Abstract
Background: Resting-state functional dysconnectivity is commonly reported in schizophrenia (SCZ) but the underlying neurobiological mechanism remains unknown. Altered excitatory and inhibitory function may play a role but has never been examined. This project investigated the relationship between glutamate and GABA levels assessed with proton MRS and functional connectivity in SCZ.
Methods: Resting state fMRI and MRS were acquired from 58 SCZ patients and 62 healthy controls (HC). FMRI data were processed to obtain seed-based correlation maps by extracting the BOLD time series from the anterior cingulate spectroscopic voxel and calculating the temporal correlation between this reference waveform and time courses of all other brain voxels. Spectra were processed using LCModel and GANNET to quantify glutamate and GABA levels, respectively.
Results: Reduced functional connectivity in SCZ were found between the ACC/medial PFC and the left thalamus and right cuneus, and the middle frontal gyrus; and bilateral anterior cingulate, parahippocampal gyrus, superior temporal gyrus, medial frontal gyrus, lingual gyrus, and postcentral gyrus. In the HC, positive correlations between functional connectivity and glutamate were found between the ACC/medial PFC and right inferior frontal gyrus and bilateral superior temporal gyrus; and a negative correlation between GABA and functional connection between the ACC/medial PFC and left posterior cingulate. These correlations were not statistically significant in SCZ. Interaction analyses revealedD × GABA interaction in the right ACC/medial PFC, right inferior parietal lobule, and right precuneus; and Diagnosis × Glutamate × GABA interaction was found in the left anterior cingulate. No Diagnosis × Glutamate interaction was found.
Conclusion: The present investigation is one of the first studies to examine links between functional dysconnectivity and glutamate and GABA levels in SCZ. Results indicate that glutamate and GABA play an important role in the functional connectivity modulation in the healthy brain. Absence of glutamate and GABA correlations in areas where SCZ showed significantly reduced functional connectivity suggest that this chemical–functional relationship is disrupted in schizophrenia.