Reduced Concentrations of Thalamic <i>N</i>-Acetylaspartate in Male Patients With Schizophrenia

Deicken, Raymond F.; Johnson, Camilla; Eliaz, Y.; Schuff, Norbert

doi:10.1176/appi.ajp.157.4.644

Cited by 57 publications

(36 citation statements)

References 23 publications

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“…Altered glutamatergic NMDA receptor expression [17] and synaptic dysfunction or loss [18] have also been detected in the anterior and mediodorsal thalamic nuclei in patients with schizophrenia. Most importantly, our findings support and extend the results of previous spectroscopic investigations with voxels localized to the mediodorsal and anterior regions of the thalamus [26]- [28]. Those studies also found NAA deficits in patients with schizophrenia, but did not examine the pulvinar region.…”

Section: Discussionsupporting

confidence: 91%

“…Discrepancies are thought to be due to several factors such as varying voxel size, position, and slice thickness; averaging many voxels over a large region; and voxel tissue heterogeneity. Studies with more localized voxel placement have detected reduced bilateral mediodorsal and anterior thalamic NAA levels in schizophrenia [26]- [28]. However, these studies did not examine additional thalamic subregions.…”

Section: A Neuroimaging Studies Of the Thalamusmentioning

confidence: 95%

“…NAA concentrations in the thalamus may also reveal key neuroanatomical alterations in schizophrenia. Recent studies comparing schizophrenics with controls have noted: 1) reduced thalamic NAA levels in schizophrenia [26]- [28]; and 2) no group differences in NAA levels [29]- [31]. Discrepancies are thought to be due to several factors such as varying voxel size, position, and slice thickness; averaging many voxels over a large region; and voxel tissue heterogeneity.…”

Section: A Neuroimaging Studies Of the Thalamusmentioning

confidence: 99%

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Automatic Relevance Determination for Identifying Thalamic Regions Implicated in Schizophrenia

Browne

Jakary

Vinogradov

et al. 2008

IEEE Trans. Neural Netw.

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Abstract-There have been many theories about and computational models of the schizophrenic disease state. Brain imaging techniques have suggested that abnormalities of the thalamus may contribute to the pathophysiology of schizophrenia. Several studies have found the thalamus to be altered in schizophrenia, and the thalamus has connections with other brain structures implicated in the disorder. This paper describes an experiment examining thalamic levels of the metabolite N-acetylaspartate (NAA), taken from schizophrenics and controls using in vivo proton magnetic resonance spectroscopic imaging. Automatic relevance determination was performed on neural networks trained on this data, identifying NAA group differences in the pulvinar and mediodorsal nucleus, underscoring the importance of examining thalamic subregions in schizophrenia.

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Section: Discussionsupporting

confidence: 91%

Section: A Neuroimaging Studies Of the Thalamusmentioning

confidence: 95%

Section: A Neuroimaging Studies Of the Thalamusmentioning

confidence: 99%

See 1 more Smart Citation

Automatic Relevance Determination for Identifying Thalamic Regions Implicated in Schizophrenia

Browne

Jakary

Vinogradov

et al. 2008

IEEE Trans. Neural Netw.

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“…The reduced NAA levels correlated with the severity of negative symptoms and poor performance in the Wisconsin Card Sorting Test. Other brain regions where NAA reductions have been reported in schizophrenia include the thalamus (Deicken et al, 2000a;Ende et al, 2003;Jakary et al, 2005), anterior cingulate cortex (Deicken et al, 1997) and the cerebellum (Ende et al, 2005).…”

Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,215

1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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“…While there was no significant difference in metabolite levels and ratios when compared with the control cases (20,21,(62)(63)(64), decreases in NAA and NAA/ Cre ratios were reported in some studies. It was determined that thalamic NAA, Cre, and Cho levels were decreased in male patients, children and adolescent patients with schizophrenia, and individuals who had high genetic risk for schizophrenia (4,28,65). Additionally, it has been reported that decreased NAA or NAA/Cho levels were associated with acute psychotic attack, active auditory hallucinations, and typical antipsychotic use in the CSP group (66)(67)(68)(69).…”

Section: Discussionmentioning

confidence: 99%

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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Reduced Concentrations of Thalamic N-Acetylaspartate in Male Patients With Schizophrenia

Abstract: The finding of reduced concentrations of N-acetylaspartate bilaterally suggests neuronal dysfunction and/or loss in both the right and left thalamic regions in male patients with schizophrenia.

Cited by 57 publications

References 23 publications

Automatic Relevance Determination for Identifying Thalamic Regions Implicated in Schizophrenia

Automatic Relevance Determination for Identifying Thalamic Regions Implicated in Schizophrenia

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

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

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