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.
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Citation: 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
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.