Regional Decoupling of N-acetyl-aspartate and Glutamate in Schizophrenia

Kraguljac, Nina; Reid, Meredith A.; White, David M.; Hollander, J.; Lahti, Adrienne C.

doi:10.1038/npp.2012.126

Cited by 79 publications

(67 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[26][27][28][29][30] However, the quality of the spectral fits is not always clear in these reports (except for [27][28][29] ) and the samples were small (9 to 30 for the schizophrenia groups 6 ). More recent studies reported increases, [31][32][33][34][35] reductions 25,[36][37][38] and no differences 39 in Glx or glutamate. Two 33,34 of the 5 recent studies documenting elevations involved more ventral regions.…”

Section: Discussionmentioning

confidence: 99%

Glutamatergic and Neuronal Dysfunction in Gray and White Matter: A Spectroscopic Imaging Study in a Large Schizophrenia Sample

Bustillo

Jones

Chen

et al. 2016

SCHBUL

View full text Add to dashboard Cite

Glutamine plus glutamate (Glx), as well as N-acetylaspartate compounds (NAAc, N-acetylaspartate plus N-acetyl-aspartyl-glutamate), a marker of neuronal viability, can be quantified with proton magnetic resonance spectroscopy ( 1 H-MRS). We used 1 H-MRS imaging to assess Glx and NAAc, as well as totalcholine (glycerophospho-choline plus phospho-choline), myo-inositol and total-creatine (creatine plus phosphocreatine) from an axial supraventricular slab of gray matter (GM, medial-frontal and medial-parietal) and white matter (WM, bilateral-frontal and bilateralparietal) voxels. Schizophrenia subjects (N = 104) and healthy controls (N = 97) with a broad age range (16 to 65) were studied. In schizophrenia, Glx was increased in GM (P < .001) and WM (P = .01), regardless of age. However, with greater age, NAAc increased in GM (P < .001) but decreased in WM (P < .001) in schizophrenia. In patients, total creatine decreased with age in WM (P < .001). Finally, overall cognitive score correlated positively with WM neurometabolites in controls but negatively in the schizophrenia group (NAAc, P < .001; and creatine [only younger], P < .001). We speculate the results support an ongoing process of increased glutamate metabolism in schizophrenia. Later in the illness, disease progression is suggested by increased cortical compaction without neuronal loss (elevated NAAc) and reduced axonal integrity (lower NAAc). Furthermore, this process is associated with fundamentally altered relationships between neurometabolite concentrations and cognitive function in schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 99%

Glutamatergic and Neuronal Dysfunction in Gray and White Matter: A Spectroscopic Imaging Study in a Large Schizophrenia Sample

Bustillo

Jones

Chen

et al. 2016

SCHBUL

View full text Add to dashboard Cite

show abstract

“…One metaanalysis found that glutamate is reduced and glutamine is increased in the ACC in patients with schizophrenia, and both decrease more markedly with age in patients [38]. A more recent meta-analysis found higher medial-frontal Glx (glutamate + glutamine) levels in high-risk subjects [39]. Three recent studies used ultra-high field strength (7T) MRS, as its greater spectral resolution and signal-to-noise ratio help to distinguish between these two metabolites.…”

Section: Introductionmentioning

confidence: 99%

Glutathione and glutamate in schizophrenia: a 7T MRS study

et al. 2018

View full text Add to dashboard Cite

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate, and/or glutamine in the cerebral cortex, consistent with a post-inflammatory response, and that this reduction would be most marked in patients with "residual schizophrenia", in whom an early stage with positive psychotic symptoms has progressed to a late stage characterized by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender, and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton magnetic resonance spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal components analysis (PCA) produced three clear components: an ACC glutathione-glutamate component; an insula-visual glutathione-glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione-glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excitotoxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness.

show abstract

“…Since previous studies have reported correlations between glutamate and NAA in certain brain areas (Colla et al, 2009;Waddell et al, 2011;Kraguljac et al, 2012) and in due consideration that glutamate and NAA are linked through the Krebs cycle (tricarboxylic acid cycle) (Moffett et al, 2007), the altered NAA concentrations in the present study are more comprehensible. Owing to this connectivity of the two compounds, some authors hypothesized that the abundant supply of NAA in neurons provides a reservoir for glutamate (Clark et al, 2006).…”

Section: Discussionmentioning

confidence: 62%