Skip to main content
Log in

Serum protein profiling and proteomics in autistic spectrum disorder using magnetic bead-assisted mass spectrometry

  • Original Paper
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

The pathophysiology of autistic spectrum disorder (ASD) is not fully understood and there are no diagnostic or predictive biomarkers. Proteomic profiling has been used in the past for biomarker research in several non-psychiatric and psychiatric disorders and could provide new insights, potentially presenting a useful tool for generating such biomarkers in autism. Serum protein pre-fractionation with C8-magnetic beads and protein profiling by matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-ToF-MS) were used to identify possible differences in protein profiles in patients and controls. Serum was obtained from 16 patients (aged 8–18) and age-matched controls. Three peaks in the MALDI-ToF-MS significantly differentiated the ASD sample from the control group. Sub-grouping the ASD patients into children with and without comorbid Attention Deficit and Hyperactivity Disorder, ADHD (ASD/ADHD+ patients, n = 9; ASD/ADHD− patients, n = 7), one peak distinguished the ASD/ADHD+ patients from controls and ASD/ADHD− patients. Our results suggest that altered protein levels in peripheral blood of patients with ASD might represent useful biomarkers for this devastating psychiatric disorder.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Achenbach TM, Edelbrock CS (1981) Behavioural problems and competencies reported by parents of normal and disturbed children aged four through sixteen. Monogr Soc Res Child Dev 46(1):1–82

    Article  CAS  PubMed  Google Scholar 

  2. Belmonte MK, Cook EH Jr, Anderson GM, Rubenstein JL, Greenough WT, Beckel-Mitchener A, Courchesne E, Boulanger LM, Powell SB, Levitt PR, Perry EK, Jiang YH, DeLorey TM, Tierney E (2004) Autism as a disorder of neural information processing: directions for research and targets for therapy. Mol Psychiatry 9(7):646–663

    CAS  PubMed  Google Scholar 

  3. Boelte S (2006) PF. FSK—Fragebogen zur Sozialen Kommunikation. Huber, Bern

    Google Scholar 

  4. Boelte SRD, Schmoetzer G, Poustka F (2006) ADI-R—Diagnostisches Interview fuer Autismus - Revidiert. Huber, Bern

    Google Scholar 

  5. Cheng AJ, Chen LC, Chien KY, Chen YJ, Chang JT, Wang HM, Liao CT, Chen IH (2005) Oral cancer plasma tumor marker identified with bead-based affinity-fractionated proteomic technology. Clin Chem 51(12):2236–2244

    Article  CAS  PubMed  Google Scholar 

  6. Cook EH, Leventhal BL (1996) The serotonin system in autism. Curr Opin Pediatr 8(4):348–354

    Article  CAS  PubMed  Google Scholar 

  7. Cook EH Jr, Leventhal BL, Heller W, Metz J, Wainwright M, Freedman DX (1990) Autistic children and their first-degree relatives: relationships between serotonin and norepinephrine levels and intelligence. J Neuropsychiatry Clin Neurosci 2(3):268–274

    PubMed  Google Scholar 

  8. Corbett BA, Kantor AB, Schulman H, Walker WL, Lit L, Ashwood P, Rocke DM, Sharp FR (2007) A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins. Mol Psychiatry 12(3):292–306

    CAS  PubMed  Google Scholar 

  9. Coutinho AM, Oliveira G, Morgadinho T, Fesel C, Macedo TR, Bento C, Marques C, Ataide A, Miguel T, Borges L, Vicente AM (2004) Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism. Mol Psychiatry 9(3):264–271

    Article  CAS  PubMed  Google Scholar 

  10. Croonenberghs J, Delmeire L, Verkerk R, Lin AH, Meskal A, Neels H, Van der Planken M, Scharpe S, Deboutte D, Pison G, Maes M (2000) Peripheral markers of serotonergic and noradrenergic function in post-pubertal, caucasian males with autistic disorder. Neuropsychopharmacology 22(3):275–283

    Article  CAS  PubMed  Google Scholar 

  11. D’Eufemia P, Finocchiaro R, Celli M, Viozzi L, Monteleone D, Giardini O (1995) Low serum tryptophan to large neutral amino acids ratio in idiopathic infantile autism. Biomed Pharmacother 49(6):288–292

    Article  PubMed  Google Scholar 

  12. de Noo ME, Deelder A, van der Werff M, Ozalp A, Mertens B, Tollenaar R (2006) MALDI-TOF serum protein profiling for the detection of breast cancer. Onkologie 29(11):501–506

