Skip to main content
SpringerLink
Log in

Neurotrophic Factors in Autism Spectrum Disorders

  • Reference work entry
Comprehensive Guide to Autism

  • 360 Accesses

Abstract

A variety of evidence from both micro- and macroanatomy, as well as from functional imaging studies, hint at changes in cerebral connectivity and impairments of synaptic plasticity as central pathomechanisms in autism. The molecular basis of these pathologies is not well understood up to now. Neurotrophic factors (NTF) are one of the most prominent mechanisms influencing the development and maintenance of the central nervous system, playing a key role in brain development and maintenance of neurons, and are able to critically influence the formation and elimination of neuronal connections. Thus, they are promising candidates for influencing autism pathophysiology.

This chapter aims to give an overview over the current literature on neurotrophic factors and autism. Both molecular genetic findings and protein level changes suggest an involvement of NTFs in autism pathophysiology. A better understanding of their role seems to be a promising approach not only for a more comprehensive view of autism itself but also a potentially important step towards the development of new diagnostic and therapeutic approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,199.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 1,299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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;204:149–53.

    Article  PubMed  Google Scholar 

  • Autism Genome Project Consortium. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet. 2007;39:319–28.

    Article  Google Scholar 

  • 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;13:826–34.

    Article  PubMed  Google Scholar 

  • 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;55:323–6.

    Article  PubMed  Google Scholar 

  • 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;14:717–30.

    Article  PubMed  Google Scholar 

  • Chao MV. The p75 neurotrophin receptor. J Neurobiol. 1994;25:1373–85.

    Article  PubMed  Google Scholar 

  • 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;59:354–63.

    Article  PubMed  Google Scholar 

  • Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA. 2003;290:337–44.

    Article  PubMed  Google Scholar 

  • 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;1:130–7.

    Article  PubMed  Google Scholar 

  • Dechant G, Rodríguez-Tébar A, Barde YA. Neurotrophin receptors. Prog Neurobiol. 1994;42:347–52.

    Article  PubMed  Google Scholar 

  • 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;32:102–8.

    Article  PubMed  Google Scholar 

  • 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  Google Scholar 

  • 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;11:633–48.

    Article  PubMed  Google Scholar 

  • Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736.

    Article  PubMed  Google Scholar 

  • 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;34:154–8.

    Article  PubMed  Google Scholar 

  • 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;25:367–72.

    Article  PubMed  Google Scholar 

  • Kemper TL, Bauman M. Neuropathology of infantile autism. Mol Psychiatry. 2002;7:S12–3.

    Article  PubMed  Google Scholar 

  • Lee R, Kermani P, Teng KK, Hempstead BL. Regulation of cell survival by secreted proneurotrophins. Science. 2001;294:1945–8.

    Article  PubMed  Google Scholar 

  • Lonze BE, Ginty DD. Function and regulation of CREB family transcription factors in the nervous system. Neuron. 2002;35:605–23.

    Article  PubMed  Google Scholar 

  • 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;67:230–7.

    Article  Google Scholar 

  • Moses HL, Branum EL, Proper JA, Robinson RA. Transforming growth factor production by chemically transformed cells. Cancer Res. 1981;41:2842–8.

    PubMed  Google Scholar 

  • 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 

  • 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  PubMed  Google Scholar 

  • 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  PubMed  Google Scholar 

  • Nickl-Jockschat T, Michel TM. The role of neurotrophic factors in autism. Mol Psychiatry. 2011a;16:478–90.

    Article  PubMed  Google Scholar 

  • Nickl-Jockschat T, Michel TM. Genetische und hirnstrukturelle anomalien bei autismus spektrum-störungen: eine brücke zum verständnis der ätiopathogenese. Nervenarzt. 2011b;82(5):618–27.

    Article  PubMed  Google Scholar 

  • Nickl-Jockschat T, Habel U, Michel TM, Manning J, Laird AR, Fox PT, et al. Brain structure anomalies in autism spectrum disorder – a meta-analysis of VBM studies using anatomic likelihood estimation. Hum Brain Mapp. 2012;33(6):1470–89.

    Article  PubMed  Google Scholar 

  • 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;356:200–6.

    Article  PubMed  Google Scholar 

  • O’Hearn K, Asato M, Ordaz S, Luna B. Neurodevelopment and executive function in autism. Dev Psychopathol. 2008;20:1103–32.

    Article  PubMed  Google Scholar 

  • 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;48:751–5.

    Article  PubMed  Google Scholar 

  • 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. 2007a;117:931–43.

    Article  PubMed  Google Scholar 

  • 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. 2007b;27:2472–82.

    Article  PubMed  Google Scholar 

  • 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;379:247–50.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • 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;62:267–9.

    Article  PubMed  Google Scholar 

  • 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;18:525–34.

    Article  PubMed  Google Scholar 

  • 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;360:715–20.

    Article  PubMed  Google Scholar 

  • Tsai SJ. TrkB partial agonists: potential treatment strategy for major depression. Med Hypotheses. 2007;68:674–6.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • 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  PubMed  Google Scholar 

  • Wymann MP, Pirola L. Structure and function of phosphoinositide 3-kinases. Biochim Biophys Acta. 1998;1436:127–50.

    Article  PubMed  Google Scholar 

  • 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;122:181–7.

    Article  PubMed  Google Scholar 

  • 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;52:255–69.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Thomas Nickl-Jockschat

Authors
  1. Thomas Nickl-Jockschat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Nickl-Jockschat .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, Faculty of Science & Technology, London, United Kingdom

    Vinood B. Patel

  2. Nutritional Sciences Division and Genomics Centre, King's College London, London, United Kingdom

    Victor R. Preedy

  3. Faculty of Society and Health, Buckinghamshire New University, Middlesex, United Kingdom

    Colin R. Martin

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this entry

Cite this entry

Nickl-Jockschat, T. (2014). Neurotrophic Factors in Autism Spectrum Disorders. In: Patel, V., Preedy, V., Martin, C. (eds) Comprehensive Guide to Autism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4788-7_36

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-4788-7_36

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-4787-0

  • Online ISBN: 978-1-4614-4788-7

  • eBook Packages: Behavioral Science

Publish with us

Policies and ethics

Search

Navigation