Key result
Single-dose riluzole numerically decreases anterior cingulate cortex glutamate and GABA in 22q11.2 deletion syndrome.
Why the study?
22q11.2 deletion syndrome is associated with impaired cognition and hypothesized disruption of glutamate/GABA balance, which may be a target for pharmacological treatment.
Does a single dose of 50 mg riluzole alter glutamate and GABA metabolite concentrations in patients with 22q11.2 deletion syndrome and healthy controls?
RCT (n=37)
Double-blind
crossover
Does a single dose of 50 mg riluzole alter glutamate and GABA metabolite concentrations in patients with 22q11.2 deletion syndrome and healthy controls?
A single dose of riluzole can modulate glutamate and GABA concentrations in the anterior cingulate cortex in both 22q11.2 deletion syndrome patients and healthy controls.
Answers are grounded in this paper and cite their sources.
Single-dose riluzole yields numerical ACC metabolite reductions; extends mechanistic data in 22q11.2DS but leaves clinical utility open.
Aims: 22q11.2 deletion syndrome (22q11.2DS) is associated with impaired cognitive functioning. Glutamatergic pathways have been linked with cognition and are hypothesized to be disrupted in 22q11.2DS patients, possibly ‘shifting’ the excitatory (glutamate)/inhibitory (GABA) balance. Hence, the glutamate/GABA balance may constitute a target for pharmacological treatment. We aimed to examine alterations of glutamate/GABA metabolites in 22q11.2DS in vivo using riluzole, a compound with glutamate/GABA-modulating action, as pharmacological challenge. Methods: Seventeen 22q11.2DS patients and 20 matched healthy controls were enrolled in this randomized double-blind placebo-controlled crossover study. Glutamate and glutamine concentrations in the anterior cingulate cortex (ACC) and striatum, as well as ACC GABA concentrations were obtained after placebo and after a single dose of 50 mg riluzole using 7-Tesla magnetic resonance spectroscopy (MRS). Within the 22q11.2DS group, the relationship between metabolite concentrations and cognition was examined. Results: No group differences were found in ACC and striatal metabolite concentrations following placebo. Riluzole numerically decreased ACC ( η 2 = 0.094) but not striatal glutamate concentrations as well as ACC GABA concentrations ( η 2 = 0.176) in all subjects. In both regions, riluzole did not alter glutamine concentration. No interaction effects were found. Although not significant after Bonferroni correction, ACC glutamate concentrations were inversely correlated with cognitive functions in 22q11.2DS patients. Discussion: We did not demonstrate altered ACC and striatal metabolite concentrations in 22q11.2DS. Nevertheless, these results suggest that glutamate and GABA can be modulated with a single dose of riluzole. Possibly, riluzole may have memory-enhancing effects in 22q11.2DS. Future studies should examine the long-term effects of riluzole on cognition.
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Vingerhoets et al. (2020) conducted an RCT in 22q11.2 deletion syndrome (n=37). Riluzole vs. Placebo was evaluated on Glutamate and glutamine concentrations in the anterior cingulate cortex (ACC) and striatum, and ACC GABA concentrations. A single 50 mg dose of riluzole numerically decreased anterior cingulate cortex glutamate (η2=0.094) and GABA (η2=0.176) concentrations in both 22q11.2 deletion syndrome patients and healthy controls.
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