Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Feature Review
  • Published:

The role of neurotrophic factors in autism

Molecular Psychiatry volume 16, pages 478–490 (2011)Cite this article

Subjects

Abstract

Autism spectrum disorders (ASDs) are pervasive developmental disorders that frequently involve a triad of deficits in social skills, communication and language. For the underlying neurobiology of these symptoms, disturbances in neuronal development and synaptic plasticity have been discussed. The physiological development, regulation and survival of specific neuronal populations shaping neuronal plasticity require the so-called ‘neurotrophic factors’ (NTFs). These regulate cellular proliferation, migration, differentiation and integrity, which are also affected in ASD. Therefore, NTFs have gained increasing attention in ASD research. This review provides an overview and explores the key role of NTFs in the aetiology of ASD. We have also included evidence derived from neurochemical investigations, gene association studies and animal models. By focussing on the role of NTFs in ASD, we intend to further elucidate the puzzling aetiology of these conditions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Di-Cicco-Bloom E, Lord C, Zwaigenbaum L, Courchesne E, Dager SR, Schmitz C et al. The developmental neurobiology of autism spectrum disorder. J Neurosci 2006; 26: 6897–6906.

    Article  CAS  Google Scholar 

  2. Volkmar FR, Pauls D . Autism. Lancet 2003; 362: 1133–1141.

    Article  PubMed  Google Scholar 

  3. Minishew NJ, Williams DL . The new neurobiology of autism: cortex, connectivity, and neuronal organization. Arch Neurol 2007; 64: 945–950.

    Article  Google Scholar 

  4. Volkmar FR, Nelson DS . Seizure disorders in autism. J Am Acad Child Adolesc Psychiatry 1990; 29: 127–129.

    Article  CAS  PubMed  Google Scholar 

  5. Quigley EM, Hurley D . Autism and the gastrointestinal tract. Am J Gastroenterol 2000; 95: 2154–2156.

    Article  CAS  PubMed  Google Scholar 

  6. Richdale AL, Prior MR . The sleep/wake rhythm in children with autism. Eur Child Adolesc Psychiatry 1995; 4: 175–186.

    Article  CAS  PubMed  Google Scholar 

  7. Shahbazian MD, Zoghbi HY . Rett syndrome and MeCP2: linking epigenetics and neuronal function. Am J Hum Genet 2002; 71: 1259–1272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Coon H . Current perspectives on the genetic analysis of autism. Am J Med Genet Semin Med Genet 2006; 142C: 24–32.

    Article  Google Scholar 

  9. Landa RJ, Holman KC, Garrett-Mayer E . Social and communication development in toddlers with early and later diagnosis of autism spectrum disorders. Arch Gen Psychiatry 2007; 64: 853–864.

    Article  PubMed  Google Scholar 

  10. Landa RJ . Diagnosis of autism spectrum disorders in the first 3 years of life. Nat Clin Pract Neurol 2008; 4: 138–147.

    Article  PubMed  Google Scholar 

  11. Lauritsen MB, Pedersen CB, Mortensen PB . Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study. J Child Psychol Psychiatr 2005; 46: 963–971.

    Article  Google Scholar 

  12. Bailey A, LeCouteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995; 25: 63–77.

    Article  CAS  PubMed  Google Scholar 

  13. Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G et al. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatr 1989; 30: 405–416.

    Article  CAS  Google Scholar 

  14. Tierney E, Nwokoro NA, Porter FD, Fruend LS, Ghuman JK, Kelley RI . Behavior phenotype in the RSH/Smith-Lemli-Opitz syndrome. Am J Med Genet 2001; 98: 191–200.

    Article  CAS  PubMed  Google Scholar 

  15. Bandim JM, Ventura LO, Miller MT, Almeida HC, Costa AE . Autism and Mobius sequence: an exploratory study of children in northeastern Brazil. Arq Neuropsiquiatr 2003; 61: 181–185.

    Article  PubMed  Google Scholar 

  16. Kolevzon A, Gross R, Reichenberg A . Prenatal and perinatal risk factors for autism: a review and integration of findings. Arch Pediatr Adolesc Med 2007; 161: 326–333.

    Article  PubMed  Google Scholar 

  17. Courchesne E, Karns CM, Davis HR, Ziccardi R, Carper RA, Tigue ZD et al. Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 2001; 57: 245–254.

    Article  CAS  PubMed  Google Scholar 

  18. Courchesne E, Carper R, Akshoomoff N . Evidence of brain overgrowth in the first year of life in autism. JAMA 2003; 290: 337–344.

    Article  PubMed  Google Scholar 

  19. Hazlett HC, Poe M, Gerig G, Smith RG, Provenzale J, Ross A et al. Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. Arch Gen Psychiatry 2005; 62: 1366–1376.

    Article  PubMed  Google Scholar 

  20. Sparks BF, Friedman SD, Shaw DW, Aylward EH, Echelard D, Artru AA et al. Brain structural abnormalities in young children with autism spectrum disorder. Neurology 2002; 59: 184–192.

    Article  CAS  PubMed  Google Scholar 

  21. Dementieva YA, Vance DD, Donnelly SL, Elston LA, Wolpert CM, Ravan SA et al. Accelerated head growth in early development of individuals with autism. Pediatr Neurol 2005; 32: 102–108.

