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Reelin, GABA, FMRP, and Autism

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The Molecular Basis of Autism

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

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Abstract

Autism is a heterogeneous neurodevelopmental disorder. The etiology of autism remains unknown although both genetic and environmental factors are likely to be involved. These factors disrupt the course of normal brain development from the cellular to the gross anatomical levels. The Reelin, gamma-aminobutyric acid (GABA), and fragile X mental retardation protein (FMRP)—metabotropic glutamate receptor 5 (mGluR5) signaling systems play important roles during the development of the nervous system. Disruption of these pathways is likely to lead to altered synaptic transmission and, ultimately, the cognitive and behavioral deficits associated with autism. This chapter describes each of these signaling systems and summarizes the current evidence that link them to autism. Therapies that target molecules in these signaling systems may provide new means of treating the core symptoms of autism.

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References

  • American Psychiatric Association (APA) (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing, Washington, DC

    Google Scholar 

  • Ammassari-Teule M, Sgobio C, Biamonte F, Marrone C, Mercuri NB, Keller F (2009) Reelin haploinsufficiency reduces the density of PV + neurons in circumscribed regions of the striatum and selectively alters striatal-based behaviors. Psychopharmacology (Berl.) 204:511–521

    CAS  PubMed  Google Scholar 

  • Ashley-Koch AE, Jaworski J, Ma de Q, Mei H, Ritchie MD, Skaar DA, Robert Delong G, Worley G, Abramson RK, Wright HH, Cuccaro ML, Gilbert JR, Martin ER, Pericak-Vance MA (2007) Investigation of potential gene–gene interactions between APOE and RELN contributing to autism risk. Psychatr Genet 17:221–226

    Google Scholar 

  • Assadi AH, Zhang G, Beffert U, McNeil RS, Renfro AL, Niu S, Quattrocchi CC, Antalffy BA, Sheldon M, Armstrong DD, Wynshaw-Boris A, Herz J, D’Arcangelo G, Clark GD (2003) Interaction of Reelin signaling and Lis1 in brain development. Nat Genet 35:270–276

    CAS  PubMed  Google Scholar 

  • Bailey DB, Mesibov GB, Hatton DD, Clark RD, Roberts JE, Mayhew L (1998) Autistic behavior in young boys with fragile x syndrome. J Autism Dev Disord 28:499–507

    PubMed  Google Scholar 

  • Bardoni B, Schenck A, Mandel J-L (2001) The fragile X mental retardation protein. Brain Res Bull 56:375–382

    CAS  PubMed  Google Scholar 

  • Barr AM, Fish KN, Markou A, Honer WG (2008) Heterozygous reeler mice exhibit alterations in sensorimotor gating but not presynaptic proteins. Eur J Neurosci 27:2568–2574

    PubMed  Google Scholar 

  • Bear MF (2005) Therapeutic implications of the mGluR theory of fragile X mental retardation. Genes Brain Behav 4:393–398

    CAS  PubMed  Google Scholar 

  • Bear MF, Huber KM, Warren ST (2004) The mGluR theory of Fragile X mental retardation. Trends Neurosci 27:370–377

    CAS  PubMed  Google Scholar 

  • Beffert U, Morfini G, Bock HH, Reyna H, Brady ST, Herz J (2002) Reelin-mediated signalling locally regulates protein kinase B/Akt and glycogen synthase kinase 3β. J Biol Chem 51:49958–49964

    Google Scholar 

  • Beffert U, Weeber EJ, Durudas A, Qiu S, Masiulis I, Sweatt JD, Li WP, Adelmann G, Frotscher M, Hammer RE, Herz J (2005). Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron 47:567–579

    CAS  PubMed  Google Scholar 

  • Beffert U, Nematollah Farsian F, Masiulis I, Hammer RE, Yoon SO, Giehl KM, Herz J (2006) ApoE receptor 2 controls neuronal survival in the adult brain. Curr Biol 16:2446-2452

    Google Scholar 

  • Berry-Kravis E, Knox A, Hervey C (2011) Targeted treatments for fragile X syndrome. J Neurodev Disord 3:193–210

    PubMed Central  PubMed  Google Scholar 

  • Binnie CD (1993) Significance and management of transitory cognitive impairment due to subclinical EEG discharges in children. Brain Dev 15:23–30

    CAS  PubMed  Google Scholar 

  • Blatt GJ, Fitzgerald CM, Guptill JT, Booker AB, Kemper TL, Bauman ML (2001) Density and distribution of hippocampal neurotransmitter receptors in autism: an autoradiographic study. J Autism Dev Disord 31:537–544

    CAS  PubMed  Google Scholar 

  • Bonora E, Beyer KS, Lamb JA, Parr JR, Klauck SM, Benner A, Paolucci M, Abbott A, Ragoussis I, Poustka A, Bailey AJ, Monaco AP (2003) International molecular genetic study of autism (IMGSAC). Analysis of reelin as a candidate gene for autism. Mol Psychiatry 10:885–892

    Google Scholar 

  • Bouché E, Romero-Ortega MI, Henkemeyer M, Catchpole T, Leemhuis J, Frotscher M, May P, Herz J, Bock HH (2013) Reelin induces EphB activation. Cell Res 23:473–490

    PubMed Central  PubMed  Google Scholar 

  • Bowery NG (2000) GABAB receptors structure and function. In: Martin DL, Olsen RW (eds) GABA in the nervous system: the view at fifty years. Lippincott, Williams and Wilkins, Philadelphia, pp 233–244

    Google Scholar 

  • Boyle MP, Bernard A, Thompson CL, Ng L, Boe A, Mortrud M, Hawrylycz MJ, Jones AR, Hevner RF, Lein ES (2011) Cell-type-specific consequences of Reelin deficiency in the mouse neocortex, hippocampus, and amygdala. J Comp Neurol 519:2061–2089

