Metabolite profiles in the anterior cingulate cortex of depressed patients differentiate those taking N-acetyl-cysteine versus placebo

Das, Pritha, Tanious, Michelle, Fritz, Kristina, Dodd, Seetal, Dean, Olivia M., Berk, Michael and Malhi, Gin S. 2013, Metabolite profiles in the anterior cingulate cortex of depressed patients differentiate those taking N-acetyl-cysteine versus placebo, Australian and New Zealand journal of psychiatry, vol. 47, no. 4, pp. 347-354, doi: 10.1177/0004867412474074.

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Title Metabolite profiles in the anterior cingulate cortex of depressed patients differentiate those taking N-acetyl-cysteine versus placebo
Author(s) Das, Pritha
Tanious, Michelle
Fritz, Kristina
Dodd, SeetalORCID iD for Dodd, Seetal
Dean, Olivia M.ORCID iD for Dean, Olivia M.
Berk, MichaelORCID iD for Berk, Michael
Malhi, Gin S.
Journal name Australian and New Zealand journal of psychiatry
Volume number 47
Issue number 4
Start page 347
End page 354
Total pages 8
Publisher SAGE Publications
Place of publication London, England
Publication date 2013-04
ISSN 0004-8674
Keyword(s) anterior cingulate cortex
major depressive disorder
proton magnetic spectroscopy
Summary Background: Increased oxidative stress is thought to contribute to the pathophysiology of major depressive disorder (MDD), which is in part due to diminished levels of glutathione, the primary anti-oxidant of the brain. Oral administration of N-acetyl-cysteine (NAC) replenishes glutathione and has therefore been shown to reduce depressive symptoms. Proton magnetic spectroscopy (1H-MRS) that allows quantification of brain metabolites pertinent to both MDD and oxidative biology may provide some novel insights into the neurobiological effects of NAC, and in particular metabolite concentrations within the anterior cingulate cortex (ACC) are likely to be important given the key role of this region in the regulation of affect.

Objective: The aim of this study was to determine whether the metabolite profile of the ACC in MDD patients predicts treatment with adjunctive NAC versus placebo.

Methods: This study was nested within a multicentre, randomized, double-blind, placebo-controlled study of MDD participants treated with adjunctive NAC. Participants (n = 76) from one site completed the spectroscopy component at the end of treatment (12 weeks). Spectra from a single-voxel in the ACC were acquired and absolute concentrations of glutamate (Glu), glutamate-glutamine (Glx), N-acetyl-aspartate (NAA) and myo-inositol (mI) were obtained. Binary logistic regression analysis was performed to determine whether metabolite profiles could predict NAC versus placebo group membership.

Results: When predicting group outcome (NAC or placebo), Glx, NAA and mI were a significant model, and had 75% accuracy, while controlling for depression severity and sex. However, the Glu, NAA and mI profile was only predictive at a trend level, with 68.3% accuracy. For both models, the log of the odds of a participant being in the NAC group was positively related to NAA, Glx and Glu levels and negatively related to mI levels.

Conclusion: The finding of higher Glx and NAA levels being predictive of the NAC group provides preliminary support for the putative anti-oxidative role of NAC in MDD.
Language eng
DOI 10.1177/0004867412474074
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Grant ID NHMRC 628395
Copyright notice ©2013, The Royal Australian and New Zealand College of Psychiatrists
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Created: Thu, 28 Mar 2013, 10:39:37 EST by Jane Moschetti

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