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


Bollmann, Steffen; Ghisleni, Carmen; Poil, Simon-Shlomo; Martin, Ernst; Ball, J; Eich-Höchli, D; Edden, R A E; Klaver, Peter; Michels, Lars; Brandeis, Daniel; O'Gorman, Ruth L (2015). Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder. Translational Psychiatry, 5(6):e589.

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.

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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3 citations in Web of Science®
4 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > University Hospital Zurich > Clinic for Neuroradiology
04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:June 2015
Deposited On:23 Jul 2015 08:37
Last Modified:05 Apr 2016 19:18
Publisher:Nature Publishing Group
ISSN:2158-3188
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/tp.2015.79
PubMed ID:26101852

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