Skip to main content
SpringerLink
Log in

Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit–hyperactivity disorder (ADHD)

  • Original Contribution
  • Published:
European Child & Adolescent Psychiatry Aims and scope Submit manuscript

Abstract

It has been proposed that the neurotrophin brain-derived neurotrophic factor (BDNF) may be involved in attention deficit–hyperactivity disorder (ADHD) etiopathogenesis. Alterations in BDNF serum levels have been observed in childhood/adulthood neurodevelopmental pathologies, but no evidence is available for BDNF serum concentrations in ADHD. The study includes 45 drug-naïve ADHD children and 45 age–sex matched healthy subjects. Concentration of serum BDNF was determined by the ELISA method. BDNF serum levels in patients with ADHD were not different from those of controls (mean ± SD; ADHD: 39.33 ± 10.41 ng/ml; controls: 38.82 ± 8.29 ng/ml, t = −0.26, p = 0.80). Our findings indicate no alteration of serum BDNF levels in untreated patients with ADHD. A further stratification for cognitive, neuropsychological and psychopathological assessment in a larger sample could be useful to clarify the role of BDNF in the endophenotype characterization of ADHD.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007) The worldwide prevalence of ADHD: a systematic review and meta regression analysis. Am J Psychiatry 164:942–948

    Article  PubMed  Google Scholar 

  2. Schmidt HD, Shelton RC, Duman RS (2011) Functional biomarkers of depression: diagnosis, treatment, and pathophysiology. Neuropsychopharmacology 36:2375–2394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Scassellati C, Bonvicini C, Faraone SV, Gennarelli M (2012) Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses. J Am Acad Child Adolesc Psychiatry 51:1003–1019

    Article  PubMed  Google Scholar 

  4. Cortese S (2012) The neurobiology and genetics of attention-deficit/hyperactivity disorder (ADHD): what every clinician should know. Eur J Paediatr Neurol 16:422–433

    Article  PubMed  Google Scholar 

  5. Black IB (1999) Trophic regulation of synaptic plasticity. J Neurobiol 41:108–118

    Article  CAS  PubMed  Google Scholar 

  6. Chapleau CA, Pozzo-Miller L (2007) Activity-dependent structural plasticity of dendritic spines. In: Byrne J (ed) Concise learning and memory: the editor’s selection. Elsevier, Oxford, pp 281–305

    Google Scholar 

  7. Tyler WJ, Alonso M, Bramham CR, Pozzo-Miller LD (2002) From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem 9:224–237

    Article  PubMed Central  PubMed  Google Scholar 

  8. Vicario-Abejon C, Owens D, McKay R, Segal M (2002) Role of neurotrophins in central synapse formation and stabilization. Nat Rev Neurosci 3:965–974

    Article  CAS  PubMed  Google Scholar 

  9. Fumagalli F, Racagni G, Colombo E, Riva MA (2003) BDNF gene expression is reduced in the frontal cortex of dopamine transporter knockout mice. Mol Psychiatry 8:898–899

    Article  CAS  PubMed  Google Scholar 

  10. Chourbaji S, Hellweg R, Brandis D, Zörner B, Zacher C, Lang UE et al (2004) Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior. Brain Res Mol Brain Res 121:28–36

    Article  CAS  PubMed  Google Scholar 

  11. Rios M, Fan G, Fekete C, Kelly J, Bates B, Kuehn R et al (2001) Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol 15:1748–1757

    Article  CAS  PubMed  Google Scholar 

  12. Meredith GE, Callen S, Scheuer DA (2002) Brain-derived neurotrophic factor expression is increased in the rat amygdala, piriform cortex and hypothalamus following repeated amphetamine administration. Brain Res 949:218–227

    Article  CAS  PubMed  Google Scholar 

  13. Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15:7539–7547

    CAS  PubMed  Google Scholar 

  14. Ribasés M, Serrano M, Fernández-Alvarez E, Pahisa S, Ormazabal A, García-Cazorla A et al (2007) A homozygous tyrosine hydroxylase gene promoter mutation in a patient with dopa-responsive encephalopathy: clinical, biochemical and genetic analysis. Mol Genet Metab 92:274–277

    Article  PubMed  Google Scholar 

  15. Cho SC, Kim HW, Kim BN, Kim JW, Shin MS, Chung S et al (2010) Gender-specific association of the brain-derived neurotrophic factor gene with attention-deficit/hyperactivity disorder. Psychiatry Investig 7:285–290

    Article  PubMed Central  PubMed  Google Scholar 

  16. Cho SC, Kim JW, Kim HW, Kim BN, Shin MS, Cho DY et al (2011) Effect of ADRA2A and BDNF gene–gene interaction on the continuous performance test phenotype. Psychiatr Genet 21:132–135

    Article  PubMed  Google Scholar 

  17. Fumagalli F, Cattaneo A, Caffino L, Ibba M, Racagni G, Carboni E et al (2010) Sub-chronic exposure to atomoxetine up-regulates BDNF expression and signalling in the brain of adolescent spontaneously hypertensive rats: comparison with methylphenidate. Pharmacol Res 62:523–529

    Article  CAS  PubMed  Google Scholar 

  18. Shim SH, Hwangbo Y, Kwon YJ, Jeong HY, Lee BH, Lee HJ et al (2008) Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit–hyperactivity disorder (ADHD). Prog Neuropsychopharmacol Biol Psychiatry 32:1824–1828

    Article  CAS  PubMed  Google Scholar 

  19. Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J et al (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. J Thromb Haemost 87:728–734