    CAS  PubMed  Google Scholar 

  • Brandon NJ, Smart TG, Moss SJ (2000) Regulation of GABAA receptors by protein phosphorylation. In: Martin DL, Olsen RW (eds) GABA in the nervous system: the view at fifty years. Lippincott, Williams and Wilkins, Philadelphia, pp 191–206

    Google Scholar 

  • Canitano R (2007) Epilepsy in autism spectrum disorders. Eur Child Adolesc Psychiatry 16:61–66

    PubMed  Google Scholar 

  • Centers for Disease Control and Prevention (CDC) (2014) Prevalence of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States. MMWR Surveill Summ 63:1–21

    Google Scholar 

  • Chakrabarti S, Fombonne E (2005) Pervasive development disorders in preschool children: confirmation of high prevalence. Am J Psychiatry 162:1133–1341

    Google Scholar 

  • Chen Y, Beffert U, Ertunc M, Tang TS, Kavalali ET, Bezprozvanny I, Herz J (2005) Reelin modulates NMDA receptor activity in cortical neurons. J Neurosci 25:8209–8216

    CAS  PubMed  Google Scholar 

  • Chonchaiya W, Au J, Schneider A, Hessl D, Harris SW, Laird M, Mu Y, Tassone F, Nguyen DV, Hagerman RJ (2012). Increased prevalence of seizures in boys who were probands with the FMR1 premutation and co-morbid autism spectrum disorder. Hum Genet 131:581–589

    PubMed Central  PubMed  Google Scholar 

  • Collins AL, Ma D, Whitehead PL, Martin ER, Wright HH, Abramson RK, Hussman JP, Haines JL, Cuccaro ML, Gilbert JR, Pericak-Vance MA (2006) Investigation of autism and GABA receptor subunit genes in multiple ethnic groups. Neurogenetics 7:167–174

    PubMed Central  CAS  PubMed  Google Scholar 

  • D’Arcangelo G, Miao GG, Soares HD, Morgan JI, Curran T (1995) A protein related to extracellular matrix proteins detected in the mouse mutant reeler. Nature 374:719–723

    PubMed  Google Scholar 

  • D’Arcangelo G, Homayouni R, Keshvara L, Rice DS, Sheldon M, Curran T (1999) Reelin is a ligand for lipoprotein receptors. Neuron 24:471–479

    PubMed  Google Scholar 

  • D’Hulst C, De Geest N, Reeve SP, Van Dam D, De Deyn PP, Hassan BA, Kooy RF (2006) Decreased expression of the GABAA receptor in fragile X syndrome. Brain Res 1121:238–245

    PubMed  Google Scholar 

  • Darnell JC, Klann E (2013) The translation of translational control by FMRP: therapeutic targets for FXS. Nat Neurosci 16:1530–1536

    PubMed Central  CAS  PubMed  Google Scholar 

  • Darnell JC, Van Driesche SJ, Zhang C, Hung KY, Mele A, Fraser CE, Stone EF, Chen C, Fak JJ, Chi SW, Licatalosi DD, Richter JD, Darnell RB (2011) FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146:247–261

    PubMed Central  CAS  PubMed  Google Scholar 

  • de Vrij FM Levenga J van der Linde HC Koekkoek SK De Zeeuw CI Nelson DL Oostra BA Willemsen R (2008) Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiol Dis 31:127–132

    PubMed Central  PubMed  Google Scholar 

  • DeBergeyck V, Naerhuyzen B, Goffinet AM, deRouvroit C (1998) A panel of monoclonal antibodies against Reelin, the extracellular matrix protein defective in reeler mutant mice. J Neurosci Meth 82:17–24

    CAS  Google Scholar 

  • Devlin B, Bennett P, Dawson G, Figlewicz DA, Grigorenko EL, McMahon W, Minshew N, Pauls D, Smith M, Spence MA, Rodier PM, Stodgell C, Schellenberg GD, CPEA Genetics Network (2004) Alleles of a Reelin CGG repeat do not convey liability to autism in a sample from the CPEA network. Am J Med Genet 126B:46–50

    PubMed  Google Scholar 

  • Dölen G, Bear MF (2008) Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome. J Physiol 586:1503-1508

    Google Scholar 

  • Dölen G, Osterweil E, Shankaranarayana Rao BS, Smith GB, Auerbach D, Chattarji S, Bear MF (2007) Correction of fragile X syndrome in mice. Neuron 56:955–962

    PubMed Central  PubMed  Google Scholar 

  • Dutta S, Guhathakurta S, Sinha S, Chatterjee A, Ahmed S, Ghosh S, Gangopadhyay PK, Singh M, Usha R (2007) Reelin gene polymorphisms in the Indian population: a possible paternal 5’UTR-CGG-repeat-allele effect on autism. Am J Med Genet B Neuropsychiatr Genet 144B:106–112

    CAS  PubMed  Google Scholar 

  • Dutta S, Sinha S, Ghosh S, Chatterjee A, Ahmed S, Usha R (2008) Genetic analysis of Reelin gene (RELN) SNPs: no association with autism spectrum disorder in the Indian population. Neurosci Lett 441:56–60

    CAS  PubMed  Google Scholar 

  • Eastwood SL, Harrison PJ (2003) Interstitial white matter neurons express less Reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis. Mol Psychiatry 8:821–831

    CAS  Google Scholar 

  • Eastwood SL, Harrison PJ (2006) Cellular basis for reduced cortical Reelin expression in schizophrenia. Am J Psychiatry 163:540–542

    PubMed  Google Scholar 

  • El Idrissi A Ding XH Scalia J Trenkner E Brown WT Dobkin C (2005) Decreased GABAA receptor expression in the seizure-prone fragile X mouse. Neurosci Lett 377:141–146

    CAS  PubMed  Google Scholar 

  • Farzin F, Perry H, Hessl D, Loesch D, Cohen J, Bacalman S, Gane L, Tassone F, Hagerman P, Hagerman R (2006) Autism spectrum disorders and attention-deficit/hyperactivity disorder in boys with the fragile X premutation. J Dev Behav Pediatr 27:S137–S144

