Elevated 3T proton MRS glutamate levels associated with poor Continuous Performance Test (CPT-0X) scores and genetic risk for schizophrenia

Purdon, Scot E.; Valiakalayil, Agitha; Hanstock, Christopher C.; Seres, Peter; Tibbo, Philip G.

doi:10.1016/j.schres.2007.11.028

Cited by 62 publications

(39 citation statements)

References 25 publications

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“…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). Concordantly, analyzing the medial-PFC in HR subjects, EP and schizophrenia patients, Natsubori et al (2014) revealed significant decrease in Glu metabolites only in the schizophrenia group.…”

Section: Discussionsupporting

confidence: 62%

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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Section: Discussionsupporting

confidence: 62%

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

et al. 2017

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“…Similarly, creatine levels reflect both phosphocreatine and unphosphorylated creatine, and some metabolites are harder to measure separately than others (for example, Glu and Gln). At 3-T field strength, however, Glu and Gln, have been reliably separated by numerous investigators, including Purdon et al, 60 Harris et al, 93 Shibuya-Tayoshi et al, 94 Shulman et al, 95 Gallinat et al, 96 and Schubert et al 97 Given the high quality of our mesial prefrontal cortical Glu spectra (S/N = 7-9, FHWM = 0.05-0.068 p.p.m., CRLB = 14-16.4%), we believe the results accurately reflect Glu levels. As many amino acids, including Glu, are also involved in intermediary metabolism and protein synthesis, it is difficult to separate their biochemical role from their transmitter role.…”

Section: Discussionmentioning

confidence: 99%

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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“…To minimize variability, some researchers have sought to reduce heterogeneity in the clinical presentation of schizophrenia samples by classifying patients based on Crow, 1985;Strauss et al, 1974), specific symptom clusters (e.g., passivity delusions or auditory hallucinations; Blakemore et al, 2000), deficit versus non-deficit forms of the illness (e.g., Carpenter et al, 1988;McGlashan, 1998), or clinically homogeneous schizophrenia groups that account for genetic variation (e.g., cognitive endophenotypes; Turetsky et al, 2007;see Fioravanti et al, 2005 andReichenberg andHarvey, 2007 for reviews). Some studies have found differentiable patterns of cognitive performance in schizophrenic samples classified using some of these approaches (e.g., Brazo et al, 2002;Brazo et al, 2005;Liu et al, 2007;Purdon et al, 2008). While such approaches help identify trends in mean cognitive performance in subgroups of patients with schizophrenia, it is still unclear how they reduce the variability in cognitive test performance in this population.…”

Section: Introductionmentioning

confidence: 99%

Stability of cognitive impairment in chronic schizophrenia over brief and intermediate re‐test intervals

Pietrzak

Snyder

Jackson

et al. 2008

Human Psychopharmacology

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Elevated 3T proton MRS glutamate levels associated with poor Continuous Performance Test (CPT-0X) scores and genetic risk for schizophrenia

Cited by 62 publications

References 25 publications

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

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

Proton MRS in twin pairs discordant for schizophrenia

Stability of cognitive impairment in chronic schizophrenia over brief and intermediate re‐test intervals

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