    Article  PubMed  Google Scholar 

  13. de Noo ME, Mertens BJ, Ozalp A, Bladergroen MR, van der Werff MP, van de Velde CJ, Deelder AM, Tollenaar RA (2006) Detection of colorectal cancer using MALDI-TOF serum protein profiling. Eur J Cancer 42(8):1068–1076

    Article  PubMed  Google Scholar 

  14. Devlin B, Cook EH Jr, Coon H, Dawson G, Grigorenko EL, McMahon W, Minshew N, Pauls D, Smith M, Spence MA, Rodier PM, Stodgell C, Schellenberg GD (2005) Autism and the serotonin transporter: the long and short of it. Mol Psychiatry 10(12):1110–1116

    Article  CAS  PubMed  Google Scholar 

  15. Ebert MP, Niemeyer D, Deininger SO, Wex T, Knippig C, Hoffmann J, Sauer J, Albrecht W, Malfertheiner P, Rocken C (2006) Identification and confirmation of increased fibrinopeptide a serum protein levels in gastric cancer sera by magnet bead assisted MALDI-TOF mass spectrometry. J Proteome Res 5(9):2152–2158

    Article  CAS  PubMed  Google Scholar 

  16. Hashimoto K, Iwata Y, Nakamura K, Tsujii M, Tsuchiya KJ, Sekine Y, Suzuki K, Minabe Y, Takei N, Iyo M, Mori N (2006) Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism. Prog Neuropsychopharmacol Biol Psychiatry 30(8):1529–1531

    Article  CAS  PubMed  Google Scholar 

  17. Jyonouchi H, Sun S, Le H (2001) Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J Neuroimmunol 120(1–2):170–179

    Article  CAS  PubMed  Google Scholar 

  18. Kaufman AS, Kaufman NL (1983) K-ABC interpretive manual. American Guidance Service, Circle Pines

    Google Scholar 

  19. Kaufman AS, Kaufman NL (1983) K-ABC administration and scoring manual. American Guidance Service, Circle Pines

    Google Scholar 

  20. Kemper TL, Bauman ML (2002) Neuropathology of infantile autism. Mol Psychiatry 7(Suppl 2):S12–S13

    Article  PubMed  Google Scholar 

  21. Lake CR, Ziegler MG, Murphy DL (1977) Increased norepinephrine levels and decreased dopamine-beta-hydroxylase activity in primary autism. Arch Gen Psychiatry 34(5):553–556

    CAS  PubMed  Google Scholar 

  22. Launay JM, Bursztejn C, Ferrari P, Dreux C, Braconnier A, Zarifian E, Lancrenon S, Fermanian J (1987) Catecholamines metabolism in infantile autism: a controlled study of 22 autistic children. J Autism Dev Disord 17(3):333–347

    Article  CAS  PubMed  Google Scholar 

  23. Leventhal BL, Cook EH Jr, Morford M, Ravitz A, Freedman DX (1990) Relationships of whole blood serotonin and plasma norepinephrine within families. J Autism Dev Disord 20(4):499–511

    Article  CAS  PubMed  Google Scholar 

  24. Lord C, Rutter M, Goode S, Hemsbergen J, Jordan H, Mawhood L, Schopler E (1989) Autism diagnostic observation schedule: a standardized observation of communicative and social behavior. J Autism Dev Disord 19(2):185–212

    Article  CAS  PubMed  Google Scholar 

  25. Lord C, Rutter M, Le Couteur A (1994) Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 24(5):659–685

    Article  CAS  PubMed  Google Scholar 

  26. Malik G, Ward MD, Gupta SK, Trosset MW, Grizzle WE, Adam BL, Diaz JI, Semmes OJ (2005) Serum levels of an isoform of apolipoprotein A-II as a potential marker for prostate cancer. Clin Cancer Res 11(3):1073–1085

    CAS  PubMed  Google Scholar 

  27. McBride PA, Anderson GM, Hertzig ME, Snow ME, Thompson SM, Khait VD, Shapiro T, Cohen DJ (1998) Effects of diagnosis, race, and puberty on platelet serotonin levels in autism and mental retardation. J Am Acad Child Adolesc Psychiatry 37(7):767–776

    Article  CAS  PubMed  Google Scholar 

  28. Miyazaki K, Narita N, Sakuta R, Miyahara T, Naruse H, Okado N, Narita M (2004) Serum neurotrophin concentrations in autism and mental retardation: a pilot study. Brain Dev 26(5):292–295

    Article  PubMed  Google Scholar 

  29. Molloy CA, Morrow AL, Meinzen-Derr J, Schleifer K, Dienger K, Manning-Courtney P, Altaye M, Wills-Karp M (2006) Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol 172(1–2):198–205