    Google Scholar 

  • Fatemi SH, Folsom TD (2011) Dysregulation of fragile X mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of subjects with autism: a postmortem brain study. Mol Autism 2:6

    PubMed Central  PubMed  Google Scholar 

  • Fatemi SH, Folsom TD (2015) GABA receptor subunit distribution and FMRP-mGluR5 signaling abnormalities in the cerebellum of subjects with schizophrenia, mood disorders, and autism. Schiz Res, in press

    Google Scholar 

  • Fatemi SH, Earle JA, McMenomy T (2000) Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder, and major depression. Mol Psychiatry 5:654–663

    CAS  PubMed  Google Scholar 

  • Fatemi SH, Stary JM, Halt AR, Realmuto G (2001) Dysregulation of Reelin and Bcl-2 proteins in autistic cerebellum. J Autism Dev Disord 6:529–535

    Google Scholar 

  • Fatemi SH, Stary JM, Egan EA (2002) Reduced blood levels of Reelin as a vulnerability factor in pathophysiology of autistic disorder. Cell Mol Neurobiol 22:139–152

    CAS  PubMed  Google Scholar 

  • Fatemi SH, Snow AV, Stary JM, Araghi-Niknam M, Brooks AI, Pearce DA, Reutiman TJ, Lee S (2005a) Reelin signaling is impaired in autism. Biol Psychiatry 57:777–787

    CAS  PubMed  Google Scholar 

  • Fatemi SH, Stary JM, Earle JA, Araghi-Niknam M, Egan E (2005b) GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins in cerebellum. Schizophr Res 72:109–122

    PubMed  Google Scholar 

  • Fatemi SH, Reutiman TJ, Folsom TD, Thuras PD (2009a) GABA(A) Receptor downregulation in brains of subjects with autism. J Autism Dev Disord 39:223–230

    PubMed Central  PubMed  Google Scholar 

  • Fatemi SH, Folsom TD, Reutiman TJ, Thuras PD (2009b) Expression of GABA(B) receptors is altered in brains of Subjects with autism. Cerebellum 8:64–69

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fatemi SH, Reutiman TJ, Folsom TD, Rooney RJ, Patel DH, Thuras PD (2010a) mRNA and protein levels for GABA(A) alpha 4, alpha 5, beta 1, and GABA(B)R1 receptors are altered in brains from subjects with autism. J Autism Dev Disord 40:743–750

    PubMed Central  PubMed  Google Scholar 

  • Fatemi SH, Kneeland RE, Liesch SB, Folsom TD (2010b) Fragile X mental retardation protein levels are decreased in major psychiatric disorders. Schizophr Res 124:246–247

    PubMed Central  PubMed  Google Scholar 

  • Fatemi SH, Folsom TD, Thuras PD (2011a) Deficits in GABA(B) receptor system in schizophrenia and mood disorders: a postmortem study. Schizophr Res 128:37–43

    PubMed Central  PubMed  Google Scholar 

  • Fatemi SH, Folsom TD, Kneeland RE, Liesch SB (2011b) Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both Fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism. Anat Rec 294:1635–1645

    CAS  Google Scholar 

  • Fatemi SH, Folsom TD, Rooney RJ, Thuras PD (2013a) mRNA and protein expression for novel GABAA receptors θ and ρ2 are altered in schizophrenia and mood disorders; relevance to FMRP-mGluR5 signaling pathway. Transl Psychiatry 3:e271

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fatemi SH, Folsom TD, Rooney RJ, Thuras PD (2013b) Expression of GABAA α2-, β1- and ε-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder. Transl Psychiatry 3:e303

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fatemi SH, Folsom TD, Kneeland RE, Yousefi M, Liesch S, Thuras PD (2013c) Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex. Mol Autism 4:21

    PubMed Central  PubMed  Google Scholar 

  • Fatemi SH, Reutiman TJ, Folsom TD, Rustan OG, Rooney RJ, Thuras PD (2014) Downregulation of GABAA receptor protein subunits α6, β2, ε, γ2, and ρ2 in superior frontal cortex of subjects with autism. J Autism Dev Disord 44(8):1833–1845

    PubMed  Google Scholar 

  • Folsom TD, Fatemi SH (2013) The involvement of Reelin in neurodevelopmental disorders. Neuropharmacology 68:122–135

    PubMed Central  CAS  PubMed  Google Scholar 

  • Frotscher M (1998) Cajal-Retzius cells, Reelin, and the formation of layers. Curr Opin Neurobiol 8:570–575

    CAS  PubMed  Google Scholar 

  • Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, Verkerk AJ, Holden JJ, Fenwick RG Jr, Warren ST et al (1991) Variation in the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67:1047–1058

    CAS  PubMed  Google Scholar 

  • Gaetz W, Bloy L, Wang DJ, Port RG, Blaskey L, Levy SE, Roberts TP (2013) GABA estimation in the brains of children on the autism spectrum: measurement precision and regional cortical variation. Neuroimage 86:1–9

    Google Scholar 

  • Gantois I, Vandescompele J, Speleman F, Reyniers E, D’Hooge R, Severijnen LA, Willemsen R, Tassone F, Kooy RF (2006) Expression profiling suggests underexpression of the GABAA receptor subunit delta in the fragile X knockout mouse model. Neurobiol Dis 21:346–357

    CAS  PubMed  Google Scholar 

  • Garber KB, Visootsak J, Warren ST, Oostra BA, Nelson DL, Caskey CT (2008) Fragile X syndrome. Eur J Hum Genet 16:666–672

    PubMed Central  CAS  PubMed  Google Scholar 

  • Goebel-Goody SM, Baum M, Paspalas CD, Fernandez SM, Carty NC, Kurup P, Lombroso PJ (2012) Therapeutic implications for striatal-enriched protein tyrosine phosphatase (STEP) in neuropsychiatric disorders. Pharmacol Rev 64:65–87

