Grey matter and social functioning correlates of glutamatergic
                        metabolite loss in schizophrenia

Aoyama, Naoko; Théberge, Jean; Drost, Dick J.; Manchanda, Rahul; Northcott, Sandra; Neufeld, Richard W. J.; Menon, Ravi S.; Rajakumar, Nagalingam; Pavlosky, William; Densmore, Maria; Schaefer, Betsy; Williamson, Peter C.

doi:10.1192/bjp.bp.110.079608

Cited by 100 publications

(133 citation statements)

References 34 publications

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“…Although not systematically evaluated, other studies with smaller samples have failed to detect abnormalities in dorsal regions. 7,35,[57][58][59] Also, several studies suggest that glutamatergic increases may be more robust in ventral brain regions 23,24,[33][34][35][60][61][62] with effect sizes larger than here reported. We are currently implementing a whole-brain 1 H-MRSI sequence.…”

Section: Discussioncontrasting

confidence: 51%

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

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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.

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Section: Discussioncontrasting

confidence: 51%

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

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“…An additional subtle cognitive decline during the late prodrome is likely -i.e. prior to the first episode when early disease processes may precipitate neurodegenerative changes (Harvey, 2009;Aoyama et al 2011). It should, however, be stated that such cognitive decline does not necessarily reflect a functional loss, rather it is linked to an inability to acquire new information and skills (Bedwell et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Precursors of cognitive impairments in psychotic disorders: A population-based study

Müller

Vetter

Weiser

et al. 2013

Psychiatry Research

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Cognitive deficits have been found to be more prevalent in psychotic than in other disorders. Longitudinal research has shown that these deficits were generally already existent before onset of illness and are therefore not necessarily attributable to neurodegenerative processes. This study investigated whether both low IQ and markers of premorbid cognitive dysfunction independently contribute to an increased risk for psychoses. In a cross-sectional study about 50,000 young Swiss males completed a survey of intellectual problems in childhood/adolescence and other vulnerability factors during military call-up in 2005/2006. Subsequently, military IQ assessments were carried out on the entire sample. Diagnostic assessments were conducted according to International Classification of Diseases-10th edition (ICD-10). Low, especially performance, IQ was highly associated with an increased risk for psychotic disorders after adjusting for preexisting cognitive deficits and covariates, while in other disorders this association was less marked. Furthermore, preexisting intellectual problems emerged as important risk factors for psychoses. Our results confirm the importance of low IQ as characteristic of psychoses. Although premorbid intellectual deficits are common in people who go on to develop psychosis, neurodegenerative disease processes may also precipitate further declines in fluid cognitive functions. Assessment of cognitive functioning should be taken into account in early detection of psychoses. Longitudinal research has shown that these deficits were generally already existent before onset of illness and are therefore not necessarily attributable to neurodegenerative processes. This study investigated whether both low IQ and markers of premorbid cognitive dysfunction independently contribute to an increased risk for psychoses. In a cross-sectional study about Subsequently, military IQ assessments were carried out on the entire sample. Diagnostic assessments were conducted according to ICD-10. Low, especially performance IQ was highly associated with an increased risk for psychotic disorders after adjusting for preexisting cognitive deficits and covariates; while in other disorders this association was less marked.Furthermore, preexisting intellectual problems emerged as important risk factors for psychoses.Our results confirm the importance of low IQ as characteristic of psychoses. Although premorbid intellectual deficits are common in people who go on to develop psychosis, neurodegenerative disease processes may also precipitate further declines in fluid cognitive functions. Assessment of cognitive functioning should be taken into account in early detection of psychoses.

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“…Other studies did not show a treatment effect on glutamate levels in the prefrontal cortex [32][33][34][35], although in one studies improvement of negative symptoms was related to increased Glx levels [32] and improvement on total PANSS to lower Glx levels [9]. The observed changes by antipsychotics on Glx levels may be caused by their dopaminergic effects on glutamatergic receptor activity and density and modulation of glutamate release [36].…”

Section: Researchmentioning

confidence: 99%

The Effect of Aripiprazole versus Risperidone on Prefrontal Brain Metabolite Levels and Brain Volume in Psychotic Disorders: An Exploratory Study

Liemburg¹,

Sibeijn-Kuiper²,

Knegtering³

et al. 2018

Neuropsychiatry

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ObjectiveGiven that aripiprazole acts as a partial agonist on the dopamine receptor, it may have unique effects on brain neuro-metabolism, specifically in the prefrontal cortex. In this exploratory study, we investigated the effect of aripiprazole compared to risperidone on prefrontal metabolite levels (Glx, NAA, Creatine, Choline and myo-Inositol) and changes in gray and white matter volume (GMV and WMV) in patients with a psychotic disorder. We hypothesized that patients treated with aripiprazole would show increased levels of Glx and NAA and preserved brain volumes, in contrast to risperidone. MethodsIn this randomized, single blind study, patients (n=24) treated with either risperidone or aripiprazole underwent magnetic resonance spectroscopy ( 1 H-MRS) and high-resolution anatomical scans (3T) at baseline and after 9 weeks. LC Model was used to determine the absolute spectral metabolite levels and SPM12 was to perform voxel based morphometry analyses. Both metabolite levels and brain volumes were compared between treatment groups. ResultsWe found a trend for a different effect of both antipsychotics on Glx levels, whereby risperidone reduced Glx levels compared to aripiprazole. Moreover, patients treated with aripiprazole showed a decreased GMV in the precentral gyrus, caudate and lateral frontal regions and increased WMV in the precentral gyrus and a non-significant but consistent pattern of prefrontal WM increases, in contrast to risperidone. ConclusionOur results point to possibility of different effects of aripiprazole on brain volume and metabolism compared to risperidone. Studies in larger samples are needed to shed more light on the robustness and nature of such differences.

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Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia

Abstract: Brain metabolite loss is correlated with deteriorated social functioning and grey matter losses in schizophrenia, consistent with neurodegeneration.

Cited by 100 publications

References 34 publications

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

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

Precursors of cognitive impairments in psychotic disorders: A population-based study

The Effect of Aripiprazole versus Risperidone on Prefrontal Brain Metabolite Levels and Brain Volume in Psychotic Disorders: An Exploratory Study

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