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.
Highlights
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome with childhood onset that affects ~ 5% of children and 2.5% of adults.[1]
An exploratory analysis of symptom dimensions in stimulant-naive ADHD participants revealed that the concentration of glutamate and glutamine (Glx) in the basal ganglia voxel was negatively correlated with total Barkley Scale Inattention score (n = 24, r = − 0.610, P = 0.004), with lower Glx concentrations associated with more severe symptoms of inattention (Figure 4)
We report significantly reduced concentrations of glutamate/ glutamine (Glx) in the caudate/putamen of adults with ADHD, compared with matched healthy controls as measured using [1H] MRS
Summary
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome with childhood onset that affects ~ 5% of children and 2.5% of adults.[1]. There is substantial evidence that individuals with ADHD have abnormalities in brain anatomy and function,[4] and perhaps especially in dopamine neurotransmission[5,6] within the prefrontal cortex (PFC) and the basal ganglia—areas known to be involved in both attention and the regulation of behaviour. In terms of clinical subtypes, these, 22 symptoms of ADHD: the caudate/striatum is responsible for the regulation of attention,[22,23] whereas the DLPFC is a key part of the executive control network in the brain.[24,25]. We selected the third area, the medial parietal cortex, as a ‘control’ region, as the structure and neurochemistry of this area have not previously been linked to ADHD This was included as we wished to investigate whether any abnormalities seen in these disease-linked areas reflected specific local changes, or more widespread differences in metabolite levels. Pre-assessment questionnaires included the Barkley Scales[27], which provides both self- and informant assessment for (a) adulthood and (b) childhood symptoms
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