    PubMed Central  CAS  PubMed  Google Scholar 

  • Groc L, Choquet D, Stephenson FA, Verrier D, Manzoni OJ, Chavis P (2007) NMDA receptor surface trafficking and synaptic subunit composition are developmentally regulated by the extracellular matrix protein Reelin. J Neurosci 27:10165–10175

    CAS  PubMed  Google Scholar 

  • Grossman AW, Elisseou NM, McKinney BC, Greenough WT (2006) Hippocampal pyramidal cells in adult Fmr1 knockout mice exhibit an immature-appearing profile of dendritic spines. Brain Res. 1084:158–164

    CAS  PubMed  Google Scholar 

  • Guidotti A, Auta J, Davis JM, Di-Giorgi-Gerevini V, Dwivedi Y, Grayson DR, Impagnatiello F, Pandey G, Pesold C, Sharma R, Uzunov D, Costa E (2000) Decrease in Reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry 57:1061–1069

    CAS  PubMed  Google Scholar 

  • Guptill JT, Booker AB, Gibbs TT, Kemper TL, Bauman ML, Blatt GJ (2007) [3H]-flunitrazepam-labeled benzodiazepine binding sites in the hippocampal formation in autism: a multiple concentration autoradiographic study. J Autism Dev Disord 37:911–920

    PubMed  Google Scholar 

  • Hack I, Hellwig S, Junghans D, Brunne B, Bock HH, Zhao S, Frotscher M (2007) Divergent roles of ApoER2 and Vldlr in the migration of cortical neurons. Development 134:3883–3891

    CAS  PubMed  Google Scholar 

  • Hadj-Sahraoui N, Frédéric F, Delhaye-Bouchaud N, Mariani J (1996) Gender effect on Purkinje cell loss in the cerebellum of the heterozygous reeler mouse. J Neurogenet 11:45–58

    CAS  PubMed  Google Scholar 

  • Hagerman R, Lauterborn J, Au J, Berry-Kravis E (2012) Fragile X syndrome and targeted treatment trials. Results Probl Cell Differ 54:297–335

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hamburgh M (1963) Analysis of the postnatal developmental effects of “reeler,” a neurological mutation in mice. A study in developmental genetics. Dev Biol 19:165–185

    Google Scholar 

  • Han Y, Qin J, Bu DF, Chang XZ, Yang ZX (2006) Successive alterations of hippocampal gamma-aminobutyric acid B receptor subunits in a rat model of febrile seizure. Life Sci 78:2944–2952

    CAS  PubMed  Google Scholar 

  • Hatton DD, Sideris J, Skinner M, Bailey DB Jr, Roberts J, Mirrett P (2006) Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet A 140A:1804–1813

    PubMed  Google Scholar 

  • He Y, Xun G, Xia K, Hu Z, Lv L, Deng Z, Zhao J (2011) No significant association between RELN polymorphisms and autism in case-control and family-based association study in Chinese Han population. Psychiatry Res 187:462–464

    CAS  PubMed  Google Scholar 

  • Herz J, Chen Y (2006) Reelin, lipoprotein receptors and synaptic plasticity. Nat Rev Neurosci 7:850–859

    CAS  PubMed  Google Scholar 

  • Hessl D, Wang JM, Schneider A, Koldewyn K, Le L, Iwahashi C, Cheung K, Tassone F, Hagerman PJ, Rivera SM (2011) Decreased fragile X mental retardation protein expression underlies amygdala dysfunction in carriers of the fragile X premutation. Biol Psychiatry 70:859–865

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hiesberger T, Trommsdorff M, Howell BW, Goffinet A, Mumby MC, Cooper JA, Herz J (1999) Direct biding of Reelin to VLDL receptor and ApoE receptor 2 induces tyroene phosphorylation of disabled-1 and modulates tau phosphorylation. Neuron 24:481–489

    CAS  PubMed  Google Scholar 

  • Hogart A, Nagarajan RP, Patzel KA, Yasui DH, Lasalle JM (2007) 15q11–13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Hum Mol Genet 16:691–703

    PubMed Central  CAS  PubMed  Google Scholar 

  • Huber KM, Gallagher SM, Warren ST, Bear MF (2002) Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A 99:7746–7750

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ignatova N, Sindic CJM, Goffinet AM (2004) Characterization of the various farms of the Reelin protein in the cerebrospinal fluid of normal subjects and in neurological diseases. Neurobiol Dis 15:326–330

    CAS  PubMed  Google Scholar 

  • Impagnatiello F, Guidotti AR, Pesold C, Dwivedi Y, Caruncho H, Pisu MG, Uzunov DP, Smalheiser NR, Davis JM, Pandey GN, Pappas GD, Tueting T, Sharma RP, Costa E (1998) A decrease of Reelin expression as a putative vulnerability factor in schizophrenia. Proc Nat Acad Sci U S A 95:15718–15723

    CAS  Google Scholar 

  • Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, Yao WJ, Johnson M, Gunwaldsen C, Huang LY, Tang C, Shen Q, Salon JA, Morse K, Laz T, Smith KE, Nagarathnam D, Noble SA, Branchek TA, Gerald C (1998) GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature 396:674–679

    CAS  PubMed  Google Scholar 

  • Jossin Y (2008) Chemistry of Reelin. In: Fatemi SH (ed) Reelin glycoprotein: structure, biology and roles in health and disease. Springer, New York, pp 37–48

    Google Scholar 

  • Kau AS, Tierney E, Bukelis I, Stump MH, Kates WR, Trescher WH, Gray RM, Cox C, Capone GT, Stanard P (2004) Social behavior profile in young males with fragile X syndrome: characteristics and specificity. Am J Med Genet A 126A:9–17