    Article  PubMed  Google Scholar 

  22. Dissanayake C, Bui QM, Huggins R, Loesch DZ . Growth in stature and head circumference in high-functioning autism and Asperger disorder during the first 3 years of life. Dev Psychopathol 2006; 18: 381–393.

    Article  PubMed  Google Scholar 

  23. Dawson G, Munson J, Webb SJ, Nalty T, Abbott R, Toth K . Rate of head growth decelerates and symptoms worsen in the second year of life in autism. Biol Psychiatry 2007; 61: 458–464.

    Article  PubMed  Google Scholar 

  24. Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M et al. A clinicopathological study of autism. Brain 1998; 121: 889–905.

    Article  PubMed  Google Scholar 

  25. Kemper TL, Bauman M . Neuropathology of infantile autism. J Neuropathol Exp Neurol 1998; 57: 645–652.

    Article  CAS  PubMed  Google Scholar 

  26. Kemper TL, Bauman M . Neuropathology of infantile autism. Mol Psychiatry 2002; 7: S12–S13.

    Article  PubMed  Google Scholar 

  27. Lee M, Martin-Ruiz C, Graham A, Court J, Jaros E, Perry R et al. Nicotinic receptor abnormalities in the cerebellar cortex in autism. Brain 2002; 125: 1483–1495.

    Article  CAS  PubMed  Google Scholar 

  28. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA . Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005; 57: 67–81.

    Article  CAS  PubMed  Google Scholar 

  29. Ben Bashat D, Kronfeld-Duenias V, Zachor DA, Ekstein PM, Hendler T, Tarrasch R et al. Accelerated maturation of white matter in young children with autism: a high b value DWI study. Neuroimage 2007; 37: 40–47.

    Article  PubMed  Google Scholar 

  30. Bloss CS, Courchesne E . MRI neuroanatomy in young girls: a preliminary study. J Am Acad Child Adolesc Psychiatry 2007; 46: 515–523.

    Article  PubMed  Google Scholar 

  31. Carper RA, Moses P, Tigue ZD, Courchesne E . Cerebral lobes in autism: early hyperplasia and abnormal age effects. Neuroimage 2002; 16: 1038–1051.

    Article  PubMed  Google Scholar 

  32. Hazlett HC, Poe M, Gerig G, Smith RG, Piven J . Cortical white and grey brain tissue volume in adolescents and adults with autism. Biol Psychiatry 2006; 59: 1–6.

    Article  PubMed  Google Scholar 

  33. Kates WR, Burnette CP, Eliez S, Strunge LA, Kaplan D, Landa R et al. Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype in autism. Am J Psychiatry 2004; 161: 539–546.

    Article  PubMed  Google Scholar 

  34. Palmen SJ, Hulshoff Pol HE, Kemner C, Schnack HG, Durston S, Lahuis BE et al. Increased grey-matter volume in medication-naive high-functioning children with autism spectrum disorder. Psychol Med 2005; 35: 561–570.

    Article  PubMed  Google Scholar 

  35. Riikonen R, Vanhala R . Levels of cerebrospinal fluid nerve-growth factor differ in infantile autism Rett syndrome. Dev Med Child Neurol 1999; 41: 148–152.

    Article  CAS  PubMed  Google Scholar 

  36. Nelson KB, Grether JK, Croen LA, Dambrosia JM, Dickens BF, Jelliffe LL et al. Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Ann Neurol 2001; 49: 597–606.

    Article  CAS  PubMed  Google Scholar 

  37. Miyazaki K, Narita N, Sakuta R, Miyahara T, Naruse H, Okado N et al. Serum neurotrophin concentrations in autism and mental retardation: a pilot study. Brain Dev 2004; 26: 292–295.

    Article  PubMed  Google Scholar 

  38. Connolly AM, Chez M, Streif EM, Keeling RM, Golumbek PT, Kwon JM et al. Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy. Biol Psychiatry 2006; 59: 354–363.

    Article  CAS  PubMed  Google Scholar 

  39. Hashimoto K, Iwata Y, Nakamura K, Tsujii M, Tsuchiya KJ, Sekine Y et al. Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 1529–1531.

    Article  CAS  PubMed  Google Scholar 

  40. Nelson PG, Kuddo T, Song EY, Dambrosia JM, Kohler S, Satyanarayana G et al. Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory and concentrations in neonatal blood of children with autism or Down syndrome. Int J Dev Neurosci 2006; 24: 73–80.

    Article  CAS  PubMed  Google Scholar 

  41. Nishimura K, Nakamura K, Anitha A, Yamada K, Tsujii M, Iwayama Y et al. Genetic analyses of the brain-derived neurotrophic factor (BDNF) gene in autism. Biochem Biophys Res Commun 2007; 356: 200–206.

    Article  CAS  PubMed  Google Scholar 

  42. Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM et al. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science 1990; 247: 1446–1451.

    Article  CAS  PubMed  Google Scholar 

  43. Airaksinen MS, Titievsky A, Saarma M . GDNF family neurotrophic factor signaling: four masters, one servant? Mol Cell Neurosci 1999; 13: 313–325.

