Relationship among Glutamine, γ-Aminobutyric Acid, and Social Cognition in Autism Spectrum Disorders.
OBJECTIVE
An imbalance of excitatory and inhibitory neurotransmission in autism spectrum disorder (ASD) has been proposed. We compared glutamate (Glu), glutamine (Gln), and γ-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.
1 Child and Adolescent NeuroDevelopment Initiative, University of Massachusetts Medical School , Worcester, Massachusetts.
David M
DM
Cochran
Elif M
EM
Sikoglu
Steven M
SM
Hodge
Richard A E
RA
Edden
Ann
A
Foley
David N
DN
Kennedy
Constance M
CM
Moore
Jean A
JA
Frazier
D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000378:metabolism / Q000523:psychology*; D003071:Cognition; D003404:Creatinine / Q000032:analysis; D005973:Glutamine / Q000032:analysis*; D006179:Gyrus Cinguli / Q000737:chemistry*; D006801:Humans; D007360:Intelligence; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
D005973:Glutamine; D005680:gamma-Aminobutyric Acid; D003404:Creatinine