    PubMed  Google Scholar 

  • Kauffman WE, Cortell R, Kau A, bukelis I, Tierney E, Gray R, Cox C, Capone G, Stanard P (2004) Autism spectrum disorder in fragile X syndrome: communication, social interaction, and specific behaviors. Am J Med Genet Part A 129A:225–234

    Google Scholar 

  • Kelemenova S, Schmidtova E, Ficek A, Celec P, Kubranska A, Ostatnikova D (2010) Polymorphisms of candidate genes in Slovak autism patients. Psychiatr Genet 20:137–139

    PubMed  Google Scholar 

  • Keller F, Persico AM, Zelante L, Gasperial P, D’Agruma N, Maiorano N, Totaro A, Militerni R, Bravaccio C, Wassink TH, Schneider C, Melmed R, Trillo S, Montecchi F, Palermo M, Pascucci T, Puglisi-Allegra S, Reichelt K-L, Conciatori M, Marino R, Baldi A, Quattrocchi CC (2000). Reelin gene alleles and haplotypes are associated with autistic disorder. Soc Neurosci 26:77(31.11)

    Google Scholar 

  • Kim SA, Kim JH, Park M, Cho IH, Yoo HJ (2006) Association of GABRB3 polymorphisms with autism in Korean trios. Neuropsychobiology 54:160–165

    CAS  PubMed  Google Scholar 

  • Krebs MO, Betancur C, Leroy S, Bourdel MC, Gillberg C, Leboyer M (2002) Paris Autism Research International Sibpair (PARIS) study. Absence of association between a polymorphic GGC repeat in the 5’ untranslated region of the reelin gene and autism. Mol Psychiatry 7:801–804

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kuriyama K, Hirouchi M, Kimura H (2000) Neurochemical and molecular pharmacological aspects of the GABA(B) receptor. Neurochem Res 25:1233–1239

    CAS  PubMed  Google Scholar 

  • Kwok JB, Hallupp M, Loy CT, Chan DK, Woo J, Mellick GD, Buchanan DD, Silburn PA, Halliday GM, Schofield PR (2005) GSK3B polymorphisms alter transcription and splicing in Parkinson’s disease. Ann Neurol 58:829–839

    CAS  PubMed  Google Scholar 

  • Lambert de Rouvroit C de Bergeyck V Cortvrindt C Bar I Eeckhout Y Goffinet AM (1999) Reelin, the extracellular matrix protein deficient in reeler mutant mice, is processed by a metalloproteinase. Exp Neurol 156:214–217

    CAS  PubMed  Google Scholar 

  • Li J, Nguyen L, Gleason C, Lotspeich L, Spiker D, Risch N, Myers RM (2004) Lack of evidence for an association between WNT2 and RELN polymorphisms and autism. Am J Med Genet 126B:51–57

    PubMed  Google Scholar 

  • Li H, Li Y, Shao J, Li R, Qin Y, Xie C, Zhao Z (2008) The association analysis of RELN and GRM8 genes with autistic spectrum disorder in Chinese Han population. Am J Med Genet B Neuropsychiatr Genet 147B:194–200

    CAS  PubMed  Google Scholar 

  • Li G, Jørgensen M, Campbell BM (2013) Metabotropic glutamate receptor 5-negative allosteric modulators for the treatment of psychiatric and neurological disorders (2009–July 2013). Pharm Pat Anal 2:767–802

    CAS  PubMed  Google Scholar 

  • Lugli G, Krueger JM, Davis JM, Persico AM, Keller F, Smalheiser NR (2003) Methodological factors influencing measurement and processing of plasma reelin in humans. BMC Biochem 4:9

    PubMed Central  PubMed  Google Scholar 

  • Ma DQ, Whitehead PL, Menold MM, Martin ER, Ashley-Koch AE, Mei H, Ritchie MD, Delong GR, Abramson RK, Wright HH, Cuccaro ML, Hussman JP, Gilbert JR, Pericak-Vance MA (2005) Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism. Am J Hum Genet 77:377–388

    PubMed Central  CAS  PubMed  Google Scholar 

  • Maddox LO, Menold MM, Bass MP, Rogala AR, Pericak-Vance MA, Vance JM, Gilbert JR (1999) Autistic disorder and chromosome 15q11-q13: construction and analysis of a BAC/PAC contig. Genomics 62:325–331

    CAS  PubMed  Google Scholar 

  • Marrone MC, Marinelli S, Biamonte F, Keller F, Sgobio CA, Ammassari-Teule M, Bernardi G, Mercuri NB (2006) Altered cortico-striatal synaptic plasticity and related behavioural impairments in reeler mice. Eur J Neurosci 24:2061–2070

    PubMed  Google Scholar 

  • McCauley JL, Olson LM, Delahanty R, Amin T, Nurmi EL, Organ EL, Jacobs MM, Folstein SE, Haines JL, Sutcliffe JS (2004) A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism. Am J Med Genet B Neuropsychiatr Genet 131B:51–59

    PubMed  Google Scholar 

  • McDuffie A, Abbeduto L, Lewis P, Kover S, Kim JS, Weber A, Brown WT (2010) Autism spectrum disorder in children and adolescents with fragile X syndrome: within-syndrome differences and age-related changes. Am J Intellect Dev Disabil 115:307–326

    PubMed Central  PubMed  Google Scholar 

  • Menold MM, Shao Y, Wolpert CM, Donnelly SL, Raiford KL, Martin ER, Ravan SA, Abramson RK, Wright HH, Delong GR, Cuccaro ML, Pericak-Vance MA, Gilbert JR (2001) Association analysis of chromosome 15 GABAA receptor subunit genes in autistic disorder. J Neurogenet 15:245–259

    CAS  PubMed  Google Scholar 

  • Moreno H, Borjas L, Arrieta A, Salz L, Prassad A, Estevez J, Bonilla E (1992) Clinical heterogeneity of the autistic syndrome: a study of 60 families. Invest Clin 33:13–31