    Article  CAS  PubMed  Google Scholar 

  44. Barde YA . The nerve growth factor family. Prog Growth Factor Res 1990; 2: 237–248.

    Article  CAS  PubMed  Google Scholar 

  45. Götz R, Köster R, Winkler C, Raulf F, Lottspeich F, Schartl M et al. Neurotrophin-6 is a new member of the nerve growth factor family. Nature 1994; 372: 266–269.

    Article  PubMed  Google Scholar 

  46. Lindsay RM, Wiegand SJ, Altar CA, DiStefano PS . Neurotrophic factors: from molecule to man. Trends Neurosci 1994; 17: 182–190.

    Article  CAS  PubMed  Google Scholar 

  47. Barbacid M . Neurotrophic factors and their receptors. Curr Opin Cell Biol 1995; 7: 148–155.

    Article  CAS  PubMed  Google Scholar 

  48. Skaper SD . The biology of neurotrophins, signalling pathways, and functional peptide mimetics of neurotrophins and their receptors. CNS Neurol Disord Drug Targets 2008; 7: 46–62.

    Article  CAS  PubMed  Google Scholar 

  49. Avital A, Goshen I, Kamsler A, Segal M, Iverfeldt K, Richter-Levin G et al. Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus 2003; 13: 826–834.

    Article  CAS  PubMed  Google Scholar 

  50. Altar CA, Criden MR, Lindsay RM, DiStefano PS . Characterization and topography of high-affinity 125I-neurotrophin-3 binding to mammalian brain. J Neurosci 1993; 13: 733–743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Durany N, Michel T, Kurt J, Cruz-Sánchez FF, Cervós-Navarro J, Riederer P . Brain-derived neurotrophic factor and neurotrophin-3 levels in Alzheimer's disease brains. Int J Dev Neurosci 2000; 18: 807–813.

    Article  CAS  PubMed  Google Scholar 

  52. Seidah NG, Benjannet S, Pareek S, Chrétien M, Murphy RA . Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases. FEBS Lett 1996; 379: 247–250.

    Article  CAS  PubMed  Google Scholar 

  53. Seidah NG, Benjannet S, Pareek S, Savaria D, Hamelin J, Goulet B et al. Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertases. Biochem J 1996; 314: 951–960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Michalski B, Fahnestock M . Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease. Brain Res Mol Brain Res 2003; 111: 148–154.

    Article  CAS  PubMed  Google Scholar 

  55. Peng S, Wuu J, Mufson EJ, Fahnestock M . Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease. J Neurochem 2005; 93: 1412–1421.

    Article  CAS  PubMed  Google Scholar 

  56. Lee R, Kermani P, Teng KK, Hempstead BL . Regulation of cell survival by secreted proneurotrophins. Science 2001; 294: 1945–1948.

    Article  CAS  PubMed  Google Scholar 

  57. Rodríguez-Tébar A, Dechant G, Götz R, Barde YA . Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. EMBOJ 1992; 11: 917–922.

    Article  Google Scholar 

  58. Dechant G, Rodríguez-Tébar A, Barde YA . Neurotrophin receptors. Prog Neurobiol 1994; 42: 347–352.

    Article  CAS  PubMed  Google Scholar 

  59. Dechant G, Biffo S, Okazawa H, Kolbeck R, Pottgiesser J, Barde YA . Expression and binding characteristics of the BDNF receptor chick trkB. Development 1993; 119: 545–558.

    CAS  PubMed  Google Scholar 

  60. Mahadeo D, Kaplan L, Chao MV, Hempstead BL . High affinity nerve growth factor binding displays a faster rate of association than p140trk binding. Implications for multi-subunit polypeptide receptors. J Biol Chem 1994; 269: 6884–6891.

    CAS  PubMed  Google Scholar 

  61. Schröpel A, von Schack D, Dechant G, Barde YA . Early expression of the nerve growth factor receptor ctrkA in chick sympathetic and sensory ganglia. Mol Cell Neurosci 1995; 6: 544–566.

    Article  PubMed  Google Scholar 

  62. Chao MV . The p75 neurotrophin receptor. J Neurobiol 1994; 25: 1373–1385.

    Article  CAS  PubMed  Google Scholar 

  63. Arevalo JC, Conde B, Hempstead BL, Chao MV, Martin-Zanca D, Perez P . TrkA immunoglobulin-like ligand binding domains inhibit spontaneous activation of the receptor. Mol Cell Biol 2000; 20: 5908–5916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Esposito D, Patel P, Stephens RM, Perez P, Chao MV, Kaplan DR et al. The cytoplasmic and transmembrane domains of the p75 and Trk A receptors regulate high affinity binding to nerve growth factor. J Biol Chem 2001; 276: 32687–32695.

    Article  CAS  PubMed  Google Scholar 

  65. Kaplan DR, Miller FD . Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol 2000; 10: 381–391.

    Article  CAS  PubMed  Google Scholar 

  66. Ravichandran KS . Signaling via Shc family adapter proteins. Oncogene 2001; 20: 6322–6330.

    Article  CAS  PubMed  Google Scholar 

  67. York RD, Yao H, Dillon T, Ellig CL, Eckert SP, McCleskey EW et al. Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature 1998; 392: 622–626.

