, et al. Adult-type metachromatic leukodystrophy with compound heterozygous ARSA mutations: a case report and phenotypic comparison with a previously reported case. Psychiatry Clin Neurosci. 2011 Feb;65(1):105–108.
  • Baumann N, Masson M, Carreau V, et al. Adult forms of metachromatic leukodystrophy: clinical and biochemical approach. Dev Neurosci. 1991;13(4–5):211–215.
  • Kemp S, Pujol A, Waterham HR, et al. ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. Hum Mutat. 2001 Dec;18(6):499–515.
  • Watson A, Pribadi M, Chowdari K, et al. C9orf72 repeat expansions that cause frontotemporal dementia are detectable among patients with psychosis. Psychiatry Res. 2016 Jan 30;235:200–202.
  • Halpin C, Owen G, Gutierrez-Espeleta GA, et al. Audiologic features of Norrie disease. Ann Otol Rhinol Laryngol. 2005 Jul;114(7):533–538.
  • Ohlmann A, Tamm ER. Norrin: molecular and functional properties of an angiogenic and neuroprotective growth factor. Prog Retin Eye Res. 2012 May;31(3):243–257.
  • Magini P, Pippucci T, Tsai IC, et al. A mutation in PAK3 with a dual molecular effect deregulates the RAS/MAPK pathway and drives an X-linked syndromic phenotype. Hum Mol Genet. 2014 Jul 1;23(13):3607–3617.
  • Schwartz CE, Tarpey PS, Lubs HA, et al. The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J Med Genet. 2007 Jul;44(7):472–477.
  • Alfaiz AA, Micale L, Mandriani B, Augello B, Pellico MT, Chrast J, et al. TBC1D7 mutations are associated with intellectual disability, macrocrania, patellar dislocation, and celiac disease. Hum Mutat. 2014 Apr;35(4):447–451.
  • Nakashima A, Yoshino K, Miyamoto T, et al. Identification of TBC7 having TBC domain as a novel binding protein to TSC1-TSC2 complex. Biochem Biophys Res Commun. 2007 Sep 14;361(1):218–223.
  • Salin-Cantegrel A, Riviere JB, Dupre N, et al. Distal truncation of KCC3 in non-French Canadian HMSN/ACC families. Neurology. 2007 Sep 25;69(13):1350–1355.
  • Peprah E. Fragile X syndrome: the FMR1 CGG repeat distribution among world populations. Ann Hum Genet. 2012 Mar;76(2):178–191.
  • Santoro MR, Bray SM, Warren ST. Molecular mechanisms of fragile X syndrome: a twenty-year perspective. Annu Rev Pathol. 2012;7:219–245.
  • Swanberg SE, Nagarajan RP, Peddada S, Yasui DH, LaSalle JM. Reciprocal co-regulation of EGR2 and MECP2 is disrupted in Rett syndrome and autism. Hum Mol Genet. 2009 Feb 1;18(3):525–534.
  • Stewart LR, Hall AL, Kang SH, et al. High frequency of known copy number abnormalities and maternal duplication 15q11-q13 in patients with combined schizophrenia and epilepsy. BMC Med Genet. 2011 Nov 25;12:154.
  • Bassett AS, Chow EW, AbdelMalik P, et al. The schizophrenia phenotype in 22q11 deletion syndrome. Am J Psychiatry. 2003 Sep;160(9):1580–1586.
  • McDonald-McGinn DM, Sullivan KE, Marino B, et al. 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2015 Nov 19;1:15071.
  • Portnoi MF, Lebas F, Gruchy N, et al. 22q11.2 duplication syndrome: two new familial cases with some overlapping features with DiGeorge/velocardiofacial syndromes. Am J Med Genet A. 2005 Aug 15;137(1):47–51.
  • Hiroi N, Takahashi T, Hishimoto A, et al. Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders. Mol Psychiatry. 2013 Nov;18(11):1153–1165.
  • Holtzman DM, Carrillo MC, Hendrix JA, et al. Tau: from research to clinical development. Alzheimers Dement. 2016;12:1033–1039. Epub 2016/05/08.
  • Iqbal K, Liu F, Gong CX. Tau and neurodegenerative disease: the story so far. Nat Rev Neurol. 2016;12:15–27. Epub 2015/12/05.
  • Arendt T, Stieler JT, Holzer M. Tau and tauopathies. Brain Res Bull. 2016;126:238–292. Epub 2016/09/13.
  • Puzzo D, Gulisano W, Palmeri A, et al. Rodent models for Alzheimer’s disease drug discovery. Expert Opin Drug Discov. 2015;10:703–711. Epub 2015/05/01.
  • Takao K, Kobayashi K, Hagihara H, et al. Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia. Neuropsychopharmacology. 2013;38:1409–1425.
  • Ohira K, Kobayashi K, Toyama K, et al. Synaptosomal-associated protein 25 mutation induces immaturity of the dentate granule cells of adult mice. Mol Brain. 2013;6:12.
  • Leussis MP, Berry-Scott EM, Saito M, et al. The ANK3 bipolar disorder gene regulates psychiatric-related behaviors that are modulated by lithium and stress. Biol Psychiatry. 2013;73:683–690.
  • Ruttimann E, Vacher CM, Gassmann M, et al. Altered hippocampal expression of calbindin-D-28k and calretinin in GABA(B(1))-deficient mice. Biochem Pharmacol. 2004;68:1613–1620.
  • Yamasaki N, Maekawa M, Kobayashi K, et al. Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders. Mol Brain. 2008;1:6.
  • Hattori S, Hagihara H, Ohira K, et al. In vivo evaluation of cellular activity in alphaCaMKII heterozygous knockout mice using manganese-enhanced magnetic resonance imaging (MEMRI). Front Integr Neurosci. 2013;7:76.
  • Grace AA. Dopamine system dysregulation by the hippocampus: implications for the pathophysiology and treatment of schizophrenia. Neuropharmacology. 2012;62:1342–1348.
  • Tamminga CA, Southcott S, Sacco C, et al. Glutamate dysfunction in hippocampus: relevance of dentate gyrus and CA3 signaling. Schizophr Bull. 2012;38:927–935.
  • Steinfeld H, Cho MT, Retterer K, et al. Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features. Neurogenetics. 2016;17:159–164.
  • Braida D, Guerini FR, Ponzoni L, et al. Association between SNAP-25 gene polymorphisms and cognition in autism: functional consequences and potential therapeutic strategies. Transl Psychiatry. 2015;5:e500.
  • Gerber DJ, Hall D, Miyakawa T, et al. Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit. Proc Natl Acad Sci U S A. 2003;100:8993–8998.

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