Glutamate and GABA in adults with autism; an in vivo study using magnetic resonance spectroscopy. (360G-Wellcome-091300_Z_10_Z)

The biological associates of ASD are poorly understood. There is, nevertheless, increasing indirect evidence from genetic [3-12], neuroanatomical [5, 13-15], and peripheral metabolic studies [16-19] that abnormalities in glutamate and GABA may be central. Until recently, however, we could not directly measure their brain concentration in vivo. Proton Magnetic Resonance Spectroscopy (1H MRS) now allows that. We reported pilot evidence that ASD adults have a significant elevation in the combined signal of glutamate and glutamine (Glx) in the amygdala-hippocampal region [20]. However, the field strength of the MRI scanner, and technical methods, then available did not allow clear distinction between the two metabolites or assessment of GABA. Recent developments in 1H MRS now make it possible. Hence we wish to extend our work using new 1H MRS techniques at higher magnetic field strengths. We will measure, for the first time, both glutamate and GABA in brain regions freque ntly implicated in ASD (the amygdala-hippocampal complex and cerebellum), and an occipital control region. We will test the hypothesis that medication na ve young people with ASD have a significant elevation in glutamate and GABA concentration compared to controls; and the subsidiary hypothesis that regional increases in these neurochemicals are associated with clinical symptoms.