    Article  CAS  PubMed  Google Scholar 

  68. Lonze BE, Ginty DD . Function and regulation of CREB family transcription factors in the nervous system. Neuron 2002; 35: 605–623.

    Article  CAS  PubMed  Google Scholar 

  69. Wymann MP, Pirola L . Structure and function of phosphoinositide 3-kinases. Biochim Biophys Acta 1998; 1436: 127–150.

    Article  CAS  PubMed  Google Scholar 

  70. Chao MV . Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 2003; 4: 299–309.

    Article  CAS  PubMed  Google Scholar 

  71. Roux PP, Barker PA . Neurotrophin signaling through the p75 neurotrophin receptor. Prog Neurobiol 2002; 67: 203–233.

    Article  CAS  PubMed  Google Scholar 

  72. Dowling P, Ming X, Raval S, Husar W, Casaccia-Bonnefil P, Chao M et al. Up-regulated p75NTR neurotrophin receptor on glial cells in MS plaques. Neurology 1999; 53: 1676–1682.

    Article  CAS  PubMed  Google Scholar 

  73. Roux PP, Colicos MA, Barker PA, Kennedy TE . p75 neurotrophin receptor expression is induced in apoptotic neurons after seizure. J Neurosci 1999; 19: 6887–6896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Beattie MS, Harrington AW, Lee R, Kim JY, Boyce SL, Longo FM et al. ProNGF induces p75-mediated death of oligodendrocytes following spinal cord injury. Neuron 2002; 36: 375–386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Majdan M, Miller FD . Neuronal life and death decisions functional antagonism between the Trk and p75 neurotrophin receptors. Int J Dev Neurosci 1999; 17: 153–161.

    Article  CAS  PubMed  Google Scholar 

  76. Kang H, Schuman EM . A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science 1996; 273: 1402–1406.

    Article  CAS  PubMed  Google Scholar 

  77. Levine ES, Dreyfus CF, Black IB, Plummer MR . Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors. Proc Natl Acad Sci USA 1995; 92: 8074–8077.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T . Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci USA 1995; 92: 8856–8860.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Xie CW, Sayah D, Chen QS, Wei WZ, Smith D, Liu X . Deficient long-term memory and long-lasting long-term potentiation in mice with a targeted deletion of neurotrophin-4 gene. Proc Natl Acad Sci USA 2000; 97: 8116–8121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Yang F, He X, Feng L, Mizuno K, Liu XW, Russell J et al. PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation. Nat Neurosci 2001; 4: 19–28.

    Article  CAS  PubMed  Google Scholar 

  81. Croen LA, Goines P, Braunschweig D, Yolken R, Yoshida CK, Grether JK et al. Brain-derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) Study. Autism Res 2008; 1: 130–137.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Katoh-Semba R, Wakako R, Komori T, Shigemi H, Miyazaki N, Ito H et al. Age-related changes in BDNF protein levels in human serum: differences between autism cases and normal controls. Int J Dev Neurosci 2007; 25: 367–372.

    Article  CAS  PubMed  Google Scholar 

  83. Lang UE, Hellweg R, Sander T, Gallinat J . The Met allele of the BDNF Val66Met polymorphism is associated with increased BDNF serum concentrations. Mol Psychiatry 2009; 14: 120–122.

    Article  CAS  PubMed  Google Scholar 

  84. Shimizu E, Hashimoto K, Iyo M . Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: the possibility to explain ethnic mental traits. Am J Med Genet B Neuropsychiatr Genet 2004; 126B: 122–123.

    Article  PubMed  Google Scholar 

  85. Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M . WAGR syndrome: a clinical review of 54 cases. Pediatrics 2005; 116: 984–988.

    Article  PubMed  Google Scholar 

  86. Xu S, Han JC, Morales A, Menzie CM, Williams K, Fan YS . Characterization of 11p14-p12 deletion in WAGR syndrome by array CGH for identifying genes contributing to mental retardation and autism. Cytogenet Genome Res 2008; 122: 181–187.

    Article  CAS  PubMed  Google Scholar 

  87. Riikonen R . Neurotrophic factors in the pathogenesis of Rett syndrome. J Child Neurol 2003; 18: 693–697.

    Article  PubMed  Google Scholar 

  88. Moses HL, Branum EL, Proper JA, Robinson RA . Transforming growth factor production by chemically transformed cells. Cancer Res 1981; 41: 2842–2848.

    CAS  PubMed  Google Scholar 

  89. Shi Y, Massagué J . Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003; 113: 685–700.

    Article  CAS  PubMed  Google Scholar 

  90. Nickl-Jockschat T, Arslan F, Doerfelt A, Bogdahn U, Bosserhoff A, Hau P . An imbalance between Smad and MAPK pathways is responsible for TGF-beta tumor promoting effects in high-grade gliomas. Int J Oncol 2007; 30: 499–507.

    CAS  PubMed  Google Scholar 

  91. Okada K, Hashimoto K, Iwata Y, Nakamura K, Tsujii M, Tsuchiya KJ et al. Decreased serum levels of transforming growth factor-beta1 in patients with autism. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31: 187–190.

