Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder

S Bollmann¹, C Ghisleni², S-S Poil³, E Martin⁴, J Ball⁵, D Eich-Höchli⁶, R A E Edden⁷, P Klaver⁸, L Michels⁹, D Brandeis¹⁰, R L O'Gorman¹¹

Affiliations

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

PMID: 26101852
PMCID: PMC4490289
DOI: 10.1038/tp.2015.79

Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder

S Bollmann et al. Transl Psychiatry. 2015.

. 2015 Jun 23;5(6):e589.

doi: 10.1038/tp.2015.79.

Authors

S Bollmann¹, C Ghisleni², S-S Poil³, E Martin⁴, J Ball⁵, D Eich-Höchli⁶, R A E Edden⁷, P Klaver⁸, L Michels⁹, D Brandeis¹⁰, R L O'Gorman¹¹

Affiliations

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

PMID: 26101852
PMCID: PMC4490289
DOI: 10.1038/tp.2015.79

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.

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Figures

**Figure 1**
Left subcortical and left frontal voxel positions and representative spectra. The edited spectral fits and the position of the left subcortical and the left frontal voxel in a representative adult subject.

**Figure 2**
GABA+, Glu and Gln levels in the left subcortical and in the left frontal voxel GABA+/H₂O (top row), Glu/H₂O (middle row) and Gln/H₂O (bottom row) ratios from ADHD children, control children, ADHD adults and control adults in the subcortical voxel (left column) and in the left frontal voxel (right column). ADHD, attention-deficit/hyperactivity disorder; Gln, glutamine; Glu, glutamate.

See this image and copyright information in PMC

References

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Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder

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Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder

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