Relationship among Glutamine, gamma-Aminobutyric Acid, and Social Cognition in Autism Spectrum Disorders
Intellectual and Developmental Disabilities Research Center; Department of Psychiatry, Child and Adolescent NeuroDevelopment Initiative, Center for Comparative NeuroImaging
Chemicals and Drugs | Cognitive Neuroscience | Medicinal Chemistry and Pharmaceutics | Mental Disorders | Neuroscience and Neurobiology | Neurosciences | Pediatrics | Psychiatry | Psychiatry and Psychology
OBJECTIVE: An imbalance of excitatory and inhibitory neurotransmission in autism spectrum disorder (ASD) has been proposed. We compared glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) of 13 males with ASD and 14 typically developing (TD) males (ages 13-17), and correlated these levels with intelligence quotient (IQ) and measures of social cognition.
METHODS: Social cognition was evaluated by administration of the Social Responsiveness Scale (SRS) and the Reading the Mind in the Eyes Test (RMET). We acquired proton magnetic resonance spectroscopy ((1)H-MRS) data from the bilateral ACC using the single voxel point resolved spectroscopy sequence (PRESS) to quantify Glu and Gln, and Mescher-Garwood point-resolved spectroscopy sequence (MEGA-PRESS) to quantify GABA levels referenced to creatine (Cr).
RESULTS: There were higher Gln levels (p=0.04), and lower GABA/Cre levels (p=0.09) in the ASD group than in the TD group. There was no difference in Glu levels between groups. Gln was negatively correlated with RMET score (rho=-0.62, p=0.001) and IQ (rho=-0.56, p=0.003), and positively correlated with SRS scores (rho=0.53, p=0.007). GABA/Cre levels were positively correlated with RMET score (rho=0.34, p=0.09) and IQ (rho=0.36, p=0.07), and negatively correlated with SRS score (rho=-0.34, p=0.09).
CONCLUSIONS: These data suggest an imbalance between glutamatergic neurotransmission and GABA-ergic neurotransmission in ASD. Higher Gln levels and lower GABA/Cre levels were associated with lower IQ and greater impairments in social cognition across groups.
DOI of Published Version
Cochran DM, Sikoglu EM, Hodge SM, Edden RA, Foley A, Kennedy DN, Moore CM, Frazier JA. Relationship among Glutamine, γ-Aminobutyric Acid, and Social Cognition in Autism Spectrum Disorders. J Child Adolesc Psychopharmacol. 2015 May;25(4):314-22. doi: 10.1089/cap.2014.0112. Epub 2015 Apr 28. PubMed PMID: 25919578; PubMed Central PMCID: PMC4442578. Link to article on publisher's site
Journal of child and adolescent psychopharmacology
Cochran, David E.; Sikoglu, Elif M.; Hodge, Steven M.; Edden, Richard A.E.; Foley, Ann; Kennedy, David N.; Moore, Constance M.; and Frazier, Jean A., "Relationship among Glutamine, gamma-Aminobutyric Acid, and Social Cognition in Autism Spectrum Disorders" (2015). Intellectual and Developmental Disabilities Research Center Publications and Presentations. 45.