Skip to main content
Log in

Analysis of brain metabolism by proton magnetic resonance spectroscopy (1H-MRS) in attention-deficit/hyperactivity disorder suggests a generalized differential ontogenic pattern from controls

  • Original Article
  • Published:
ADHD Attention Deficit and Hyperactivity Disorders

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder of childhood. Preliminary studies with proton magnetic resonance spectroscopy (1H-MRS) of the brain have reported differences in brain metabolite concentration-to-Cr ratios between individuals with ADHD and unaffected controls in several frontal brain regions including anterior cingulate cortex. Using multivoxel 1H-MRS, we compared 14 individuals affected with ADHD to 20 individuals without ADHD from the same genetic isolate. After controlling by sex, age, and multiple testing, we found significant differences at the right posterior cingulate of the Glx/Cr ratio density distribution function between ADHD cases and controls (P < 0.05). Furthermore, we found several interactions of metabolite concentration-to-Cr ratio, age, and ADHD status: Ins/Cr and Glx/Cr ratios at the left posterior cingulate, and NAA/Cr at the splenius, right posterior cingulate, and at the left posterior cingulate. We also found a differential metabolite ratio interaction between ADHD cases and controls for Ins/Cr and NAA/Cr at the right striatum. These results show that: (1) NAA/Cr, Glx/Cr, and Ins/Cr ratios, as reported in other studies, exhibit significant differences between ADHD cases and controls; (2) differences of these metabolite ratios between ADHD cases and controls evolve in specific and recognizable patterns throughout age, a finding that replicates previous results obtained by structural MRI, where is demonstrated that brain ontogeny follows a different program in ADHD cases and controls; (3) Ins/Cr and NAA/Cr ratios, at the right striatum, interact in a differential way between ADHD cases and controls. As a whole, these results replicate previous 1H-MRS findings and add new intriguing differential metabolic and ontogeny patterns between ADHD cases and controls that warrant further pursue.

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

  • Acosta MT, Castellanos FX, Bolton KL, Balog JZ, Eagen P, Nee L, Jones J, Palacio L, Sarampote C, Russell HF, Berg K, Arcos-Burgos M, Muenke M (2008) Latent class subtyping of attention-deficit/hyperactivity disorder and comorbid conditions. J Am Acad Child Adolesc Psychiatry 47(7):797–807. doi:10.1097/CHI.0b013e318173f70b

    Article  PubMed  Google Scholar 

  • Arcos-Burgos M, Muenke M (2002) Genetics of population isolates. Clin Genet 61(4):233–247

    Article  PubMed  CAS  Google Scholar 

  • Arcos-Burgos M, Castellanos FX, Lopera F, Pineda D, Palacio JD, Garcia M, Henao GC, Palacio LG, Berg K, Bailey-Wilson JE, Muenke M (2002) Attention-deficit/hyperactivity disorder (ADHD): feasibility of linkage analysis in a genetic isolate using extended and multigenerational pedigrees. Clin Genet 61(5):335–343

    Article  PubMed  CAS  Google Scholar 

  • Arcos-Burgos M, Castellanos FX, Pineda D, Lopera F, Palacio JD, Palacio LG, Rapoport JL, Berg K, Bailey-Wilson JE, Muenke M (2004) Attention-deficit/hyperactivity disorder in a population isolate: linkage to loci at 4q13.2, 5q33.3, 11q22, and 17p11. Am J Hum Genet 75(6):998–1014. doi:10.1086/426154

    Article  PubMed  CAS  Google Scholar 

  • Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc: Ser B (Methodol) 57(1):289–300

    Google Scholar 

  • Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I (2001) Controlling the false discovery rate in behavior genetics research. Behav Brain Res 125(1–2):279–284

    Article  PubMed  CAS  Google Scholar 

  • Biederman J, Faraone SV (2005) Attention-deficit hyperactivity disorder. Lancet 366(9481):237–248. doi:10.1016/S0140-6736(05)66915-2

    Article  PubMed  Google Scholar 

  • Castillo M, Smith JK, Kwock L (2000) Correlation of myo-inositol levels and grading of cerebral astrocytomas. AJNR Am J Neuroradiol 21(9):1645–1649

    PubMed  CAS  Google Scholar 

  • Ellison-Wright I, Ellison-Wright Z, Bullmore E (2008) Structural brain change in attention deficit hyperactivity disorder identified by meta-analysis. BMC Psychiatry 8:51. doi:10.1186/1471-244X-8-51

    Article  PubMed  Google Scholar 

  • Faraone SV, Biederman J, Mennin D, Gershon J, Tsuang MT (1996) A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome. J Am Acad Child Adolesc Psychiatry 35(11):1449–1459. doi:10.1097/00004583-199611000-00013

    Article  PubMed  CAS  Google Scholar 

  • Hesslinger B, Thiel T, Tebartz van Elst L, Hennig J, Ebert D (2001) Attention-deficit disorder in adults with or without hyperactivity: where is the difference? A study in humans using short echo (1)H-magnetic resonance spectroscopy. Neurosci Lett 304(1–2):117–119

    Article  PubMed  CAS  Google Scholar 

  • Kadota T, Horinouchi T, Kuroda C (2001) Development and aging of the cerebrum: assessment with proton MR spectroscopy. AJNR Am J Neuroradiol 22(1):128–135

    PubMed  CAS  Google Scholar 

  • Krain AL, Castellanos FX (2006) Brain development and ADHD. Clin Psychol Rev 26(4):433–444. doi:10.1016/j.cpr.2006.01.005

    Article  PubMed  Google Scholar 

  • Lopera F, Palacio LG, Jimenez I, Villegas P, Puerta IC, Pineda D, Jimenez M, Arcos-Burgos M (1999) Discrimination between genetic factors in attention deficit. Rev Neurol 28(7):660–664

