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

Bollmann S, Ghisleni C, Poil SS, Martin E, Ball J, Eich-Höchli D, Edden RA, Klaver P, Michels L, Brandeis D, O'Gorman RL - Transl Psychiatry (2015)

Bottom Line: Co-varying for age in an analysis of covariance model resulted in a nonsignificant age by disorder interaction (P = 0.06).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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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fig1: 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.

Mentions: MR measurements were performed with a 3T GE HD.xt TwinSpeed MRI scanner (GE Healthcare, Milwaukee, WI, USA), using an eight-channel receive-only head coil. The MRI protocol included a T1-weighted spoiled gradient echo scan (TR=9.94 ms; TI=600 ms; FOV=256 mm × 192 mm; matrix=256 × 192; flip angle=8° axial plane; slice thickness=1 mm; 172 slices) for planning the positioning of the target voxels. GABA-edited MR spectra were acquired using the MEGA-PRESS method with TE=68 ms, TR=2000 ms, 320 averages (160 pairs) and an eight-step phase cycle. We acquired spectra from a 28 × 40 × 25 mm3 voxel in a subcortical region centered on the left basal ganglia (also including anterior thalamus) from all the participants. An additional 25 × 40 × 30 mm3 voxel was acquired in the left frontal lobe, centered on the dorsolateral prefrontal cortex from the adult participants (see Figure 1). The assessment of GABA with MEGA-PRESS is confounded by the co-editing of macromolecules which contribute to the edited peak at 3 p.p.m., so the GABA findings described subsequently represent GABA+ rather than pure GABA values.


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

Bollmann S, Ghisleni C, Poil SS, Martin E, Ball J, Eich-Höchli D, Edden RA, Klaver P, Michels L, Brandeis D, O'Gorman RL - Transl Psychiatry (2015)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490289&req=5

fig1: 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.
Mentions: MR measurements were performed with a 3T GE HD.xt TwinSpeed MRI scanner (GE Healthcare, Milwaukee, WI, USA), using an eight-channel receive-only head coil. The MRI protocol included a T1-weighted spoiled gradient echo scan (TR=9.94 ms; TI=600 ms; FOV=256 mm × 192 mm; matrix=256 × 192; flip angle=8° axial plane; slice thickness=1 mm; 172 slices) for planning the positioning of the target voxels. GABA-edited MR spectra were acquired using the MEGA-PRESS method with TE=68 ms, TR=2000 ms, 320 averages (160 pairs) and an eight-step phase cycle. We acquired spectra from a 28 × 40 × 25 mm3 voxel in a subcortical region centered on the left basal ganglia (also including anterior thalamus) from all the participants. An additional 25 × 40 × 30 mm3 voxel was acquired in the left frontal lobe, centered on the dorsolateral prefrontal cortex from the adult participants (see Figure 1). The assessment of GABA with MEGA-PRESS is confounded by the co-editing of macromolecules which contribute to the edited peak at 3 p.p.m., so the GABA findings described subsequently represent GABA+ rather than pure GABA values.

Bottom Line: Co-varying for age in an analysis of covariance model resulted in a nonsignificant age by disorder interaction (P = 0.06).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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus