3-T Proton MRS Investigation of Glutamate and Glutamine  in Adolescents at High Genetic Risk for Schizophrenia

Tibbo, Philip G.; Hanstock, Chris; Valiakalayil, Agitha; Allen, Peter S.

doi:10.1176/appi.ajp.161.6.1116

Cited by 142 publications

(104 citation statements)

References 13 publications

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“…A few years later, similar results in first-episode schizophrenic patients were reported in the prefrontal cortex and the hippocampus (48). Furthermore, a study of nonpsychotic adolescents at genetic risk for schizophrenia found significantly increased Glx in the right medial frontal lobe (49). Glutamine levels in the anterior cingulate and thalamus reduce as disease progresses and this reduction correlated with progressive gray Figure 4.…”

Section: Proton Mrs Studies Of Glutamatesupporting

confidence: 53%

MR spectroscopy in schizophrenia

Port

Agarwal

2011

Magnetic Resonance Imaging

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The purpose of this study is to review the MR spectroscopic literature regarding schizophrenia. However, as there are over 250 primary MRS articles and dozens of MRS review articles on the subject already, this study will take a different approach. First, the clinical features of schizophrenia will be described. The background neuroanatomy and biochemistry relevant to schizophrenia will be reviewed, as many readers of this journal are unlikely to be familiar with these fields. A current model of the abnormal neural circuitry in schizophrenia will be presented, and predictions extrapolated about relevant metabolite changes over time. Finally, the existing MRS literature will be reviewed in the context of our existing anatomical and chemical knowledge, and future MRS research directions will be elaborated. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.

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Section: Proton Mrs Studies Of Glutamatesupporting

confidence: 53%

MR spectroscopy in schizophrenia

Port

Agarwal

2011

Magnetic Resonance Imaging

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“…Starting from this prodromal phase, progressive changes in brain volume, including the PFC, and disturbances in Glu-neurotransmission (Marsman et al 2013) may occur. Tibbo et al (2004) found significantly higher levels of Glu in the right medial frontal lobe of HR compared to controls, although other studies failed to replicate these findings. Purdon et al (2008) finding the absence of differences in Glu metabolites levels between HR and HC in the same brain region, as was for Yoo et al (2009).…”

Section: Discussionmentioning

confidence: 87%

Cannabis use in early psychosis is associated with reduced glutamate levels in the prefrontal cortex

et al. 2017

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Rationale Recent studies have shown that cannabis may disrupt glutamate (Glu) signaling depressing Glu tone in frequent users. Current evidence have also consistently reported lower Glu-levels in various brain regions, particularly in the medial prefrontal cortex (mPFC) of chronic schizophrenia patients, while findings in early psychosis (EP) are not conclusive. Since cannabis may alter Glu synaptic plasticity and its use is a known risk factor for psychosis, studies focusing on Glu signaling in EP with or without a concomitant cannabis-usage seem crucial.Objective We investigate the effect of cannabis use on prefrontal Glu-levels in EP users vs. both EP non-users and healthy controls (HC). Methods Magnetic resonance spectroscopy was used to measure [Glu mPFC ] of 35 EP subjects (18 of whom were cannabis users) and 33 HC. For correlative analysis, neuropsychological performances were scored by the MATRICS-consensus cognitive battery. Results [Glu mPFC ] was lower in EP users comparing to both HC and EP non-users (p < 0.001 and p = 0.01, respectively), while no differences were observed between EP non-users and HC. A greater [Glu mPFC ]-decline with age was observed in EP users (r = −.46; p = 0.04), but not in EP non-users or HC. Among neuropsychological outcomes, working memory was the only domain that differentiates patients depending on their cannabis use, with users having poorer performances. Conclusions Cannabis use is associated with reduced prefrontal [Glu mPFC ] and with a stronger Glu-levels decline with age. Glutamatergic abnormalities might influence the cognitive impairment observed in users and have some relevance for the progression of the disease.

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“…Although not yet consistently supported by MRS studies, which have shown increased levels of Glu in the mesPFC, 49 and reduced levels in anterior cingulate gyrus 46 and thalamus 50 of schizophrenia subjects compared with controls, based on the hypoglutamatergic hypothesis of schizophrenia, [51][52][53] we predicted a reduction in Glu in patients compared with controls.…”

Section: Introductionmentioning

confidence: 79%

Proton MRS in twin pairs discordant for schizophrenia

et al. 2008

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Proton magnetic resonance spectroscopy ( 1 H MRS) neurometabolite abnormalities have been detected widely in subjects with and at risk for schizophrenia. We hypothesized that such abnormalities would be present both in patients with schizophrenia and in their unaffected twin siblings. We acquired magnetic resonance spectra (TR/TE = 3000/30 ms) at voxels in the mesial prefrontal gray matter, left prefrontal white matter and left hippocampus in 14 twin pairs discordant for schizophrenia (2 monozygotic, 12 dizygotic), 13 healthy twin pairs (4 monozygotic, 9 dizygotic) and 1 additional unaffected co-twin of a schizophrenia proband. In the mesial prefrontal gray matter voxel, N-acetylaspartate (NAA), creatine þ phosphocreatine (Cr), glycerophosphocholine þ phosphocholine (Cho) and myo-inositol (mI) did not differ significantly between patients with schizophrenia, their unaffected co-twins or healthy controls. However, glutamate (Glu) was significantly lower in patients with schizophrenia (31%, percent difference) and unaffected co-twins (21%) than in healthy controls (collapsed across twin pairs). In the left hippocampus voxel, levels of NAA (23%), Cr (22%) and Cho (36%) were higher in schizophrenia patients compared with controls. Hippocampal NAA (25%), Cr (22%) and Cho (37%) were also significantly higher in patients than in their unaffected co-twins. Region-to-region differences in metabolite levels were also notable within all three diagnosis groups. These findings suggest that 1 H MRS neurometabolite abnormalities are present not only in patients with schizophrenia, but also in their unaffected co-twins. Thus, reduced mesial prefrontal cortical Glu and elevated hippocampal NAA, Cr and Cho may represent trait markers of schizophrenia risk and, when exacerbated, state markers of schizophrenia itself.

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3-T Proton MRS Investigation of Glutamate and Glutamine in Adolescents at High Genetic Risk for Schizophrenia

Abstract: The finding of glutamate/glutamine abnormalities in a group of subjects at high genetic risk for schizophrenia lends support for both the glutamate dysfunction and neurodevelopmental hypotheses for schizophrenia.

Cited by 142 publications

References 13 publications

MR spectroscopy in schizophrenia

MR spectroscopy in schizophrenia

Cannabis use in early psychosis is associated with reduced glutamate levels in the prefrontal cortex

Proton MRS in twin pairs discordant for schizophrenia

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