TY - JOUR
T1 - Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers
T2 - A randomized double-blind 7-Tesla pharmacological MRS study
AU - Vingerhoets, Claudia
AU - Tse, Desmond Hy
AU - van Oudenaren, Mathilde
AU - Hernaus, Dennis
AU - van Duin, Esther
AU - Zinkstok, Janneke
AU - Ramaekers, Johannes G
AU - Jansen, Jacobus Fa
AU - McAlonan, Grainne
AU - van Amelsvoort, Therese
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by University Fund Limburg (grant no. S.2014.11).
Publisher Copyright:
© The Author(s) 2020.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8
Y1 - 2020/8
N2 - 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 (η2= 0.094) but not striatal glutamate concentrations as well as ACC GABA concentrations (η2= 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.
AB - 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 (η2= 0.094) but not striatal glutamate concentrations as well as ACC GABA concentrations (η2= 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.
KW - 22q11.2DS
KW - GABA
KW - Glutmate
KW - H-MRS
KW - cognition
KW - riluzole
KW - voltage-gated sodium channel blocker
KW - 2DS
KW - 22q11
KW - H-1-MRS
UR - http://www.scopus.com/inward/record.url?scp=85085279679&partnerID=8YFLogxK
U2 - 10.1177/0269881120922977
DO - 10.1177/0269881120922977
M3 - Article
C2 - 32448020
SN - 0269-8811
VL - 34
SP - 856
EP - 863
JO - Journal of Psychopharmacology
JF - Journal of Psychopharmacology
IS - 8
ER -