TY - JOUR
T1 - Developmental changes in fronto-striatal glutamate and their association with functioning during inhibitory control in autism spectrum disorder and obsessive compulsive disorder
AU - Hollestein, Viola
AU - Buitelaar, Jan K
AU - Brandeis, Daniel
AU - Banaschewski, Tobias
AU - Kaiser, Anna
AU - Hohmann, Sarah
AU - Oranje, Bob
AU - Gooskens, Bram
AU - Durston, Sarah
AU - Williams, Steven C R
AU - Lythgoe, David J
AU - Naaijen, Jilly
N1 - Funding Information:
The research leading to these results was supported by the European Community’s Seventh Framework Program (FP7/2007-2013) TACTICS under grant agreement no. 278948; the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115300 (EU-AIMS), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7- /2007 - 2013) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution; and a VENI grant of the Netherlands Organization for Scientific Research (NWO, grant number VI.Veni.194.032) awarded to J.N.
Publisher Copyright:
© 2021 The Authors
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3/10
Y1 - 2021/3/10
N2 - Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) show overlapping symptomatology and deficits in inhibitory control, which are associated with altered functioning and glutamatergic signaling in fronto-striatal circuitry. These parameters have never been examined together. The purpose of the current study was to investigate functioning during inhibitory control and its association with fronto-striatal glutamate concentrations across these disorders using a multi-center, longitudinal approach. Adolescents with ASD (n = 24), OCD (n = 15) and controls (n = 35) underwent two magnetic resonance imaging (MRI) sessions with a one-year interval. This included proton magnetic resonance spectroscopy (1H-MRS; n = 74) and functional MRI during an inhibitory control task (n = 53). We investigated 1H-MRS data and fMRI data separately as well as integrated in a multimodal analysis using linear models focusing on diagnosis and continuous measures of overlapping compulsivity symptoms. ACC glutamate was reduced over time in the ASD group compared with controls, while striatal glutamate decreased over time independent of diagnosis. Increased compulsive behavior seemed to be associated with increased striatal activity during failed inhibitory control. The integrated analyses showed differential involvement of increased striatal glutamate during failed but decreased striatal glutamate during successful inhibitory control in the OCD group compared to controls and ASD, suggesting different underlying mechanisms for OCD compared to ASD.
AB - Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) show overlapping symptomatology and deficits in inhibitory control, which are associated with altered functioning and glutamatergic signaling in fronto-striatal circuitry. These parameters have never been examined together. The purpose of the current study was to investigate functioning during inhibitory control and its association with fronto-striatal glutamate concentrations across these disorders using a multi-center, longitudinal approach. Adolescents with ASD (n = 24), OCD (n = 15) and controls (n = 35) underwent two magnetic resonance imaging (MRI) sessions with a one-year interval. This included proton magnetic resonance spectroscopy (1H-MRS; n = 74) and functional MRI during an inhibitory control task (n = 53). We investigated 1H-MRS data and fMRI data separately as well as integrated in a multimodal analysis using linear models focusing on diagnosis and continuous measures of overlapping compulsivity symptoms. ACC glutamate was reduced over time in the ASD group compared with controls, while striatal glutamate decreased over time independent of diagnosis. Increased compulsive behavior seemed to be associated with increased striatal activity during failed inhibitory control. The integrated analyses showed differential involvement of increased striatal glutamate during failed but decreased striatal glutamate during successful inhibitory control in the OCD group compared to controls and ASD, suggesting different underlying mechanisms for OCD compared to ASD.
UR - http://www.scopus.com/inward/record.url?scp=85103020376&partnerID=8YFLogxK
U2 - 10.1016/j.nicl.2021.102622
DO - 10.1016/j.nicl.2021.102622
M3 - Article
C2 - 33765540
SN - 2213-1582
VL - 30
SP - 102622
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 102622
ER -