Association between increased anterior cingulate glutamate and psychotic-like symptoms, but not autistic traits

Abstract

BackgroundDespite many differences, autism spectrum disorder and schizophrenia spectrum disorder share environmental risk factors, genetic predispositions as well as neuronal abnormalities, and show similar cognitive deficits in working memory, perspective taking, or response inhibition. These alterations are already present in subclinical traits of these disorders. The literature proposes that alterations in the inhibitory GABAergic and excitatory glutamatergic system could explain underlying neuronal commonalities and differences.MethodsUsing magnetic resonance spectroscopy (1H-MRS), we therefore investigated the associations between glutamate concentrations in the anterior cingulate cortex (ACC), the left and right putamen, and left and right dorsolateral prefrontal cortex (DLPFC) autistic traits and psychotic-like experiences in 53 healthy individuals (28 women).ResultsApplying linear regressions and moderations analyses, we found that ACC glutamate, but none of the other concentrations, predicted positive-like symptoms. None of the other clinical scores was associated with altered levels of glutamate. We furthermore found that high levels of ACC glutamate are predictive of psychotic symptoms when glutamate concentrations in the right putamen were reduced, and that high levels of ACC glutamate are predictive of psychotic symptoms when disorganized traits were increased.ConclusionThese results indicated that an imbalance in the glutamatergic neurotransmitter system involving cortical and subcortical regions may contribute to development of psychotic-like experiences, especially positive-like symptoms. These findings may ultimately facilitate early detection of individuals transitioning into an acute episode of psychosis.

The impact of spectral basis set composition on estimated levels of cingulate glutamate and its associations with different personality traits

“…One study reported higher levels (28), whereas others found reductions (29–31) or no significant differences (32,33) in first-episode psychosis or schizophrenic patients in the ACC. The same irregularity can be found for subjects at risk for psychosis, in the ACC higher (4,11,34–36) and lower (10) glutamate levels, or even no significant results (37–39) have been described. Besides the differences between patient groups, even of the same disease stage (e.g., due to medication status), exact voxel placement, and acquisition with different scanner hardware; one problem, adding heterogeneity to the results, could be the choice of the components of a basis set.…”

“…Due to the varying TE in our 1 H-MRS data between and within the individual voxels, we utilized MARSS in INSPECTOR version 11-2021 (40) to generate six distinct PRESS basis sets for each TE (36, 37, 38, 39, 40, 41), employing a bandwidth of 2000Hz and 1024pts in each simulation. Based on the literature, we selected five different exemplar basis set compositions for illustration.…”