Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study

There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo . However, f...

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Published inTranslational psychiatry Vol. 4; no. 3; p. e373
Main Authors Maltezos, S, Horder, J, Coghlan, S, Skirrow, C, O'Gorman, R, Lavender, T J, Mendez, M A, Mehta, M, Daly, E, Xenitidis, K, Paliokosta, E, Spain, D, Pitts, M, Asherson, P, Lythgoe, D J, Barker, G J, Murphy, D G
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Published London Nature Publishing Group UK 18.03.2014
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Abstract There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo . However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD—the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)—and one ‘control’ region—the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy controls. We found that compared with controls, adult ADHD participants had a significantly lower concentration of Glx, Cr and NAA in the basal ganglia and Cr in the DLPFC, after correction for multiple comparisons. There were no differences between stimulant-treated and treatment-naive ADHD participants. In people with untreated ADHD, lower basal ganglia Glx was significantly associated with more severe symptoms of inattention. There were no significant differences in the parietal ‘control’ region. We suggest that subcortical glutamate and glutamine have a modulatory role in ADHD adults; and that differences in glutamate–glutamine levels are not explained by use of stimulant medication.
AbstractList There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo . However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD—the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)—and one ‘control’ region—the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy controls. We found that compared with controls, adult ADHD participants had a significantly lower concentration of Glx, Cr and NAA in the basal ganglia and Cr in the DLPFC, after correction for multiple comparisons. There were no differences between stimulant-treated and treatment-naive ADHD participants. In people with untreated ADHD, lower basal ganglia Glx was significantly associated with more severe symptoms of inattention. There were no significant differences in the parietal ‘control’ region. We suggest that subcortical glutamate and glutamine have a modulatory role in ADHD adults; and that differences in glutamate–glutamine levels are not explained by use of stimulant medication.
There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo. However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD-the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)-and one 'control' region-the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy controls. We found that compared with controls, adult ADHD participants had a significantly lower concentration of Glx, Cr and NAA in the basal ganglia and Cr in the DLPFC, after correction for multiple comparisons. There were no differences between stimulant-treated and treatment-naive ADHD participants. In people with untreated ADHD, lower basal ganglia Glx was significantly associated with more severe symptoms of inattention. There were no significant differences in the parietal 'control' region. We suggest that subcortical glutamate and glutamine have a modulatory role in ADHD adults; and that differences in glutamate-glutamine levels are not explained by use of stimulant medication.
Author Horder, J
Barker, G J
Xenitidis, K
O'Gorman, R
Asherson, P
Coghlan, S
Pitts, M
Mehta, M
Maltezos, S
Daly, E
Paliokosta, E
Skirrow, C
Lavender, T J
Lythgoe, D J
Murphy, D G
Mendez, M A
Spain, D
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  surname: Horder
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  email: jamie.horder@kcl.ac.uk
  organization: Department of Forensic and Neurodevelopmental Sciences, King’s College London, Institute of Psychiatry
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  surname: Coghlan
  fullname: Coghlan, S
  organization: Department of Forensic and Neurodevelopmental Sciences, King’s College London, Institute of Psychiatry
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  givenname: C
  surname: Skirrow
  fullname: Skirrow, C
  organization: King’s College London, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry
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  givenname: R
  surname: O'Gorman
  fullname: O'Gorman, R
  organization: Department of Neuroimaging, King’s College London, Institute of Psychiatry
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  organization: Department of Neuroimaging, King’s College London, Institute of Psychiatry
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  surname: Spain
  fullname: Spain, D
  organization: Department of Forensic and Neurodevelopmental Sciences, King’s College London, Institute of Psychiatry, Autism Assessment and Behavioural Genetics Clinic, South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital
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  organization: Department of Forensic and Neurodevelopmental Sciences, King’s College London, Institute of Psychiatry, Autism Assessment and Behavioural Genetics Clinic, South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, King’s College London
BackLink https://www.ncbi.nlm.nih.gov/pubmed/24643164$$D View this record in MEDLINE/PubMed
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Issue 3
Keywords ADHD
magnetic resonance spectroscopy
basal ganglia
parietal lobe
dorsolateral prefrontal cortex
Language English
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Snippet There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder...
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SubjectTerms 631/378/1697
631/45/882
692/699/476/1311
Adult
Attention Deficit Disorder with Hyperactivity - metabolism
Basal Ganglia - metabolism
Behavioral Sciences
Biological Psychology
Glutamic Acid - metabolism
Glutamine - metabolism
Humans
Magnetic Resonance Spectroscopy - methods
Medicine
Medicine & Public Health
Neurosciences
Original
original-article
Pharmacotherapy
Prefrontal Cortex - metabolism
Psychiatry
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Title Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study
URI https://link.springer.com/article/10.1038/tp.2014.11
https://www.ncbi.nlm.nih.gov/pubmed/24643164
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