176.4 Whole-Brain Spectroscopic Imaging of Glutamate in First-Episode Psychosis Before and After Antipsychotic Therapy

Background: Single-voxel proton magnetic resonance spectroscopy (H-MRS) studies of schizophrenia generally report increases in glutamate-related compounds (glutamine, glutamate or glutamate+glutamine -Glx) in various gray and white matter brain regions. However, the spatial specificity and persistence of glutamatergic abnormalities is not well characterized. For example, one meta-analysis in schizophrenia reported glutamatergic elevations only in basal ganglia and medial temporal lobe (Merrit, 2016). However, the largest study to date found small elevations of Glx in medial frontal cortex (Bustillo, 2016) and another study reported glutamate normalization in the caudate following antipsychotic treatment (de la Fuente, 2013). We used echo planar spectroscopic imaging (EPSI), a 3-dimensional H-MRS to examine Glx and N-acetyl-aspartate compounds (NAAc, a marker of neuronal viability), in psychotic subjects before and following treatment with antipsychotic medication. Methods: Twenty-seven patients seeking treatment for their first psychotic episode and 17 healthy subjects were studied at baseline. 19 schizophrenia/schizophreniform and 8 bipolar subjects participated. Seventeen patients were reimaged following antipsychotic treatment (4–8 weeks). We acquired EPSI at 3T with a 32-channel coil with the following parameters: TR/TE = 1551/17.6 msec; spatial array of 50 × 50 × 18, FOV of 280 × 280 × 180 mm3 (corresponding to a nominal voxel size of 5.6 × 5.6 × 10 mm3). Water suppression with frequency-selective saturation pulses and inversion-recovery nulling of lipid signal was performed with an inversion time of 198 milliseconds. Glx and NAAc were fitted with MIDAS. Results: At baseline, Glx was increased in the patient group in an area encompassing the superior temporal gyrus and the Rolandic operculum on the right hemisphere (FDR alpha = .05, a cluster of 125 2 × 2 × 2 mm voxels). No differences in NAAc survived FDR correction. There were no significant changes in Glx or NAAc in the psychotic patients following antipsychotic treatment. Conclusion: Elevations in glutamatergic metabolism are present early at the intersection of the central sulcus with the superior temporal gyrus in the right hemisphere. However, there is no evidence of neuronal damage at this stage of the illness. This is consistent with the literature showing progressive volume loss in schizophrenia. If increased glutamate contributes to structural changes, glutamate modulation may improve long-term outcome.