    CAS  PubMed  Google Scholar 

  • Moreno-Fuenmayor H, Borjas L, Arrieta A, Valera V, Socorro-Candanoza L (1996) Plasma excitatory amino acids in autism. Invest Clin 37:113–128

    CAS  PubMed  Google Scholar 

  • Nakayama AY, Harms MB, Luo L (2000) Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons. J Neurosci 20:5329–5338

    CAS  PubMed  Google Scholar 

  • Nalavadi VC, Muddashetty RS, Gross C, Bassell GJ (2012) Dephosphorylation-induced ubiquitination and degradation of FMRP in dendrites: a role in immediate early mGluR-stimulated translation. J Neurosci 32:2582–2587

    PubMed Central  CAS  PubMed  Google Scholar 

  • Oblak AL, Gibbs TT, Blatt GJ (2010) Decreased GABA(B) receptors in the cingulate cortex and fusiform gyrus in autism. J Neurochem 114:1414–1423

    PubMed Central  CAS  PubMed  Google Scholar 

  • Oblak AL, Gibbs TT, Blatt, GJ (2011) Reduced GABA(A) receptors and benzodiazepine binding sites in the posterior cingulate cortex and fusiform gyrus in autism. Brain Res 1380:218–228

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ognibene E, Adriani W, Granstrem O, Pieretti S, Laviola G (2007) Impulsivity-anxiety-related behavior and profiles of morphine-induced analgesia in heterozygous reeler mice. Brain Res 113:173–180

    Google Scholar 

  • Persico AM, D’Agruma L, Maiorano N, Totaro A, Militerni R, Bravaccio C, Wassink TH, Schneider C, Melmed R, Trillo S, Montecchi F, Palermo M, Pascucci T, Puglisi-Allegra S, Reichelt KL, Conciatori M, Marino R, Quattrocchi CC, Baldi A, Zelante L, Gasparini P, Keller F, Collaborative Linkage Study of Autism (2001) Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry 6:150–159

    CAS  PubMed  Google Scholar 

  • Pesold C, Impagnatiello F, Pisu MG, Uzunov DP, Costa E, Guidotti A, Caruncho HJ (1998) Reelin is preferentially expressed in neurons synthesizing gamma-aminobutyric acid in cortex and hippocampus of adult rats. Proc Nat Acad Sci U S A 95:3221–3226

    CAS  Google Scholar 

  • Philofsky A, Hepburn SL, Hayes A, Hagerman RJ, Rogers SJ (2004) Linguistic and cognitive functioning and autism symptoms in young children with fragile X syndrome. Am J Ment Retard 109:208–218

    PubMed  Google Scholar 

  • Pieretti M, Zhang FP, Fu YH, Warren ST, Oostra BA, Caskey CT, Nelson DL (1991) Absence of expression of FMR-1 gene in fragile X syndrome. Cell 66:817–822

    CAS  PubMed  Google Scholar 

  • Piton A, Jouan L, Rochefort D, Dobrzeniecka S, Lachapelle K, Dion PA, Gauthier J, Rouleau GA (2013) Analysis of the effects of rare variants on splicing identifies alterations in GABA(A) receptor genes in autism spectrum disorder individuals. Eur J Hum Genet 21:749–756

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pizzarelli R, Cherubini E (2011) Alterations of GABAergic signaling in autism spectrum disorders. Neural Plast 2011:297153

    PubMed Central  PubMed  Google Scholar 

  • Podhorna J, Didriksen M (2004) The heterozygous reeler mouse: behavioural phenotype. Behav Brain Res 153:43–54

    CAS  PubMed  Google Scholar 

  • Poon PM, chen QL, Lai KY, Wong CK, Pang CP (1998) CGG repeat interruptions in the FMR1 gene in patients with infantile autism. Clin Chem Lab Med 36:649–653

    CAS  PubMed  Google Scholar 

  • Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J (2006) Synapse formation and function is modulated by the amyloid precursor protein. J Neurosci 26:7212–7221

    CAS  PubMed  Google Scholar 

  • Princivalle AP, Richards DA, Duncan JS, Spreafico R, Bowery NG (2003) Modification of GABA(B1) and GABA(B2) receptor subunits in the somatosensory cerebral cortex and thalamus of rats with absence seizures (GAERS). Epilepsy Res 55:39–51

    CAS  PubMed  Google Scholar 

  • Prosser HM, Gill CH, Hirst WD, Grau E, Robbins M, Calver A, Soffin EM, Farmer CE, Lanneau C, Gray J, Schenck E, Warmerdam BS, Clapham C, Reavill C, Rogers DC, Stean T, Upton N, Humphreys K, Randall A, Geppert M, Davies CH, Pangalos MN (2001) Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice. Mol Cell Neurosci 17:1059–1070

    CAS  PubMed  Google Scholar 

  • Qiu S, Weeber SJ (2007) Reelin signaling facilitates maturation of CA1 glutamatergic synapses. J Neurophysiol 97:2312–2321

    CAS  PubMed  Google Scholar 

  • Rojas DC, Singel D, Steinmetz S, Hepburn S, Brown MS (2013) Decreased left perisylvian GABA concentration in children with autism and unaffected siblings. Neuroimage 86:28–34

    PubMed Central  PubMed  Google Scholar 

  • Russo AJ (2013) Correlation between hepatocyte growth factor (HGF) and Gamma-aminobutyric acid (GABA) plasma levels in autistic children. Biomark Insights 8:69–75

    PubMed Central  PubMed  Google Scholar 

  • Rustan OG, Folsom TD, Yousefi MK, Fatemi SH (2013) Phosphorylated fragile X mental retardation protein at serine 499, is reduced in cerebellar vermis and superior frontal cortex of subjects with autism: implications for fragile X mental retardation protein -metabotropic glutamate receptor 5 signaling. Mol Autism 4:41

