Interaction of hippocampal volume and N-acetylaspartate concentration deficits in schizophrenia: A combined MRI and 1H-MRS study

Klär, Andreas Arthur; Ballmaier, Martina; Leopold, Karolina; Häke, Ines; Schaefer, Martin; Brühl, Rüdiger; Schubert, Florian; Gallinat, Jürgen

doi:10.1016/j.neuroimage.2010.06.006

Cited by 36 publications

(21 citation statements)

References 67 publications

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“…In our study, similar to these results, NAA levels in the hippocampus were significantly decreased in the CSPs when compared to healthy controls. Consistent with previous reports, this finding was not found in the FEP group, so it suggests a progressive process in schizophrenia (14)(15)(16)48).…”

Section: Discussionsupporting

confidence: 91%

“…Starting with Nasrallah et al 's study, a decreased hippocampal NAA level was supported by several other studies in schizophrenia patients, and it was reported that NAA decrease in the hippocampus was approximately 22% (52). Considering that the decrease in hippocampal NAA levels is a more consistent result when compared to those in other brain areas such as the frontal cortex, basal ganglion, thalamus, and cingulate cortex in CSPs, it may be interpreted as strong evidence for neuronal/axonal loss in the hippocampus in schizophrenia (14,16,20,(53)(54)(55). In our study, similar to these results, NAA levels in the hippocampus were significantly decreased in the CSPs when compared to healthy controls.…”

Section: Discussionsupporting

confidence: 69%

“…However, several studies reported decreased PFC NAA levels in medicated chronic schizophrenia patients (CSPs) (8,9), first episode patients (FEPs) (7,10,11), and medicated schizophreniform spectrum patients (12). Similarly, several studies reported decreased hippocampal NAA levels (4), and a few studies reported unaltered NAA levels in chronic patients (13,14) and in medicated and unmedicated FEPs (15)(16)(17). Contrasting the above results, FEPs and drug-naive schizophrenia patients showed decreased hippocampal NAA/Cre ratios compared to medicated FEP (18).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

1H-magnetic resonance spectroscopy in first episode and chronic schizophrenia patients

Kirtaş¹,

Karadağ²,

Şengül³

et al. 2016

Turk J Med Sci

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

1H-magnetic resonance spectroscopy in first episode and chronic schizophrenia patients

Kirtaş¹,

Karadağ²,

Şengül³

et al. 2016

Turk J Med Sci

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“…In vivo measurements of cortical neurochemistry using proton magnetic resonance spectroscopy (1H MRS) revealed a reduction of N-acetylaspartate (NAA) in the hippocampus of schizophrenia patients (Steen et al 2005), pointing to a disturbed neuronal integrity and synaptic abundance (Maier et al 1995;Yildiz-Yesiloglu and Ankerst 2006). One recent study found a coexistent neurochemical and structural defi cit in the hippocampus of these patients, which might emphasize the role of the hippocampus in the pathogenesis of schizophrenia (Klar et al 2010).…”

Section: Subjectsmentioning

confidence: 99%

Hippocampal integrity and neurocognition in first-episode schizophrenia: A multidimensional study

Hasan

Wobrock

Falkai

et al. 2011

The World Journal of Biological Psychiatry

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“…A meta-analysis revealed consistently decreased N-acetylaspartate (NAA) concentrations across different brain regions (18). This finding has received further support from recent studies in hippocampus (19), striatum (20,21), thalamus (22), and ACC (23). Others have demonstrated increased NAA levels in hippocampus of chronic patients (24) and prefrontal cortex of high-risk adolescents (21).…”

mentioning

confidence: 87%

N-Acetylcysteine Normalizes Neurochemical Changes in the Glutathione-Deficient Schizophrenia Mouse Model During Development

Kulak¹

2012

Schizophrenia Research

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Background: Glutathione (GSH) is the major cellular redox-regulator and antioxidant. Redox-imbalance due to genetically impaired GSH synthesis is among the risk factors for schizophrenia. Here we used a mouse model with chronic GSH deficit induced by knockout (KO) of the key GSH-synthesizing enzyme, glutamate-cysteine ligase modulatory subunit (GCLM). Methods:With high-resolution magnetic resonance spectroscopy at 14.1 T, we determined the neurochemical profile of GCLM-KO, heterozygous, and wild-type mice in anterior cortex throughout development in a longitudinal study design.Results: Chronic GSH deficit was accompanied by an elevation of glutamine (Gln), glutamate (Glu), Gln/Glu, N-acetylaspartate, myoInositol, lactate, and alanine. Changes were predominantly present at prepubertal ages (postnatal days 20 and 30). Treatment with N-acetylcysteine from gestation on normalized most neurochemical alterations to wild-type level. Conclusions:Changes observed in GCLM-KO anterior cortex, notably the increase in Gln, Glu, and Gln/Glu, were similar to those reported in early schizophrenia, emphasizing the link between redox imbalance and the disease and validating the model. The data also highlight the prepubertal period as a sensitive time for redox-related neurochemical changes and demonstrate beneficial effects of early N-acetylcysteine treatment. Moreover, the data demonstrate the translational value of magnetic resonance spectroscopy to study brain disease in preclinical models.Key Words: Glutathione, MRS, N-acetylcysteine, neurochemical profile, oxidative stress, schizophrenia O xidative stress and impaired redox-regulation occur in neurodegenerative diseases such as Parkinson's (1), Alzheimer's (2), and Huntington disease (3), as well as in psychiatric pathologies including bipolar disorder (4) and schizophrenia (5). Whereas redox-dysregulation in neurodegenerative diseases is likely a downstream consequence of other primary causes, compelling data suggest that redox-dysregulation is a primary risk factor for schizophrenia (5). Indeed, glutathione (GSH), the major cellular redox-regulator and antioxidant, is decreased in cerebrospinal fluid, medial prefrontal cortex (6,7) and postmortem striatum (8) of schizophrenia patients. Furthermore, the two genes coding for the key GSH-synthesizing enzyme, glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunits, are associated with schizophrenia (9,10). Polymorphisms of trinucleotide repeats on the GCLC gene are accompanied by reduced enzyme activity, decreased GSH levels, and higher risk for the disease (10). Moreover, the response to an oxidative stress challenge in patient fibroblasts is depressed (10), indicating a deficit in GSH regulation. Thus, in combination with environmental insults that generate oxidative stress, this redox dysregulation may play a central role in schizophrenia (5,11).To investigate the link between redox imbalance and the disease, we study mice with genetic deletion (knockout) of the GCLM gene (KO) (12), which display a sustained...

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Interaction of hippocampal volume and N-acetylaspartate concentration deficits in schizophrenia: A combined MRI and 1H-MRS study

Cited by 36 publications

References 67 publications

1H-magnetic resonance spectroscopy in first episode and chronic schizophrenia patients

1H-magnetic resonance spectroscopy in first episode and chronic schizophrenia patients

Hippocampal integrity and neurocognition in first-episode schizophrenia: A multidimensional study

N-Acetylcysteine Normalizes Neurochemical Changes in the Glutathione-Deficient Schizophrenia Mouse Model During Development

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