Altered Glutamate and Regional Cerebral Blood Flow Levels in Schizophrenia: A 1H-MRS and pCASL study

Abstract

The neurobiology of schizophrenia (SZ) may be altered in older versus younger adults with SZ, as less frequent episodes of symptom exacerbation and increased sensitivity to medications are observed in older age. The goal of this study was to examine the effect of age and diagnosis on glutamate and cerebral blood flow (rCBF) in adults with SZ and healthy controls. Young and older adults with SZ and healthy controls were recruited to participate in this study. Participants completed a neuropsychological battery and neuroimaging that included optimized magnetic resonance spectroscopy to measure anterior cingulate (AC) glutamate (Glu) and glutamine (Gln) and arterial spin labeling evaluation for rCBF. Regression analyses revealed significant effects of age with Glu, Gln, Gln/Glu, and AC white matter (WM) rCBF. Glu and WM rCBF decreased linearly with age while Gln and Gln/Glu increased linearly with age. Glu was lower in adults with SZ compared with healthy controls and in older adults versus younger adults but there was no interaction. Glu and WM rCBF were correlated with the UCSD Performance-Based Skills Assessment (UPSA) and processing speed, and the correlations were stronger in the SZ group. In the largest sample to date, lower Glu and elevated Gln/Glu levels were observed in adults with SZ and in older subjects. Contrary to expectation, these results do not show evidence of accelerated Glu aging in the anterior cingulate region in SZ compared with healthy controls.

Putative Astroglial Dysfunction in Schizophrenia: A Meta-Analysis of 1H-MRS Studies of Medial Prefrontal Myo-Inositol

“…If a single study was reported as 2 samples, the largest sample was included. In case of partial overlap, both studies were included with weighting based only on the non-overlapping sample for the smaller study ( 28 , 29 ). We also excluded studies where no information was available on voxel placement ( 30 ) or when study-specific Cramer-Rao Lower Bound (a measure of MRS signal quality and reliability) was exceeded for myo-inositol signal ( 31 ).…”

Salivary kynurenic acid response to psychological stress: inverse relationship to cortical glutamate in schizophrenia

“…Proportion of gray matter in the spectroscopic voxel did not significantly differ between patients and controls (t = 1.49, p = .14). MR spectroscopy data for 37 patients and 28 controls were included in previous reports [38,39] but none of the stress-induced KYNA data were previously reported.…”

Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine‐to‐glutamate ratio and myo‐inositol concentration in the mouse frontal cortex

“…; Wijtenburg et al . ). Moreover, meta‐analyses suggested a decline with age and disease duration in the levels of glutamate and glutamine (Schwerk et al .…”

“…Bustillo et al (2017) reported recently that, with age, N-acetylaspartate increases in cortical grey matter and decreases in white matter of schizophrenia patients (Bustillo et al 2016). Alterations have also been abundantly reported for glutamine and glutamate concentrations: increased glutamine, glutamate and/or and the ratio of glutamine-to-glutamate (Gln/Glu) have been found in early stages of the disease (Tibbo et al 2004;Hashimoto et al 2005;Bustillo et al 2009Bustillo et al , 2017de la Fuente-Sandoval et al 2011;Brandt et al 2016;Merritt et al 2016), whereas decreased levels of these amino acids have often been observed in chronic patients (Tayoshi et al 2009;Ohrmann et al, 2005;Chiappelli et al 2015;Brandt et al 2016;Wijtenburg et al 2017). Moreover, meta-analyses suggested a decline with age and disease duration in the levels of glutamate and glutamine (Schwerk et al 2014), as well as N-acetylaspartate (Brugger et al 2011).…”