    CAS  Google Scholar 

  20. Karege F, Schwald M, Cisse M (2002) Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci Lett 328:261–264

    Article  CAS  PubMed  Google Scholar 

  21. Lang UE, Hellweg R, Seifert F, Schubert F, Gallinat J (2007) Correlation between serum brain-derived neurotrophic factor level and an in vivo marker of cortical integrity. Biol Psychiatry 62:530–535

    Article  CAS  PubMed  Google Scholar 

  22. Klein AB, Williamson R, Santini MA, Clemmensen C, Ettrup A, Rios M, Knudsen GM, Aznar S (2011) Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int J Neuropsychopharmacol 14:347–353

    Article  CAS  PubMed  Google Scholar 

  23. Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A et al (2010) Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry 11:763–773

    Article  PubMed  Google Scholar 

  24. Fernandes BS, Gama CS, Maria Ceresér K, Yatham LN, Fries GR, Colpo G et al (2011) Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis. J Psychiatr Res 5:1–10

    Google Scholar 

  25. Green MJ, Matheson SL, Shepherd A, Weickert CS, Carr VJ (2011) Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis. Mol Psychiatry 16:960–972

    Article  CAS  PubMed  Google Scholar 

  26. Martinotti G, Di Iorio G, Marini S, Ricci V, De Berardis D, Di Giannantonio M (2012) Nerve growth factor and brain-derived neurotrophic factor concentrations in schizophrenia: a review. J Biol Regul Homeost Agents 26:347–356

    CAS  PubMed  Google Scholar 

  27. Nakazato M, Hashimoto K, Shimizu E, Niitsu T, Iyo M (2012) Possible involvement of brain-derived neurotrophic factor in eating disorders. IUBMB Life 64:355–361

    Article  CAS  PubMed  Google Scholar 

  28. Maina G, Rosso G, Zanardini R, Bogetto F, Gennarelli M, Bocchio-Chiavetto L (2010) Serum levels of brain-derived neurotrophic factor in drug-naïve obsessive-compulsive patients: a case-control study. J Affect Disord 122:174–178

    Article  CAS  PubMed  Google Scholar 

  29. Abdallah MW, Mortensen EL, Greaves-Lord K, Larsen N, Bonefeld-Jørgensen EC, Nørgaard-Pedersen B et al (2012) Neonatal levels of neurotrophic factors and risk of autism spectrum disorders. Acta Psychiatr Scand 5 doi: 10.1111/acps.12020

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  35. Elfving B, Plougmann PH, Wegener G (2010) Detection of brain-derived neurotrophic factor (BDNF) in rat blood and brain preparations using ELISA: pitfalls and solutions. J Neurosci Methods 187:73–77

    Article  CAS  PubMed  Google Scholar 

  36. American Psychiatry Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision. 2000

  37. Kovacs M (1992) Children’s Depression Inventory (CDI). Mental Health Systems. Retrieved from http://www.pearsonassessments.com/HAIWEB/Cultures/en-us/Productdetail.htm?Pid=015-8044-762

  38. Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127

    Article  CAS  PubMed  Google Scholar 

  39. Zhang L, Chang S, Li Z, Zhang K, Du Y, Ott J, Wang J (2012) ADHD gene: a genetic database for attention deficit hyperactivity disorder. Nucleic Acids Res 40:1003–1009

    Article  Google Scholar 

  40. D’Sa C, Dileone RJ, Anderson GM, Sinha R (2012) Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers. Alcohol 46:253–259

    Article  PubMed Central  PubMed  Google Scholar 

  41. Corominas-Roso M, Ramos-Quiroga JA, Ribases M, Sanchez-Mora C, Palomar G, Valero S, Bosch R, Casas M (2013) Decreased serum levels of brain-derived neurotrophic factor in adults with attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol 30:1–9

    Google Scholar 

  42. Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, Schuff-Werner P, Virchow JC (2005) The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 26:115–123

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by grants from the Fondazione Mariani [RF2006] and the Italian Ministry of Health [Ricerca Corrente].

Conflict of interest

The authors declare that they have no conflict of interest and have no financial interests of any kind in publishing the results of this study.

Author information

Authors and Affiliations

  1. IRCCS “Centro S. Giovanni di Dio” Fatebenefratelli, Via Pilastroni 4, 25123, Brescia, Italy

    Catia Scassellati, Roberta Zanardini, Massimo Gennarelli & Luisella Bocchio-Chiavetto

  2. Department of Childhood and Adolescent Neuropsychiatry, Spedali Civili, Brescia, Italy

    Alessandra Tiberti, Paola Effedri & Elena Filippini

  3. Childhood and Adolescent Neuropsychiatry, Spedali Riuniti, Bergamo, Italy

    Marco Pezzani & Stefano Conte

  4. Adolescent Neuropsychiatry Unit of Fatebenefratelli and Oftalmico, Milan, Italy

    Vera Valenti & Alberto Ottolini

  5. Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

    Massimo Gennarelli

Authors
  1. Catia Scassellati
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberta Zanardini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandra Tiberti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marco Pezzani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vera Valenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paola Effedri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elena Filippini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stefano Conte
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alberto Ottolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Massimo Gennarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Luisella Bocchio-Chiavetto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Catia Scassellati.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scassellati, C., Zanardini, R., Tiberti, A. et al. Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit–hyperactivity disorder (ADHD). Eur Child Adolesc Psychiatry 23, 173–177 (2014). https://doi.org/10.1007/s00787-013-0447-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00787-013-0447-1

Keywords

Search

Navigation