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

Volumn 47, Issue 4, 2013, Pages 347-354

  Das, Pritha ^a,b,c   Tanious, Michelle ^a,b,c   Fritz, Kristina ^a,b,c   Dodd, Seetal ^d,e,f,g   Dean, Olivia M ^d,e,f,g   Berk, Michael ^e,f,g   Malhi, Gin S ^a,b,c  

^a UNIVERSITY OF SYDNEY   (Australia)

^b ROYAL NORTH SHORE HOSPITAL   (Australia)

^c UNIVERSITY OF SYDNEY   (Australia)

^d THE NATIONAL CENTRE OF EXCELLENCE IN YOUTH MENTAL HEALTH   (Australia)

^e DEAKIN UNIVERSITY   (Australia)

^f FLOREY INSTITUTE OF NEUROSCIENCE AND MENTAL HEALTH   (Australia)

^g UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Anterior cingulate cortex; Major depressive disorder; N acetyl cysteine; Proton magnetic spectroscopy

Indexed keywords

ACETYLCYSTEINE; GLUTAMIC ACID; GLUTAMINE; GLUTATHIONE; PLACEBO;

ACCURACY; ADULT; ANTERIOR CINGULATE; ANTIOXIDANT ACTIVITY; ARTICLE; BRAIN REGION; CONTROLLED STUDY; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; FEMALE; FRONTAL CORTEX; GRAY MATTER; HUMAN; MAJOR CLINICAL STUDY; MAJOR DEPRESSION; MALE; MENTAL PATIENT; METABOLITE; MONTGOMERY ASBERG DEPRESSION RATING SCALE; MULTICENTER STUDY; NUCLEAR MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; PREDICTIVE VALUE; PROTON NUCLEAR MAGNETIC RESONANCE; PSYCHOTHERAPY; RANDOMIZED CONTROLLED TRIAL; SIGNAL NOISE RATIO; SPECTROSCOPY; TREATMENT DURATION;

ACETYLCYSTEINE; ASPARTIC ACID; DEPRESSIVE DISORDER, MAJOR; DOUBLE-BLIND METHOD; FEMALE; FREE RADICAL SCAVENGERS; FUNCTIONAL NEUROIMAGING; GLUTAMIC ACID; GLUTAMINE; GYRUS CINGULI; HUMANS; INOSITOL; MALE; MIDDLE AGED; OXIDATIVE STRESS;

EID: 84880562183     PISSN: 00048674     EISSN: 14401614     Source Type: Journal    
DOI: 10.1177/0004867412474074     Document Type: Article

References (44)

1. Arun P, Moffett JR and Namboodiri AMA (2009) Evidence for mitochondrial and cytoplasmic N-acetylaspartate synthesis in SH-SY5Y neuroblastoma cells. Neurochemistry International 55: 219-225.
2. Auer DP, Pütz B, Kraft E, et al. (2000) Reduced glutamate in the anterior cingulate cortex in depression: An in vivo proton magnetic resonance spectroscopy study. Biological Psychiatry 47: 305-313.
3. Berk M, Copolov DL, Dean O, et al. (2008a) N-Acetyl cysteine for depressive symptoms in bipolar disorder-A double-blind randomized placebo- controlled trial. Biological Psychiatry 64: 468-475.
4. Berk M, Dean O, Cotton SM, et al. (2013) The efficacy of adjunctive N-acetyl cysteine in major depression: A double-blind, randomised, placebo-controlled trial (submitted).
5. Berk M, Ng F, Dean O, et al. (2008b) Glutathione: A novel treatment target in psychiatry. Trends in Pharmacological Sciences 29: 346-351.
6. Bush G, Luu P and Posner MI (2000) Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences 4: 215-222.
7. Charney DS and Manji HK (2004) Life stress, genes, and depression: Multiple pathways lead to increased risk and new opportunities for intervention. Science's STKE 2004(225): re5.
8. Chung C (2012) New perspectives on glutamate receptor antagonists as antidepressants. Archives of Pharmacal Research 35: 573-577.
9. Coupland NJ, Ogilvie CJ, Hegadoren KM, et al. (2005) Decreased prefrontal myo-inositol in major depressive disorder. Biological Psychiatry 57: 1526-1534.
10. Currie S, Hadjivassiliou M, Craven IJ, et al. (2012) Magnetic resonance spectroscopy of the brain. Postgraduate Medical Journal. Epub ahead of print, 26 September 2012.
11. Dean O, Giorlando F and Berk M (2011) N-Acetylcysteine in psychiatry: Current therapeutic evidence and potential mechanisms of action. Journal of Psychiatry and Neuroscience JPN 36: 78-86.
12. Dodd S, Dean O, Copolov DL, et al. (2008) N-Acetylcysteine for antioxidant therapy: Pharmacology and clinical utility. Expert Opinion on Biological Therapy 8: 1955-1962.
13. Drevets WC, Savitz J and Trimble M (2008) The subgenual anterior cingulate cortex in mood disorders. CNS Spectrums 13: 663-681.
14. Dringen R (2000) Metabolism and functions of glutathione in brain. Progress in Neurobiology 62: 649-671.
15. Feighner JP (1999) Mechanism of action of antidepressant medications. Journal of Clinical Psychiatry 60: 4-11.
16. Frey R, Metzler D, Fischer P, et al. (1998) Myo-inositol in depressive and healthy subjects determined by frontal 1H-magnetic resonance spectroscopy at 1. 5 tesla. Journal of Psychiatric Research 32: 411-420.
17. Gasparovic C, Song T, Devier D, et al. (2006) Use of tissue water as a concentration reference for proton spectroscopic imaging. Magnetic Resonance in Medicine 55: 1219-1226.
18. Gonul AS, Kitis O, Ozan E, et al. (2006) The effect of antidepressant treatment on N-acetyl aspartate levels of medial frontal cortex in drugfree depressed patients. Progress in Neuro-Psychopharmacology and Biological Psychiatry 30: 120-125.
19. Halliwell B (2006) Oxidative stress and neurodegeneration: Where are we now? Journal of Neurochemistry 97: 1634-1658.
20. Heales R, Davies SEC, Bates TE, et al. (1995) Depletion of brain glutathione is accompanied by impaired mitochondrial function and decreased N-acetyl aspartate concentration. Neurochemical Research 20: 31-38.
21. Horn DI, Yu C, Steiner J, et al. (2010) Glutamatergic and resting-state functional connectivity correlates of severity in major depression - The role of pregenual anterior cingulate cortex and anterior insula. Frontiers in Systems Neuroscience 4: 33.
22. Kaymak SU, Demir B, Oguz KK, et al. (2009) Antidepressant effect detected on proton magnetic resonance spectroscopy in drug-naive female patients with first-episode major depression. Psychiatry and Clinical Neurosciences 63: 350-356.
23. Kirsch I (2009) Antidepressants and the placebo response. Epidemiologia e Psichiatria Sociale 18: 318-322.
24. Kodydková J, Vávrová L, Zeman M, et al. (2009) Antioxidative enzymes and increased oxidative stress in depressive women. Clinical Biochemistry 42: 1368-1374.
25. Kumar A, Thomas A, Lavretsky H, et al. (2002) Frontal white matter biochemical abnormalities in late-life major depression detected with proton magnetic resonance spectroscopy. American Journal of Psychiatry 159: 630-636.
26. Luykx JJ, Laban KG, van den Heuvel MP, et al. (2012) Region and state specific glutamate downregulation in major depressive disorder: A meta-analysis of 1H-MRS findings. Neuroscience and Biobehavioral Reviews 36: 198-205.
27. Maes M, Galecki P, Chang YS, et al. (2011) A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35: 676-692.
28. Magalhães PV, Dean OM, Bush AI, et al. (2011) Dimensions of improvement in a clinical trial of N-acetyl cysteine for bipolar disorder. Acta Neuropsychiatrica 23: 87-88.
29. Malhi GS, Tanious M and Das P (2011) Spectroscopy: A clinical perspective. Acta Neuropsychiatrica 23: 78-79.
30. Malhi GS, Tanious M, Das P, et al. (2013) Potential mechanisms of action of lithium in bipolar disorder: Current understanding. CNS Drugs 27 (in press).
31. Malhi GS, Valenzuela M, Wen W, et al. (2002) Magnetic resonance spectroscopy and its applications in psychiatry. Australian and New Zealand Journal of Psychiatry 36: 31-43.
32. Mirza Y, Tang J, Russell A, et al. (2004) Reduced anterior cingulate cortex glutamatergic concentrations in childhood major depression. Journal of the American Academy of Child and Adolescent Psychiatry 43: 341-348.
33. Montgomery SA and Asberg M (1979) A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134: 382-389.
34. Ozcan EM, Gulec M, Ozerol E, et al. (2004) Antioxidant enzyme activities and oxidative stress in affective disorders. International Clinical Psychopharmacology 19: 89-95.
35. Paus T (2001) Primate anterior cingulate cortex: Where motor control, drive and cognition interface. Nature Reviews. Neuroscience 2: 417-424.
36. Pfleiderer B, Michael N, Erfurth A, et al. (2003) Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Psychiatry Research: Neuroimaging 122: 185-192.
37. Portella MJ, de Diego-Adelino J, Gomez-Anson B, et al. (2011) Ventromedial prefrontal spectroscopic abnormalities over the course of depression: A comparison among first episode, remitted recurrent and chronic patients. Journal of Psychiatric Research 45: 427-434.
38. Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR in Biomedicine 14: 260-264.
39. Rothman DL, Sibson NR, Hyder F, et al. (1999) In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate-glutamine neurotransmitter cycle and functional neuroenergetics. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 354: 1165-1177.
40. Sanacora G, Zarate CA, Krystal JH, et al. (2008) Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nature Reviews. Drug Discovery 7: 426-437.
41. Silverstone PH, McGrath BM, Kim H, et al. (2005) Bipolar disorder and myo-inositol: A review of the magnetic resonance spectroscopy findings. Bipolar Disorders 7: 1-10.
42. Stanley JA (2002) In vivo magnetic resonance spectroscopy and its application to neuropsychiatric disorders. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie 47: 315-326.
43. Taylor MJ, Selvaraj S, Norbury R, et al. (2009) Normal glutamate but elevated myo-inositol in anterior cingulate cortex in recovered depressed patients. Journal of Affective Disorders 119: 186-189.
44. Wu G, Fang Y-Z, Yang S, et al. (2004) Glutathione metabolism and its implications for health. Journal of Nutrition 134: 489-492.