    PubMed Central  PubMed  Google Scholar 

  • Samaco RC, Hogart A, LaSalle JM (2005) Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum Mol Genet 14:483–492

    PubMed Central  CAS  PubMed  Google Scholar 

  • Schuler V, Lüscher C, Blanchet C, Klix N, Sansig G, Klebs K, Schmutz M, Heid J, Gentry C, Urban L, Fox A, Spooren W, Jaton AL, Vigouret J, Pozza M, Kelly PH, Mosbacher J, Froestl W, Käslin E, Korn R, Bischoff S, Kaupmann K, van der Putten H, Bettler B (2001) Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1)). Neuron 31:47–58

    CAS  PubMed  Google Scholar 

  • entürk A, Pfennig S, Weiss A, Burk K, Acker-Palmer A (2011) Ephrin Bs are essential components of the Reelin pathway to regulate neuronal migration. Nature 472:356-360

    Google Scholar 

  • Serajee FJ, Zhong H, Mahbubul Huq AH (2006) Association of Reelin gene polymorphisms with autism. Genomics 87:75–83

    CAS  PubMed  Google Scholar 

  • Sharma JR, Arieff Z, Gameeldien H, Davids M, Kaur M, van der Merwe L (2013) Association analysis of two single-nucleotide polymorphisms of the RELN gene with autism in the South African population. Genet Test Mol Biomarkers 17:93–98

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shimmua C, Suda S, Tsuchiya KJ, Hashimoto K, Ohno K, Matsuzaki H, Iwata K, Matsumoto K, Wakuda T, Kameno Y, Suzuki K, Tsujii M, Nakamura K, Takei N, Mori N (2011) Alteration of plasma glutamate and glutamine levels in children with high-functioning autism. PLoS One 6:e25340

    Google Scholar 

  • Shinahara K, Saijo T, Mori K, Kuroda Y (2004) Single-strand conformation polymorphism analysis of the FMR1 gene in autistic and mentally retarded children in Japan. J Med Invest 51:52–58

    PubMed  Google Scholar 

  • Shinohe A, Hashimoto K, Nakamura K, Tsujii M, Iwata Y, Tsuchiya KJ, Sekine Y, Suda S, Suzuki K, Sugihara G, Matsuzaki H, Minabe Y, Sugiyama T, Kawai M, Iyo M, Takei N, Mori N (2006) Increased serum levels of glutamate in adult patients with autism. Prog Neuropsychopharmacol Biol Psychiatry 30:1472–1477

    CAS  PubMed  Google Scholar 

  • Skaar DA, Shao Y, Haines JL, Stenger JE, Jaworski J, Martin ER, DeLong GR, Moore JH, McCauley JL, Sutcliffe JS, Ashley-Koch AE, Cuccaro ML, Folstein SE, Gilbert JR, Pericak-Vance MA (2005) Analysis of the RELN gene as a genetic risk factor for autism. Mol Psychiatry 10:563–571

    CAS  PubMed  Google Scholar 

  • Smalheiser NR, Costa E, Guidotti A, Impagnatiello F, Auta J, Lacor P, Kriho V, Pappas GD (2000) Expression of Reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells. Proc Nat Acad Sci USA 97:1281–1286

    PubMed Central  CAS  PubMed  Google Scholar 

  • Somogyi P, Tamás G, Lujan R, Buhl EH (1998) Salient features of synaptic organization in the cerebral cortex. Brain Res Brain Res Rev 26:113–135

    CAS  PubMed  Google Scholar 

  • Steiniger B, Kretschmer BD (2003) Glutamate and GABA modulate dopamine in the pedunculopontine tegmental nucleus. Exp Brain Res 149:422–430

    CAS  PubMed  Google Scholar 

  • Straessle A, Loup F, Arabadzisz D, Ohning GV, Fritschy JM (2003) Rapid and long-term alterations of hippocampal GABAB receptors in a mouse model of temporal lobe epilepsy. Eur J Neurosci 18:2213–2226

    PubMed  Google Scholar 

  • Stranahan AM, Erion JR, Wosiski-Kuhn M (2013) Reelin signaling in development, maintenance, and plasticity of neural networks. Ageing Res Rev 12:815–822

    CAS  PubMed  Google Scholar 

  • Strasser V, Fasching D, Hauser C, Mayer H, Bock HH, Hiesberger T, Herz J, Weeber EJ, Sweatt JD, Pramatarova A, Howell B, Schneider WJ, Nimpf J (2004) Receptor clustering is involved in Reelin signaling. Mol Cell Biol 24:1378–1386

    Google Scholar 

  • Szumlinski KK, Kalivas PW, Worley PF (2006) Homer proteins: implications for neuropsychiatric disorders. Curr Opin Neurobiol 16:251–257

    CAS  PubMed  Google Scholar 

  • Takahashi A, Shimamoto A, Boyson CO, DeBold JF, Miczek KA (2010) GABA(B) receptor modulation of serotonin neurons in the dorsal raphe nucleus and escalation of aggression in mice. J Neurosci 30:11771–11780

    PubMed Central  CAS  PubMed  Google Scholar 

  • Teixeira CM, Martín ED, Sahún I, Masachs N, Pujadas L, Corvelo A, Bosch C, Rossi D, Martinez A, Maldonado R, Dierssen M, Soriano E (2011) Overexpression of Reelin prevents the manifestation of behavioral phenotypes related to schizophrenia and bipolar disorder. Neuropsychopharmacology 36:2395–2405

    PubMed Central  CAS  PubMed  Google Scholar 

  • Teixeira CM, Masachs N, Muhaisen A, Bosch C, Pérez-Martínez J, Howell B, Soriano E (2014) Transient downregulation of Dab1 protein levels during development leads to behavioral and structural deficits: relevance for psychiatric disorders. Neuropsychopharmacology 39:556–568

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tian P (2012) RELN gene polymorphisms and susceptibility to autism in Chinese Han population. Neurol India 60:581–584

