25147
Elevated Levels of Glutamate in 4-6-Month-Old Infants at High Familial Risk of Autism Spectrum Disorders

Saturday, May 13, 2017: 12:00 PM-1:40 PM
Golden Gate Ballroom (Marriott Marquis Hotel)
I. Pote1,2, R. Dimitrova1,2, J. Ciarrusta1,2, E. Perry2, J. Kangas2, J. M. Allsop1, E. Hughes1, M. Fox1, D. G. Murphy2, G. M. McAlonan2 and M. A. Rutherford1, (1)Division of Imaging Sciences and Biomedical Engineering, Centre for the Developing Brain, London, United Kingdom, (2)Department of Forensic and Neurodevelopmental Sciences, and the Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
Background: There is now compelling evidence to suggest that abnormalities in excitatory and inhibitory neurotransmission may underpin 'atypical' development, including neurodevelopmental disorders such as autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy (1HMRS) provides an invaluable tool for studying brain metabolites in vivo. However, there have been no studies thus far examining the neurochemistry of ASD in early infancy; and so, we do not know if there are any neurochemical differences in infants-at-risk of developing the condition. This is an important omission, especially when considering that brain metabolite changes often precede structural abnormalities.

Objectives: In this study, 1HMRS was used to investigate whether 4-6-month-old infants at high familial risk of ASD showed differences in brain metabolite ratios, when compared to low-risk controls. Infants were considered to be at 'high-risk' if they had at least one sibling with a diagnosis of ASD, and at 'low-risk' if they had no family (first-degree relative) history of ASD.

Methods: We acquired 1HMRS at 3T from the basal ganglia of 33 infants (n=14 'high-risk' and n=19 'low-risk'), scanned between 4-6 months of age. Using a single voxel point resolved spectroscopy sequence (PRESS), set at an echo time of 55ms, glutamate measures comprised of glutamate plus glutamine (Glx) were obtained, and expressed relative to Choline (Cho) and Creatine (Cr) - i.e. Glx/Cho and Glx/Cr, respectively. Then, an analysis of covariance was used to test for group differences in these brain metabolite ratios. Infant risk group (low-risk versus high-risk) was input as a fixed factor, and the dependent variables of interest included: Glx/Cho and Glx/TCr. Infant age and sex were controlled for.

Results: Infants in the high-risk group had significantly higher levels of Glx/TCho [F(1,21)=6.04, p=0.023] and Glx/TCr [F(1,21)=4.86, p=0.039], when compared to those in the low-risk group, suggesting that absolute levels of Glx are elevated in 4-6-month-old infants at high-risk of ASD.

Conclusions: We emphasize that these results are preliminary and that data acquisition is still ongoing. Nevertheless, the findings presented in this study suggest that an imbalance in excitatory/inhibitory neurotransmission may be present in young infants genetically predisposed to developing ASD, and supports the notion that such an imbalance may partially underpin the pathophysiology of the disorder. Further proof that the glutamatergic pathway may be altered in infants-at-risk of ASD is required. However, the current findings should incentivize the ongoing search for pharmacological interventions targeting both glutamatergic and GABAergic systems.

See more of: Early Development (< 48 months)
See more of: Early Development (< 48 months)