    Article  CAS  PubMed  Google Scholar 

  92. Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen RL, Croen LA et al. Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. J Neuroimmunol 2008; 204: 149–153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Toyoda T, Nakamura K, Yamada K, Thanseem I, Anitha A, Suda S et al. SNP analyses of growth factor genes EGF, TGFbeta-1, and HGF reveal haplotypic association of EGF with autism. Biochem Biophys Res Commun 2007; 360: 715–720.

    Article  CAS  PubMed  Google Scholar 

  94. Mozell RL, McMorris FA . Insulin-like growth factor I stimulates oligodendrocyte development and myelination in rat brain aggregate cultures. J Neurosci Res 1991; 30: 382–390.

    Article  CAS  PubMed  Google Scholar 

  95. Barres BA, Hart IK, Coles HS, Burne JF, Voyvodic JT, Richardson WD et al. Cell death and control of cell survival in the oligodendrocyte lineage. Cell 1992; 70: 31–46.

    Article  CAS  PubMed  Google Scholar 

  96. Werther GA, Russo V, Baker N, Butler G . The role of the insulin-like growth factor system in the developing brain. Horm Res 1998; 49: 37–40.

    Article  CAS  PubMed  Google Scholar 

  97. D′Mello SR, Borodezt K, Soltoff SP . Insulin-like growth factor and potassium depolarization maintain neuronal survival by distinct pathways: possible involvement of PI 3-kinase in IGF-1 signaling. J Neurosci 1997; 17: 1548–1560.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Beck KD, Powell-Braxton L, Widmer HR, Valverde J, Hefti F . Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons. Neuron 1995; 14: 717–730.

    Article  CAS  PubMed  Google Scholar 

  99. Riikonen R, Makkonen I, Vanhala R, Turpeinen U, Kuikka J, Kokki H . Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autism. Dev Med Child Neurol 2006; 48: 751–755.

    Article  PubMed  Google Scholar 

  100. Courchesne E, Pierce K, Schumann CM, Redcay E, Buckwalter JA, Kennedy DP et al. Mapping early brain development in autism. Neuron 2007; 56: 399–413.

    Article  CAS  PubMed  Google Scholar 

  101. Mills JL, Hediger ML, Molloy CA, Chrousos GP, Manning-Courtney P, Yu KF et al. Elevated levels of growth-related hormones in autism and autism spectrum disorder. Clin Endocrinol (Oxf) 2007; 67: 230–237.

    Article  CAS  Google Scholar 

  102. Fall CH, Clark PM, Hindmarsh PC, Clayton PE, Shiell AW, Law CM . Urinary GH and IGF-I excretion in nine year-old children: relation to sex, current size and size at birth. Clin Endocrinol (Oxf) 2000; 53: 69–76.

    Article  CAS  Google Scholar 

  103. Yamada M, Ikeuchi T, Hatanaka H . The neurotrophic action and signalling of epidermal growth factor. Prog Neurobiol 1997; 51: 19–37.

    Article  CAS  PubMed  Google Scholar 

  104. Suzuki K, Hashimoto K, Iwata Y, Nakamura K, Tsujii M, Tsuchiya KJ et al. Decreased serum levels of epidermal growth factor in adult subjects with high-functioning autism. Biol Psychiatry 2007; 62: 267–269.

    Article  CAS  PubMed  Google Scholar 

  105. Kohler N, Lipton A . Platelets as a source of fibroblast growth-promoting activity. Exp Cell Res 1974; 87: 297–301.

    Article  CAS  PubMed  Google Scholar 

  106. Westermark B, Wasteson A . The response of cultured human normal glial cells to growth factors. Adv Metab Disord 1975; 8: 85–100.

    Article  CAS  PubMed  Google Scholar 

  107. Reddy UR, Pleasure D . Expression of platelet-derived growth factor (PDGF) and PDGF receptor genes in the developing rat brain. J Neurosci Res 1992; 31: 670–677.

    Article  CAS  PubMed  Google Scholar 

  108. Li WM, Huang WQ, Huang YH, Jiang DZ, Wang QR . Positive and negative hematopoietic cytokines produced by bone marrow endothelial cells. Cytokine 2000; 12: 1017–1023.

    Article  CAS  PubMed  Google Scholar 

  109. Bergsten E, Uutela M, Li X, Pietras K, Ostman A, Heldin CH et al. PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat Cell Biol 2001; 3: 512–516.

    Article  CAS  PubMed  Google Scholar 

  110. LaRochelle WJ, Jeffers M, McDonald WF, Chillakuru RA, Giese NA, Lokker NA et al. PDGF-D, a new protease-activated growth factor. Nat Cell Biol 2001; 3: 517–521.

    Article  CAS  PubMed  Google Scholar 

  111. Fredriksson L, Li H, Eriksson U . The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Rev 2004; 15: 197–204.

    Article  CAS  PubMed  Google Scholar 

  112. Kwon YK . Effect of neurotrophic factors on neuronal stem cell death. J Biochem Mol Biol 2002; 35: 87–93.

    CAS  PubMed  Google Scholar 

  113. Sung JY, Lee SY, Min DS, Eom TY, Ahn YS, Choi MU et al. Differential activation of phospholipases by mitogenic EGF and neurogenic PDGF in immortalized hippocampal stem cell lines. J Neurochem 2001; 78: 1044–1053.

