Original Article

Citation: Translational Psychiatry (2015) 5, e589; doi:10.1038/tp.2015.79
Published online 23 June 2015

Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder
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S Bollmann1,2,3,4,5, C Ghisleni1,2,3, S-S Poil1,3, E Martin1,2, J Ball6, D Eich-Höchli7, R A E Edden8,9, P Klaver1,2,3,10, L Michels11, D Brandeis2,3,6,12 and R L O'Gorman1,3,13

  1. 1Center for MR-Research, University Children’s Hospital Zurich, Zürich, Switzerland
  2. 2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zürich, Switzerland
  3. 3Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
  4. 4Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zürich, Switzerland
  5. 5Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia
  6. 6Department of Child and Adolescent Psychiatry, University of Zurich, Zürich, Switzerland
  7. 7Psychiatric University Hospital, Zürich, Switzerland
  8. 8Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  9. 9F. M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
  10. 10Department of Psychology, University of Zurich, Zürich, Switzerland
  11. 11Institute of Neuroradiology, University Hospital of Zurich, Zürich, Switzerland
  12. 12Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
  13. 13Pediatric Research Center, University Children’s Hospital Zurich, Zürich, Switzerland

Correspondence: Dr, R O'Gorman, Center for MR-Research, University Children's Hospital Zurich, Steinwiesstrasse 75, Zürich CH 8032, Switzerland. E-mail: Ruth.Tuura@kispi.uzh.ch

Received 4 August 2014; Revised 27 April 2015; Accepted 4 May 2015

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Abstract

While the neurobiological basis and developmental course of attention-deficit/hyperactivity disorder (ADHD) have not yet been fully established, an imbalance between inhibitory/excitatory neurotransmitters is thought to have an important role in the pathophysiology of ADHD. This study examined the changes in cerebral levels of GABA+, glutamate and glutamine in children and adults with ADHD using edited magnetic resonance spectroscopy. We studied 89 participants (16 children with ADHD, 19 control children, 16 adults with ADHD and 38 control adults) in a subcortical voxel (children and adults) and a frontal voxel (adults only). ADHD adults showed increased GABA+ levels relative to controls (P=0.048), while ADHD children showed no difference in GABA+ in the subcortical voxel (P>0.1), resulting in a significant age by disorder interaction (P=0.026). Co-varying for age in an analysis of covariance model resulted in a nonsignificant age by disorder interaction (P=0.06). Glutamine levels were increased in children with ADHD (P=0.041), but there was no significant difference in adults (P>0.1). Glutamate showed no difference between controls and ADHD patients but demonstrated a strong effect of age across both groups (P<0.001). In conclusion, patients with ADHD show altered levels of GABA+ in a subcortical voxel which change with development. Further, we found increased glutamine levels in children with ADHD, but this difference normalized in adults. These observed imbalances in neurotransmitter levels are associated with ADHD symptomatology and lend new insight in the developmental trajectory and pathophysiology of ADHD.