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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

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.
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fig2: 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.

Mentions: Comparing GABA+/H2O levels in the subcortical voxel in children and adults with and without ADHD revealed a significant age group by diagnostic group interaction (F(1,85)=5.11, P=0.026, ω2=0.04; Figure 2), which remained significant after FDR correction for multiple comparisons. Post hoc t-tests demonstrated that ADHD adults had higher GABA+/H2O values (M=1.98, s.d.=0.20) compared with controls (M=1.87, s.d.=0.17). This difference was significant, t(52)=2.03, P=0.048, d=0.56. ADHD children showed no significant differences in GABA+/H2O values in the subcortical voxel (M=1.85, s.d.=0.17) compared with controls (M=1.91, s.d.=0.13), t(33)=−1.25, P>0.1, d=0.43.


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)

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

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

fig2: 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.
Mentions: Comparing GABA+/H2O levels in the subcortical voxel in children and adults with and without ADHD revealed a significant age group by diagnostic group interaction (F(1,85)=5.11, P=0.026, ω2=0.04; Figure 2), which remained significant after FDR correction for multiple comparisons. Post hoc t-tests demonstrated that ADHD adults had higher GABA+/H2O values (M=1.98, s.d.=0.20) compared with controls (M=1.87, s.d.=0.17). This difference was significant, t(52)=2.03, P=0.048, d=0.56. ADHD children showed no significant differences in GABA+/H2O values in the subcortical voxel (M=1.85, s.d.=0.17) compared with controls (M=1.91, s.d.=0.13), t(33)=−1.25, P>0.1, d=0.43.

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