    Article  CAS  PubMed  Google Scholar 

  114. Kajizuka M, Miyachi T, Matsuzaki H, Iwata K, Shinmura C, Suzuki K et al. Serum levels of platelet-derived growth factor BB homodimers are increased in male children with autism. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 154–158.

    Article  CAS  PubMed  Google Scholar 

  115. Weijers HG, Wiesbeck GA, Wodarz N, Keller H, Michel T, Böning J . Gender and personality in alcoholism. Arch Womens Ment Health 2003; 6: 245–255.

    Article  PubMed  Google Scholar 

  116. Wiesbeck GA, Weijers HG, Wodarz N, Hermann M, Johann M, Keller H et al. Dopamin D 2 (DAD 2) and dopamin D 3 (DAD 3) receptor gene polymorphismus and treatment outcome in alcohol dependence. J Neural Transm 2003; 110: 813–820.

    CAS  PubMed  Google Scholar 

  117. Wiesbeck GA, Weijers HG, Wodarz N, Keller HK, Michel TM, Herrmann MJ et al. Serotonin transporter gene polymorphism and personality traits in primary alcohol dependence. World J Biol Psychiatry 2004; 5: 42–45.

    Article  Google Scholar 

  118. Ettinger U, Kumari V, Collier DA, Powell J, Luzi S, Michel TM et al. Catechol-O-methyltransferase (COMT) Val 158 Met genotype is associated with BOLD response as a function of task characteristic. Neuropsychopharmacology 2008; 33: 3046–3057.

    Article  CAS  PubMed  Google Scholar 

  119. Sheldrick AJ, Krug A, Markov V, Leube D, Michel TM, Zerres K et al. Effect of COMT val158met genotype on cognition and personality. Eur Psychiatry 2008; 23: 385–389.

    Article  CAS  PubMed  Google Scholar 

  120. Nickl-Jockschat T, Rietschel M, Kircher T . Korrelation zwischen Risikogenvarianten für Schizophrenie und Hirnstrukturanomalien. Nervenarzt 2009; 80: 40–53.

    Article  CAS  PubMed  Google Scholar 

  121. Nickl-Jockschat T, Michel TM . Genetische und hirnstrukturelle Anomalien bei Autismus Spektrum-Störungen: eine Brücke zum Verständnis der Ätiopathogenese. Nervenarzt 2010; e-pub first: doi:10.1007/so0115-010-2989-5.

  122. Autism Genome Project Consortium. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 2007; 39: 319–328.

    Article  CAS  Google Scholar 

  123. Sadakata T, Mizoguchi A, Sato Y, Katoh-Semba R, Fukuda M, Mikoshiba K et al. The secretory granule-associated protein CAPS2 regulates neurotrophin release and cell survival. J Neurosci 2004; 24: 43–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Sadakata T, Washida M, Iwayama Y, Shoji S, Sato Y, Ohkura T et al. Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients. J Clin Invest 2007; 117: 931–943.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Sadakata T, Kakegawa W, Mizoguchi A, Washida M, Katoh-Semba R, Shutoh F et al. Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release. J Neurosci 2007; 27: 2472–2482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY . Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999; 23: 185–188.

    Article  CAS  PubMed  Google Scholar 

  127. Kumar A, Kamboj S, Malone BM, Kudo S, Twiss JL, Czymmek KJ et al. Analysis of protein domains and Rett syndrome mutations indicate that multiple regions influence chromatin-binding dynamics of the chromatin-associated protein MECP2 in vivo. J Cell Sci 2008; 121: 1128–1137.

    Article  CAS  PubMed  Google Scholar 

  128. Yasui DH, Peddada S, Bieda MC, Vallero RO, Hogart A, Nagarajan RP et al. Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc Natl Acad Sci USA 2007; 104: 19416–19421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 2008; 320: 1224–1229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 2003; 302: 885–889.

    Article  CAS  PubMed  Google Scholar 

  131. Zhou Z, Hong EJ, Cohen S, Zhao WN, Ho HY, Schmidt L et al. Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron 2006; 52: 255–269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 2003; 302: 890–893.

    Article  CAS  PubMed  Google Scholar 

  133. Abrahams BS, Geschwind DH . Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008; 9: 341–355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Nagarajan RP, Hogart AR, Gwye Y, Martin MR, LaSalle JM . Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics 2006; 1: e1–11.

    Article  PubMed  Google Scholar 

  135. 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; 18: 525–534.

    Article  CAS  PubMed  Google Scholar 

  136. Sng JC, Taniura H, Yoneda Y . A tale of early response genes. Biol Pharm Bull 2004; 27: 606–612.

    Article  CAS  PubMed  Google Scholar 

  137. Glorioso C, Sabatini M, Unger T, Hashimoto T, Monteggia LM, Lewis DA et al. Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood. Mol Psychiatry 2006; 11: 633–648.

    Article  CAS  PubMed  Google Scholar 

  138. Adegbola A, Gao H, Sommer S, Browning M . A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD). Am J Med Genet A 2008; 146A: 505–511.

    Article  CAS  PubMed  Google Scholar 

  139. Christensen J, Agger K, Cloos PA, Pasini D, Rose S, Sennels L et al. RBP2 belongs to a family of demethylases, specific for tri- and dimethylated lysine 4 on histone 3. Cell 2007; 128: 1063–1076.

    Article  CAS  PubMed  Google Scholar 

  140. Iwase S, Lan F, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH et al. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 2007; 128: 1077–1088.

    Article  CAS  PubMed  Google Scholar 

  141. Durany N, Michel T, Zochling R, Boissl KW, Cruz-Sanchez FF, Riederer P et al. Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses. Schizophr Res 2001; 52: 79–86.

    Article  CAS  PubMed  Google Scholar 

  142. Enstrom A, Onore C, Tarver A, Herzt-Picciotto I, Hansen R, Croen L et al. Peripheral blood leukocyte production of BDNF following mitogen stimulation in early onset and regressive autism. Am J Biochem Biotechnol 2008; 4: 121–129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. O′Hearn K, Asato M, Ordaz S, Luna B . Neurodevelopment and executive function in autism. Dev Psychopathol 2008; 20: 1103–1132.

    Article  PubMed  Google Scholar 

  144. Müller RA . From loci to networks and back again: anomalies in the study of autism. Ann NY Acad Sci 2008; 1145: 300–315.

    Article  PubMed  Google Scholar 

  145. Verhoeven JS, De Cock P, Lagae L, Sunaert S . Neuroimaging of autism. Neuroradiology 2010; 52: 3–14.

    Article  PubMed  Google Scholar 

  146. Barnea-Goraly N, Kwon H, Menon V, Eliez S, Lotspeich L, Reiss AL . White matter structure in autism: preliminary evidence from diffusion tensor imaging. Biol Psychiatry 2004; 55: 323–326.

    Article  PubMed  Google Scholar 

  147. Alexander AL, Lee JE, Lazar M, Boudos R, DuBray MB, Oakes TR et al. Diffusion tensor imaging of the corpus callosum in AUTISM. Neuroimage 2007; 34: 61–73.

    Article  PubMed  Google Scholar 

  148. Sundaram SK, Kumar A, Makki MI, Behen ME, Chugani HT, Chugani DC . Diffusion tensor imaging of frontal lobe in autism spectrum disorder. Cereb Cortex 2008; 18: 2659–2665.

    Article  PubMed  PubMed Central  Google Scholar 

  149. Lee JE, Bigler ED, Alexander AL, Lazar M, DuBray MB, Chung MK et al. Diffusion tensor imaging of white matter in the superior temporal gyrus and temporal stem in autism. Neurosci Lett 2007; 424: 127–132.

    Article  CAS  PubMed  Google Scholar 

  150. Keller TA, Kana RK, Just MA . A developmental study of the structural integrity of white matter in autism. Neurosci Lett 2007; 424: 127–132.

    Article  CAS  Google Scholar 

  151. Dawson G, Webb S, Schellenberg GD, Dager S, Friedman S, Aylward E et al. Defining the broader phenotype of autism: genetic, brain, and behavioral perspectives. Dev Psychopathol 2002; 14: 581–611.

    Article  PubMed  Google Scholar 

  152. Bennetto L, Pennington BF, Rogers SJ . Intact and impaired memory functions in autism. Child Dev 1996; 67: 1816–1835.

    Article  CAS  PubMed  Google Scholar 

  153. Luna B, Doll SK, Hegedus SJ, Minshew NJ, Sweeney JA . Maturation of executive function in autism. Biol Psychiatry 2007; 61: 474–481.

    Article  PubMed  Google Scholar 

  154. Ozonoff S, Cook I, Coon H, Dawson G, Joseph RM, Klin A et al. Performance on Cambridge Neuropsychological Test Automated Battery subtests sensitive to frontal lobe function in people with autistic disorder: evidence from the Collaborative Programs of Excellence in Autism network. J Autism Dev Disord 2004; 34: 139–150.

    Article  PubMed  Google Scholar 

  155. Volkmar F, Chawarska K, Klin A . Autism in infancy and early childhood. Annu Rev Psychol 2005; 56: 315–336.

    Article  PubMed  Google Scholar 

  156. Kana RK, Keller TA, Minshew NJ, Just MA . Inhibitory control in high-functioning autism: decreased activation and underconnectivity in inhibition networks. Biol Psychiatry 2007; 62: 198–206.

    Article  PubMed  Google Scholar 

  157. Just MA, Cherkassky VL, Keller TA, Minshew NJ . Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. Brain 2004; 127: 1811–1821.

    Article  PubMed  Google Scholar 

  158. Koshino H, Carpenter PA, Minshew NJ, Cherkassky VL, Keller TA, Just MA . Functional connectivity in an fMRI working memory task in high-functioning autism. Neuroimage 2005; 24: 810–821.

    Article  PubMed  Google Scholar 

  159. Koshino H, Kana RK, Keller TA, Cherkassky VL, Minshew NJ, Just MA . fMRI investigation of working memory for faces in autism: visual coding and underconnectivity with frontal areas. Cereb Cortex 2008; 18: 289–300.

