Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: A randomized double-blind 7-Tesla pharmacological MRS study

Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: A randomized double-blind 7-Tesla pharmacological MRS study. Vingerhoets, C., Tse, D. H., van Oudenaren, M., Hernaus, D., van Duin, E., Zinkstok, J., Ramaekers, J. G., Jansen, J. F., McAlonan, G., & van Amelsvoort, T. J Psychopharmacol, 2020. Vingerhoets, Claudia Tse, Desmond Hy van Oudenaren, Mathilde Hernaus, Dennis van Duin, Esther Zinkstok, Janneke Ramaekers, Johannes G Jansen, Jacobus Fa McAlonan, Grainne van Amelsvoort, Therese eng 2020/05/26 06:00 J Psychopharmacol. 2020 May 25:269881120922977. doi: 10.1177/0269881120922977.

Paper doi abstract bibtex

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 (eta(2) = 0.094) but not striatal glutamate concentrations as well as ACC GABA concentrations (eta(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.

@article{RN256,
   author = {Vingerhoets, C. and Tse, D. H. and van Oudenaren, M. and Hernaus, D. and van Duin, E. and Zinkstok, J. and Ramaekers, J. G. and Jansen, J. F. and McAlonan, G. and van Amelsvoort, T.},
   title = {Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: A randomized double-blind 7-Tesla pharmacological MRS study},
   journal = {J Psychopharmacol},
   pages = {269881120922977},
   note = {Vingerhoets, Claudia
Tse, Desmond Hy
van Oudenaren, Mathilde
Hernaus, Dennis
van Duin, Esther
Zinkstok, Janneke
Ramaekers, Johannes G
Jansen, Jacobus Fa
McAlonan, Grainne
van Amelsvoort, Therese
eng
2020/05/26 06:00
J Psychopharmacol. 2020 May 25:269881120922977. doi: 10.1177/0269881120922977.},
   abstract = {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 (eta(2) = 0.094) but not striatal glutamate concentrations as well as ACC GABA concentrations (eta(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.},
   keywords = {1h-mrs
22q11.2DS
Gaba
Glutmate
cognition
riluzole
voltage-gated sodium channel blocker},
   ISSN = {1461-7285 (Electronic)
0269-8811 (Linking)},
   DOI = {10.1177/0269881120922977},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/32448020
https://journals.sagepub.com/doi/pdf/10.1177/0269881120922977},
   year = {2020},
   type = {Journal Article}
}

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