RDoC “in Practice” – Cross-Disorder Analyses of ADHD, OCD, ASD and Tourette

ADHD, OCD, ASD and Tourette Disorder are early-onset neurodevelopmental disorders with both phenotypic and biological overlap. Phenotypically, they share more or less of the cross-disorder traits compulsivity and impulsivity, whereas biologically they share alterations of the fronto-striatal circuits. This talk will present findings of the TACTICS programme (EU FP7 No 278948) that was designed to examine more closely common and unique biological underpinnings of these disorders. Our review of prior studies suggested (1) an increase in Glx (combination of Glu, glutamine and GABA) in the striatum across ADHD, OCD and ASD, and (2) an increased Glx signal in the anterior cingulate cortex in paediatric ASD and ADHD but a lower Glx signal in adult ASD and ADHD. In the TACTICS samples, we found increased glutamate both in children with ASD and OCD compared with controls, but no differences between the two disorders. Dimensional analyses revealed a positive correlation between compulsive behavior (measured with the Repetitive Behavior Scale) and ACC glutamate. 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. We also investigated the relation between dorsal striatal volume and N-acetyl-aspartate (NAA) and glutamate levels. NAA levels were lower in subjects with ASD compared with controls and were associated with striatal volume. Glutamate levels were also associated with striatal volume in ASD. No group differences were found for striatal volume or shape between OCD, ASD and controls neither between Tourette disorder, ADHD, and controls.

References:

• Naaijen J, Lythgoe DJ, Amiri H, Buitelaar JK, Glennon JC. Fronto-striatal glutamatergic compounds in compulsive and impulsive syndromes: a review of magnetic resonance spectroscopy studies. Neurosci Biobehav Rev. 2015 May;52:74-88
• Naaijen J, Zwiers MP, Amiri H, Williams SC, Durston S, Oranje B, Brandeis D, Boecker-Schlier R, Ruf M, Wolf I, Banaschewski T, Glennon JC, Franke B, Buitelaar JK, Lythgoe DJ. Fronto-Striatal Glutamate in Autism Spectrum Disorder and Obsessive Compulsive Disorder. Neuropsychopharmacology. 2017 Nov;42(12):2466-2467.
• Naaijen J, Forde NJ, Lythgoe DJ, Akkermans SE, Openneer TJ, Dietrich A, Zwiers MP, Hoekstra PJ, Buitelaar JK. Fronto-striatal glutamate in children with Tourette`s disorder and attention-deficit/hyperactivity disorder. Neuroimage Clin. 2016 Nov 16;13:16-23.