    Article  PubMed  Google Scholar 

  160. Erickson KI, Kim JS, Suever BL, Voss MW, Francis BM, Kramer AF . Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms. Front Hum Neurosci 2008; 2: 11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. Raz N, Rodrigue KM, Kennedy KM, Land S . Genetic and vascular modifiers of age-sensitive cognitive skills: effects of COMT, BDNF, ApoE, and hypertension. Neuropsychology 2009; 23: 105–116.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Sakata K, Woo NH, Martinowich K, Greene JS, Schloesser RJ, Shen L et al. Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex. Proc Natl Acad Sci USA 2009; 106: 5942–5947.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Moy SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson TR et al. Sociability and preference for social novelty in five inbred strains: an approach to assess autistic–like behavior in mice. Genes Brain Behav 2004; 3: 287–302.

    Article  CAS  PubMed  Google Scholar 

  164. Moy SS, Nadler JJ, Young NB, Perez A, Holloway LP, Barbaro RP et al. Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains. Behav Brain Res 2007; 176: 4–20.

    Article  PubMed  Google Scholar 

  165. Lewis MH, Tanimura Y, Lee LW, Bodfish JW . Animal models of restricted repetitive behavior in autism. Behav Brain Res 2007; 176: 66–74.

    Article  PubMed  Google Scholar 

  166. Branchi I, Ricceri L . Transgenic and knock-out mouse pups: the growing need for behavioral analysis. Genes Brain Behav 2002; 1: 135–141.

    Article  CAS  PubMed  Google Scholar 

  167. Branchi I, D′Andrea I, Sietzema J, Fiore M, Di Fausto V, Aloe L et al. Early social enrichment augments adult hippocampal BDNF levels and survival of BrdU-positive cells while increasing anxiety- and ‘depression’-like behavior. J Neurosci Res 2006; 83: 965–973.

    Article  CAS  PubMed  Google Scholar 

  168. Ricceri L, Moles A, Crawley J . Behavioral phenotyping of mouse models of neurodevelopmental disorders: relevant social behavior patterns across the life span. Behav Brain Res 2007; 176: 40–52.

    Article  PubMed  Google Scholar 

  169. Moy SS, Nadler JJ . Advances in behavioral genetics: mouse models of autism. Mol Psychiatry 2008; 13: 4–26.

    Article  CAS  PubMed  Google Scholar 

  170. Picker JD, Yang R, Ricceri L, Berger-Sweeney J . An altered neonatal behavioral phenotype in Mecp2 mutant mice. NeuroReport 2006; 17: 541–544.

    Article  PubMed  Google Scholar 

  171. Moles A, Kieffer BL, D′Amato FR . Deficit in attachment behavior in mice lacking the mu-opioid receptor gene. Science 2004; 304: 1983–1986.

    Article  CAS  PubMed  Google Scholar 

  172. Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 2006; 314: 140–143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Thome J, Nara K, Foley P, Michel T, Gsell W, Retz W et al. CNTF genotypes: influence on choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) activities and neurotrophin 3 (NT3) concentration in human post mortem brain tissue. J Brain Res 1997; 38: 443–445.

    CAS  Google Scholar 

  174. Michel TM, Frangou S, Camara S, Thiemeyer D, Jecel J, Tatschner T et al. Altered glial cell line-derived neurotrophic factor (GDNF) concentrations in the brain of patients with depressive disorder: a comparative post-mortem study. Eur Psychiatry 2008; 23: 413–420.

    Article  PubMed  Google Scholar 

  175. Kaartinen V, Voncken JW, Shuler C, Warburton D, Bu D, Heisterkamp N et al. Abnormal lung development and cleft palate in mice lacking TGF-beta3 indicates defects of epithelial-mesenchymal interaction. Nat Genet 1995; 11: 415–421.

    Article  CAS  PubMed  Google Scholar 

  176. Kulkarni AB, Karlsson S . Transforming growth factor-beta 1 knockout mice. Am J Pathol 1993; 143: 3–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Sanford LP, Ormsby I, Gittenberger-de Groot AC, Sariola H, Friedman R, Biovin GP et al. TGF-β2 knockout mice have multiple developmental defects that are non-overlapping with other TGF-β knockout phenotypes. Development 1997; 124: 2656–2670.

    Google Scholar 

  178. Arslan F, Bosserhoff AK, Nickl-Jockschat T, Doerfelt A, Bogdahn U, Hau P . The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-beta2. Br J Cancer 2007; 96: 1560–1568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Brkanac Z, Raskind WH, King BH . Pharmacology and genetics of autism: implications for diagnosis and treatment. Per Med 2008; 5: 599–607.

    Article  PubMed  PubMed Central  Google Scholar 

  180. Correia CT, Almeida JP, Santos PE, Sequeira AF, Marques CE, Miguel TS et al. Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions. Pharmacogenomics J 2009.

  181. Tsai SJ . TrkB partial agonists: potential treatment strategy for major depression. Med Hypotheses 2007; 68: 674–676.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany

    T Nickl-Jockschat & T M Michel

Authors
  1. T Nickl-Jockschat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T M Michel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T M Michel.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nickl-Jockschat, T., Michel, T. The role of neurotrophic factors in autism. Mol Psychiatry 16, 478–490 (2011). https://doi.org/10.1038/mp.2010.103

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2010.103

Keywords

This article is cited by

Search

Advanced search

Quick links