    PubMed  Google Scholar 

  • Tissir F, Goffinet AM (2003) Reelin and brain development. Nature Rev Neurosci 4:496–505

    CAS  Google Scholar 

  • Tochigi M, Kato C, Koishi S, Kawakubo Y, Yamamoto K, Matsumoto H, Hashimoto O, Kim SY, Watanabe K, Kano Y, Nanba E, Kato N, Sasaki T (2007) No evidence for significant association between GABA receptor genes in chromosome 15q11–q13 and autism in a Japanese population. J Hum Genet 52:985–989

    CAS  PubMed  Google Scholar 

  • Trotter J, Lee GH, Kazdoba TM, Crowell B, Domogauer J, Mahoney HM, Franco SJ, Müller U, Weeber EJ, D’Arcangelo G (2013) Dab1 is required for synaptic plasticity and associative learning. J Neurosci 33:15652–15668

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tuchman R, Rapin I (2002) Epilepsy in autism. Lancet Neurol 1:352–358

    PubMed  Google Scholar 

  • Tueting P, Costa E, Dwivedi Y, Guidotti A, Impagnatiello F, Manev R, Pesold C (1999). The phenotypic characteristics of heterozygous reeler mouse. NeuroReport 10:1327–1334

    Google Scholar 

  • Tueting P, Doueiri MS, Guidotti A, Davis JM, Costa E (2006) Reelin down-regulation in mice and psychosis endophenotypes. Neurosci Biobehav Rev 30:1065–1077

    CAS  PubMed  Google Scholar 

  • Turner PR, O’Connor K, Tate WP, Abraham WC (2003) Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 70:1–32

    CAS  PubMed  Google Scholar 

  • Ventruti A, Kazdoba TM, Niu S, D’Arcangelo G (2011) Reelin deficiency causes specific defects in the molecular composition of the synapses in the adult brain. Neuroscience 189:32–42

    CAS  PubMed  Google Scholar 

  • Vincent JB, Thevarkunnel S, Kolozsvari D, Paterson AD, Roberts W, Scherer SW (2004) Association and transmission analysis of the FMR1 IVS10 + 14C-T variant in autism. Am J Med Genet B Neuropsychiatr Genet 125B:54–56

    PubMed  Google Scholar 

  • Vincent JB, Melmer G, Bolton PF, Hodgkinson S, Holmes D, Curtis D, Gurling HM (2005) Genetic linkage analysis of the X chromosome in autism, with emphasis on the fragile X region. Psychiatr Genet 15:83–90

    PubMed  Google Scholar 

  • Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, Mill J, Cantor RM, Blencowe BJ, Geschwind DH (2011) Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474:380–384

    PubMed Central  CAS  PubMed  Google Scholar 

  • Waldmeier PC, Kaupmann K, Urwyler S (2008) Roles of GABAB receptor subtypes in presynaptic and auto- and heteroreceptor function regulating GABA and glutamate release. J Neural Transm 115:1401–1411

    CAS  PubMed  Google Scholar 

  • Weeber EJ, Beffert U, Jones C, Christian JM, Forster E, Sweatt JD, Herz J (2002) Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning. J Biol Chem 277:39944–39952

    CAS  PubMed  Google Scholar 

  • Westmark CJ, Westmark PR, Malter JS (2009) MPEP reduces seizure severity in Fmr-1 KO mice over expressing human Abeta. Int J Clin Exp Pathol 3:56–68

    PubMed  Google Scholar 

  • Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP (2005) Suppression of two major fragile X syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 49:1053–1066

    CAS  PubMed  Google Scholar 

  • Yip YP, Kronstadt-O’Brien P, Capriotti C, Cooper JA, Yip JW (2007a) Migration of sympathetic preganglionic neurons in the spinal cord is regulated by Reelin-dependent Dab1 tyrosine phosphorylation and CrkL. J Comp Neurol 502:635–643

    CAS  PubMed  Google Scholar 

  • Yip J, Soghomonian JJ, Blatt GJ (2007b) Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications. Acta Neuropathologica 113:559–568

    CAS  PubMed  Google Scholar 

  • Yip J, Soghomonian JJ, Blatt GJ (2009) Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization study. Autism Res 2:50–59

    PubMed Central  PubMed  Google Scholar 

  • Yuskaitis CJ, Mines MA, King MK, Sweatt JD, Miller CA, Jope RS (2010) Lithium ameliorates altered glycogen synthase kinase-3 and behavior in a mouse model of fragile X syndrome. Biochem Pharmacol 79:632–646

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang H, Liu X, Zhang C, Mundo E, Macciardi F, Grayson DR, Guidotti AR, Holden JJ (2002) Reelin gene alleles and susceptibility to autism spectrum disorders. Mol Psychiatry 7:1012–1017

    CAS  PubMed  Google Scholar 

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Acknowledgments

Grant support from NICHD (R01HD052074), NIMH (R01MH086000), the Bernstein Endowed Chair in Adult Psychiatry, and the Ewald Bipolar Disease Research Fund to SHF is gratefully acknowledged. Dr. Fatemi currently holds United States patents for Reelin as a diagnostic marker of autism (7341844) and as a diagnostic marker for schizophrenia, bipolar disorder, and major depression (7682805).

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  1. Department of Psychiatry, University of Minnesota School of Medicine, Minneapolis, MN, USA

    Timothy D. Folsom MS

  2. Departments of Psychiatry and Neuroscience, University of Minnesota Medical School, 420 Delaware St SE, MMC 392, 55455, Minneapolis, MN, USA

    S. Hossein Fatemi MD, PhD

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Correspondence to S. Hossein Fatemi MD, PhD .

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    S. Hossein Fatemi

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Folsom, T., Fatemi, S. (2015). Reelin, GABA, FMRP, and Autism. In: Fatemi, S. (eds) The Molecular Basis of Autism. Contemporary Clinical Neuroscience. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2190-4_16

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