Glutamate and functional connectivity - support for the excitatory-inhibitory imbalance hypothesis in autism spectrum disorders. (30th July 2021)

• Record Type: Journal Article
• Authors: Siegel-Ramsay, Jennifer E.; Romaniuk, Liana; Whalley, Heather C.; Roberts, Neil; Branigan, Holly; Stanfield, Andrew C.; Lawrie, Stephen M.; Dauvermann, Maria R.
• Is Part Of: Psychiatry research. Volume 313(2021)
• Publication Date: 2021-07-30
• Subjects: Anterior cingulate cortex -- Proton Magnetic Resonance Spectroscopy -- Magnetic Resonance Imaging -- Resting-state functional connectivity -- Glutamate -- Glutamate+Glutamine; Psychiatry -- Periodicals; Brain -- Imaging -- Periodicals; Psychiatry -- Periodicals; Diagnostic Imaging -- Periodicals; Psychiatrie -- Périodiques; Cerveau -- Imagerie pour le diagnostic -- Périodiques; 616.890754
• DOI: 10.1016/j.pscychresns.2021.111302
• Languages: English
• ISSNs: 0925-4927

Abstract

Highlights: Patients showed a negative relationship between Glx and functional connectivity. Controls displayed a positive relationship between Glx and functional connectivity. Findings partly support the excitatory-inhibitory imbalance theory in ASD. Abstract: It has been proposed that the Glutamate (Glu) system is implicated in autism spectrum disorders (ASD) via an imbalance between excitatory and inhibitory brain circuits, which impacts on brain function. Here, we investigated the excitatory-inhibitory imbalance theory by measuring Glu-concentrations and the relationship with resting-state function. Nineteen adult males with ASD and 19 age and sex-matched healthy controls (HC) (23 - 58 years) underwent Proton Magnetic Resonance Spectroscopy of the dorsal anterior cingulate cortex (dACC) and resting-state functional Magnetic Resonance Imaging (fMRI). Glu and Glx concentrations were compared between groups. Seed-based functional connectivity was analyzed with a priori seeds of the right and left dACC. Finally, metabolite concentrations were related to functional connectivity coefficients and compared between both groups. Individuals with ASD showed significantly negative associations between increased Glx concentrations and reduced functional connectivity between the dACC and insular, limbic and parietal regions. In contrast, HC displayed a positive relationship between the same metabolite and connectivity measures. We provided new evidence to support the excitatory-inhibitory imbalance theory, where excitatory Glx concentrations were related to functional dysconnectivity in ASD. Future research is needed to investigate large-scale functional networks in association with both excitatory and inhibitory metabolites in subpopulations of ASD.