    PubMed  CAS  Google Scholar 

  • MacMaster FP, Carrey N, Sparkes S, Kusumakar V (2003) Proton spectroscopy in medication-free pediatric attention-deficit/hyperactivity disorder. Biol Psychiatry 53(2):184–187

    Article  PubMed  Google Scholar 

  • Moore CM, Biederman J, Wozniak J, Mick E, Aleardi M, Wardrop M, Dougherty M, Harpold T, Hammerness P, Randall E, Renshaw PF (2006) Differences in brain chemistry in children and adolescents with attention deficit hyperactivity disorder with and without comorbid bipolar disorder: a proton magnetic resonance spectroscopy study. Am J Psychiatry 163(2):316–318. doi:10.1176/appi.ajp.163.2.316

    Article  PubMed  Google Scholar 

  • Palacio JD, Castellanos FX, Pineda DA, Lopera F, Arcos-Burgos M, Quiroz YT, Henao GC, Puerta IC, Ramirez DL, Rapoport JL, Bailey-Wilson J, Berg K, Muenke M (2004) Attention-deficit/hyperactivity disorder and comorbidities in 18 Paisa Colombian multigenerational families. J Am Acad Child Adolesc Psychiatry 43(12):1506–1515. doi:10.1097/01.chi.0000142279.79805.dc

    Article  PubMed  Google Scholar 

  • Pelham WE, Foster EM, Robb JA (2007) The economic impact of attention-deficit/hyperactivity disorder in children and adolescents. J Pediatr Psychol 32(6):711–727. doi:10.1093/jpepsy/jsm022

    Article  PubMed  Google Scholar 

  • Perlov E, Philipsen A, Hesslinger B, Buechert M, Ahrendts J, Feige B, Bubl E, Hennig J, Ebert D, Tebartz van Elst L (2007) Reduced cingulate glutamate/glutamine-to-creatine ratios in adult patients with attention deficit/hyperactivity disorder—a magnet resonance spectroscopy study. J Psychiatr Res 41(11):934–941. doi:10.1016/j.jpsychires.2006.12.007

    Article  PubMed  CAS  Google Scholar 

  • Perlov E, Philipsen A, Matthies S, Drieling T, Maier S, Bubl E, Hesslinger B, Buechert M, Henning J, Ebert D, Tebartz Van Elst L (2009) Spectroscopic findings in attention-deficit/hyperactivity disorder: review and meta-analysis. World J Biol Psychiatry 10(4 Pt 2):355–365. doi:10.1080/15622970802176032

    Article  PubMed  Google Scholar 

  • Pineda DA, Palacio LG, Puerta IC, Merchan V, Arango CP, Galvis AY, Gomez M, Aguirre DC, Lopera F, Arcos-Burgos M (2007) Environmental influences that affect attention deficit/hyperactivity disorder: study of a genetic isolate. Eur Child Adolesc Psychiatry 16(5):337–346. doi:10.1007/s00787-007-0605-4

    Article  PubMed  Google Scholar 

  • Pineda DA, Lopera F, Puerta IC, Trujillo-Orrego N, Aguirre-Acevedo DC, Hincapie-Henao L, Arango CP, Acosta MT, Holzinger SI, Palacio JD, Pineda-Alvarez DE, Velez JI, Martinez AF, Lewis JE, Muenke M, Arcos-Burgos M (2011) Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate. Atten Defic Hyperact Disord 3(3):291–299. doi:10.1007/s12402-011-0061-3

    Article  PubMed  Google Scholar 

  • Proal E, Reiss PT, Klein RG, Mannuzza S, Gotimer K, Ramos-Olazagasti MA, Lerch JP, He Y, Zijdenbos A, Kelly C, Milham MP, Castellanos FX (2011) Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood. Arch Gen Psychiatry 68(11):1122–1134. doi:10.1001/archgenpsychiatry.2011.117

    Article  PubMed  Google Scholar 

  • Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 14(4):260–264

    Article  PubMed  CAS  Google Scholar 

  • R Development Core Team (2011) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0. http://www.R-project.org/

  • Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP, Greenstein D, Clasen L, Evans A, Giedd J, Rapoport JL (2007) Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci USA 104(49):19649–19654. doi:10.1073/pnas.0707741104

    Article  PubMed  CAS  Google Scholar 

  • Smigielska-Kuzia J, Sobaniec W (2007) Brain metabolic profile obtained by proton magnetic resonance spectroscopy HMRS in children with Down syndrome. Adv Med Sci 52(Suppl 1):183–187

    PubMed  Google Scholar 

  • Sun L, Jin Z, Zang YF, Zeng YW, Liu G, Li Y, Seidman LJ, Faraone SV, Wang YF (2005) Differences between attention-deficit disorder with and without hyperactivity: a 1H-magnetic resonance spectroscopy study. Brain Dev 27(5):340–344. doi:10.1016/j.braindev.2004.09.004

    Article  PubMed  Google Scholar 

  • Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA, Volkow N, Taylor E, Casey BJ, Castellanos FX, Wadhwa PD (2007) Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev 17(1):39–59. doi:10.1007/s11065-007-9019-9

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to extend their deepest gratitude to all the patients and families from Antioquia, Colombia, who took part in our research on ADHD. This research was supported in part by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, United States of America.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maximilian Muenke.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 87 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arcos-Burgos, M., Londoño, A.C., Pineda, D.A. et al. Analysis of brain metabolism by proton magnetic resonance spectroscopy (1H-MRS) in attention-deficit/hyperactivity disorder suggests a generalized differential ontogenic pattern from controls. ADHD Atten Def Hyp Disord 4, 205–212 (2012). https://doi.org/10.1007/s12402-012-0088-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12402-012-0088-0

Keywords

Navigation