Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

Abstract

Objective: Both Tourette's disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) have been related to abnormalities in glutamatergic neurochemistry in the fronto-striatal circuitry. TD and ADHD often co-occur and the neural underpinnings of this co-occurrence have been insufficiently investigated in prior studies.

Method: We used proton magnetic resonance spectroscopy (1H-MRS) in children between 8 and 12 years of age (TD n = 15, ADHD n = 39, TD + ADHD n = 29, and healthy controls n = 53) as an in vivo method of evaluating glutamate concentrations in the fronto-striatal circuit. Spectra were collected on a 3 Tesla Siemens scanner from two voxels in each participant: the anterior cingulate cortex (ACC) and the left dorsal striatum. LC-model was used to process spectra and generate glutamate concentrations in institutional units. A one-way analysis of variance was performed to determine significant effects of diagnostic group on glutamate concentrations.

Results: We did not find any group differences in glutamate concentrations in either the ACC (F₍₃₁₃₂₎ = 0.97, p = 0.41) or striatum (F₍₃₁₂₁₎ = 0.59, p = 0.62). Furthermore, variation in glutamate concentration in these regions was unrelated to age, sex, medication use, IQ, tic, or ADHD severity. Obsessive-compulsive (OC) symptoms were positively correlated with ACC glutamate concentration within the participants with TD (rho = 0.35, p_uncorrected = 0.02).

Conclusion: We found no evidence for glutamatergic neuropathology in TD or ADHD within the fronto-striatal circuits. However, the correlation of OC-symptoms with ACC glutamate concentrations suggests that altered glutamatergic transmission is involved in OC-symptoms within TD, but this needs further investigation.

Keywords: ADHD; Fronto-striatal circuit; Glutamate; MRS; Tourette syndrome.

Fig. 1

Location of the two voxels are shown on a T1-weighted anatomical image for the pregenual ACC including an example spectrum (top) and the left dorsal striatum including an example spectrum (bottom). Peaks corresponding to individual metabolites are highlighted. The thin black line represents the frequency-domain data, the red line is the LCModel fit. In the top panel the residuals are plotted (the data minus the fit). Cho, choline; Cre, creatine; Gln, glutamine; Glu, glutamate; Glx, Glu + Gln; mI, myo-inositol; NAA, N-acetylaspartate.

Fig. 2

Boxplots of glutamate concentrations per group in the ACC and striatum. No group differences in glutamate levels were seen. ADHD, attention-deficit/hyperactivity disorder; HC, healthy controls; i.u., institutional units; TD, Tourette's disorder; TD + ADHD, Tourette's disorder and comorbid attention-deficit/hyperactivity disorder.

Fig. 3

Correlation of ACC glutamate concentration with obsessive–compulsive symptoms (CY-BOCS total score) in participants with TD. ACC, anterior cingulate cortex; CY-BOCS, Children's Yale-Brown Obsessive Compulsive Scale; i.u., institutional units; TD, Tourette's disorder. The solid line and its shaded area denote the linear regression fit line and its 95% confidence interval.