Proton Magnetic Resonance Spectroscopy (1H MRS) in Schizophrenia: Investigation of the Right and Left Hippocampus, Thalamus, and Prefrontal Cortex

Delamillieure, Pascal; Constans, Jean-Marc; Fernández, J.L. Navarro; Brazo, P.; Bénali, Karim; Courthéoux, P.; Thibaut, Florence; Petit, Michel; Dollfus, Sonia

doi:10.1093/oxfordjournals.schbul.a006942

Cited by 51 publications

(21 citation statements)

References 57 publications

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“…This result is incompatible with a neurodegenerative hypothesis of 17 schizophrenia [28] but may indicate either decreased glial content or more dysfunctional glia in more severe disease [30].…”

Section: Discussioncontrasting

confidence: 63%

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Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

et al. 2014

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Background: Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS). Methods: Schizophrenia patients with (AH; n=12) and without hallucinations (NH; n=8) and healthy controls (HC; n=11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyrus were defined anatomically. Results: The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4±6.1 mm (range: 2.7-36.1 mm) for Broca's area and 16.8±6.2 mm (range:4.5-26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p = 0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p = 0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p = 0.03) and negative (p = 0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p = 0.008). Conclusion: This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci. Highlights

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Section: Discussioncontrasting

confidence: 63%

“…With respect to schizophrenia, an increase in mI concentrations compared to healthy controls would be compatible with the neurodegenerative hypothesis but has not been found as of yet [28]. Instead, most studies have shown that mI levels in schizophrenia are largely unaltered (as reviewed in [29]).…”

Section: Introductionmentioning

confidence: 95%

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

et al. 2014

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“…The regionally lower levels of GCPII expression we demonstrated in schizophrenia are not likely due to atrophy within the frontal or mesial temporal lobe since schizophrenia is not likely a neurodegenerative disease -the composition of neurons and glia remain largely intact (Lim et al, 1998), particularly in dorsolateral PFC (Molina et al, 2006), although there is a demonstrable decrease in hippocampal volume that is diagnostically specific (Harrison, 2004). However, some MRS-based studies posit that regionally low NAA levels may indeed be due to neuron loss or at least dysfunction (Delamillieure et al, 2002).…”

Section: 1mentioning

confidence: 69%

Dysregulation of glutamate carboxypeptidase II in psychiatric disease

Guilarte

Hammoud

McGlothan

et al. 2008

Schizophrenia Research

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Experimental evidence is beginning to converge on an important role for dysregulation of glutamate carboxypeptidase II (GCPII) in schizophrenia. The goal of this study was to determine GCPII levels in postmortem brain specimens of patients with schizophrenia, bipolar disorder or unipolar depression and age-matched control subjects. We used, a high-affinity radioligand for GCPII, to probe for GCPII expression in prefrontal cortex (PFC) and mesial temporal lobe, two brain regions implicated in the pathophysiology of schizophrenia. We found that GCPII levels measured by [ 125 I]DCIT quantitative autoradiography were significantly lower in the PFC and entorhinal cortex in patients with schizophrenia compared to age-matched controls. Patients with bipolar disorder also expressed significantly lower GCPII levels in PFC than controls. The decrease in [ 125 I]DCIT binding in schizophrenia and bipolar disorder remained significant after adjusting for drug abuse. A significant difference in GCPII levels were also observed between schizophrenia relative to bipolar disorder and depressed subjects in the hippocampus-stratum lucidum and between schizophrenia and bipolar in the CA2 region of the hippocampus with bipolar and depressed subjects expressing higher levels of GCPII than subjects with schizophrenia. These differences in hippocampal GCPII levels may implicate differences in the etiologies of these mental disorders. In summary, this study demonstrates a regional dysregulation of GCPII expression in the brain of patients with schizophrenia and other

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“…40 There is evidence suggesting that alterations in brain mI may be associated with psychiatric disorders such as bipolar disorder and schizophrenia, 90 but most spectroscopy studies have reported normal mI concentrations in several brain regions in schizophrenic patients. 18,28,91,92 Hence, the verdict on mI abnormalities in schizophrenia awaits further study.…”

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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Proton Magnetic Resonance Spectroscopy (1H MRS) in Schizophrenia: Investigation of the Right and Left Hippocampus, Thalamus, and Prefrontal Cortex

Cited by 51 publications

References 57 publications

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

Dysregulation of glutamate carboxypeptidase II in psychiatric disease

Proton MRS in twin pairs discordant for schizophrenia

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