Effects of riluzole on excitation-inhibition imbalance and functional connectivity in 22q11.2 deletion syndrome: a multimodal 7-Tesla MRI study.

22q11.2 deletion syndrome (22q11.2DS) is associated with several psychiatric pathologies, including psychosis and cognitive impairment. This may be partially attributable to genetically-mediated imbalance of glutamatergic (excitatory) to GABAergic (inhibitory) neurotransmission, which could also modulate functional connectivity. Modifying excitation-inhibition balance with the antiglutamatergic drug riluzole may therefore treat psychotic and cognitive symptoms. Eight individuals with 22q11.2DS experiencing cognitive and/or psychotic symptoms received eight-weeks of placebo followed by eight-weeks of riluzole. After each intervention period, 7 Tesla magnetic resonance spectroscopy of the dorsal anterior cingulate cortex (dACC) and resting-state functional connectivity measurements were acquired, alongside cognitive and psychiatric assessment. Riluzole did not significantly alter dACC glutamate or GABA concentrations, or functional connectivity of the dACC. However, the ratio of dACC glutamate to GABA was significantly correlated with dACC - left insula functional connectivity post-riluzole (ρ = -0.96, p = 0.033, FDR corrected). Participants with higher glutamate after placebo had greater trend-level reductions in glutamate (ρ = -0.71, p = 0.06) post-riluzole. Exploratory analyses suggested potential associations between MRI and clinical measurements. Despite a lack of significant findings on primary outcome measures, this study demonstrates the feasibility of a multimodal MRI approach in clinical trials within 22q11.2DS, and identifies potential avenues for further research.