7T Proton Magnetic Resonance Spectroscopy of Gamma-Aminobutyric Acid, Glutamate, and Glutamine Reveals Altered Concentrations in Patients With Schizophrenia and Healthy Siblings

Thakkar, Katharine N.; Rösler, Lara; Wijnen, Jannie P.; Boer, Vincent O.; Klomp, Dennis W. J.; Cahn, Wiepke; Kahn, René S.; Neggers, Sebastiaan F. W.

doi:10.1016/j.biopsych.2016.04.007

Cited by 83 publications

(85 citation statements)

References 81 publications

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“…Our hypothesis is further supported by the finding that for the sub-group of patients defined a priori as having residual schizophrenia, the effect size was larger, and indeed was largely responsible for the difference in scores between patients and controls. This finding is consistent with prior evidence indicating increased glutamatergic transmission early in the illness but diminished glutamate in older or more functionally impaired cases [29][30][31][32][33][34][35][36][37]. All three metabolites measured in the ACC were significantly lower in the group with residual schizophrenia than in the control group.…”

Section: Discussionsupporting

confidence: 82%

“…These studies provide some evidence of elevated glutamine levels in ACC/mPFC, especially in the early phase of illness. Overall, these studies indicate that glutamate may be unchanged or reduced, especially in more chronic cases, depending on the persistence of symptoms or other factors associated with long-term illness [29][30][31][32][33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

“…However, glutamate and glutamine each participate in several other distinct cell processes and hence may not be closely coupled [28]. MRS studies of glutamate and glutamine concentrations in schizophrenia have been inconsistent, with some studies reporting an increase, others reporting a decrease or no abnormality ( [29][30][31][32][33][34][35], for reviews see [36,37]). 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].…”

Section: Introductionmentioning

confidence: 99%

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Glutathione and glutamate in schizophrenia: a 7T MRS study

et al. 2018

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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.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glutathione and glutamate in schizophrenia: a 7T MRS study

et al. 2018

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“…Most importantly, the degree of LRTC and the precision in audio-tactile perception were partial mediators of the link between Glx and schizophrenia proneness, in the presence of a direct negative link between Glx and SPQ in our sample. Our results are thus also broadly consistent with prior evidence showing that altered glutamatergic neurotransmission, due to either increased 99 or reduced 100 glutamatergic metabolites, and altered activity of glutamate receptors 101 are associated with subclinical and clinical manifestations of psychosis. In addition, they suggest one possible mechanism that may specifically mediate this hypothesized link in the context of perceptual disturbance.…”

Section: Discussionsupporting

confidence: 81%

A Neural “Tuning Curve” for Multisensory Experience and Cognitive-Perceptual Schizotypy

Ferri

Nikolova

Perrucci

et al. 2017

Schizophrenia Bulletin

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Our coherent perception of external events is enabled by the integration of inputs from different senses occurring within a range of temporal offsets known as the temporal binding window (TBW), which varies from person to person. A relatively wide TBW may increase the likelihood that stimuli originating from different environmental events are erroneously integrated and abnormally large TBW has been found in psychiatric disorders characterized by unusual perceptual experiences. Despite strong evidence of inter-individual differences in TBW, both within clinical and nonclinical populations, the neurobiological underpinnings of this variability remain unclear. We adopted an integrated strategy linking TBW to temporal dynamics in functional magnetic resonance imaging (fMRI)-resting-state activity and cortical excitation/inhibition (E/I) balance. E/I balance was indexed by glutamate/Gamma-AminoButyric Acid (GABA) concentrations and common variation in glutamate and GABA genes in a healthy sample. Stronger resting-state longrange temporal correlations, indicated by larger power law exponent (PLE), in the auditory cortex, robustly predicted narrower audio-tactile TBW, which was in turn associated with lower cognitive-perceptual schizotypy. Furthermore, PLE was highest and TBW narrowest for individuals with intermediate levels of E/I balance, with shifts towards either extreme resulting in reduced multisensory temporal precision and increased schizotypy, effectively forming a neural "tuning curve" for multisensory experience and schizophrenia risk. Our findings shed light on the neurobiological underpinnings of multisensory integration and its potentially clinically relevant inter-individual variability.

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“…In recent years, functional MRI, perfusion MRI, diffusion tensor imaging (DTI), MRI spectroscopy, single-photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic encephalography have been widely used. 2,[14][15][16][17] The first MRI study on SAD was conducted by Pott et al 18 who reported no significant differences in the cerebral, caudate, putamen, and thalamic volumes in the patient and control groups of 20 individuals. On the other hand, Milham et al 19 used MRI voxel-based morphometry and demonstrated a decrease only in the left amygdala in nine of the 17 patients diagnosed with SAD.…”

Section: Discussionmentioning

confidence: 99%