    Article  CAS  PubMed  Google Scholar 

  30. Muhle R, Trentacoste SV, Rapin I (2004) The genetics of autism. Pediatrics 113(5):e472–e486

    Article  PubMed  Google Scholar 

  31. Naffah-Mazzacoratti MG, Rosenberg R, Fernandes MJ, Draque CM, Silvestrini W, Calderazzo L, Cavalheiro EA (1993) Serum serotonin levels of normal and autistic children. Braz J Med Biol Res 26(3):309–317

    CAS  PubMed  Google Scholar 

  32. Nelson KB, Grether JK, Croen LA, Dambrosia JM, Dickens BF, Jelliffe LL, Hansen RL, Phillips TM (2001) Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Ann Neurol 49(5):597–606

    Article  CAS  PubMed  Google Scholar 

  33. Nelson PG, Kuddo T, Song EY, Dambrosia JM, Kohler S, Satyanarayana G, Vandunk C, Grether JK, Nelson KB (2006) Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory and concentrations in neonatal blood of children with autism or Down syndrome. Int J Dev Neurosci 24(1):73–80

    Article  CAS  PubMed  Google Scholar 

  34. Okada K, Hashimoto K, Iwata Y, Nakamura K, Tsujii M, Tsuchiya KJ, Sekine Y, Suda S, Suzuki K, Sugihara G, Matsuzaki H, Sugiyama T, Kawai M, Minabe Y, Takei N, Mori N (2007) Decreased serum levels of transforming growth factor-beta1 in patients with autism. Prog Neuropsychopharmacol Biol Psychiatry 31(1):187–190

    Article  CAS  PubMed  Google Scholar 

  35. Polleux F, Lauder JM (2004) Toward a developmental neurobiology of autism. Ment Retard Dev Disabil Res Rev 10(4):303–317

    Article  PubMed  Google Scholar 

  36. Ruehl D, Feineis-Matthews S, Poustka F (2004) ADOS—Diagnostische Beobachtungsskala fuer Autistische Stoerungen. Huber, Bern

    Google Scholar 

  37. Rutter M, Bailey A, Berument SK, Le Couteur A, Lord C, Pickles A (2003) Social communication questionnaire (SCQ). Western Psychological Services, Los Angeles

    Google Scholar 

  38. Schmitz C, Rezaie P (2007) The neuropathology of autism: where do we stand? Neuropathol Appl Neurobiol 34:4–11

    PubMed  Google Scholar 

  39. Singh VK, Warren RP, Odell JD, Cole P (1991) Changes of soluble interleukin-2, interleukin-2 receptor, T8 antigen, and interleukin-1 in the serum of autistic children. Clin Immunol Immunopathol 61(3):448–455

    Article  CAS  PubMed  Google Scholar 

  40. Snijders JT, Tellegen PJ, Laros JA (1989) Snijders-Oomen Nonverbal Intelligence Test, SON-R. Manual & Research Report Lisse. Swets & Zeitlinger, Amsterdam

    Google Scholar 

  41. Tewes U, Rossmann P, Schallberger U (1999) Hamburg-Wechsler-Intelligenztest für Kinder (HAWIK III). Hans Huber, Bern

    Google Scholar 

  42. Tirumalai RS, Chan KC, Prieto DA, Issaq HJ, Conrads TP, Veenstra TD (2003) Characterization of the low molecular weight human serum proteome. Mol Cell Proteomics 2(10):1096–1103

    Article  CAS  PubMed  Google Scholar 

  43. Warren RP, Singh VK (1996) Elevated serotonin levels in autism: association with the major histocompatibility complex. Neuropsychobiology 34(2):72–75

    Article  CAS  PubMed  Google Scholar 

  44. Zhang H, Kong B, Qu X, Jia L, Deng B, Yang Q (2006) Biomarker discovery for ovarian cancer using SELDI-TOF-MS. Gynecol Oncol 102(1):61–66

    Article  CAS  PubMed  Google Scholar 

  45. Zimmerman AW, Jyonouchi H, Comi AM, Connors SL, Milstien S, Varsou A, Heyes MP (2005) Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr Neurol 33(3):195–201

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by the German Research Council (DFG HU1536/1-1, HU1536/1-2).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Johannes Thome.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taurines, R., Dudley, E., Conner, A.C. et al. Serum protein profiling and proteomics in autistic spectrum disorder using magnetic bead-assisted mass spectrometry. Eur Arch Psychiatry Clin Neurosci 260, 249–255 (2010). https://doi.org/10.1007/s00406-009-0066-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-009-0066-5

Keywords

Navigation