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

Das, Pritha; Tanious, Michelle; Fritz, Kristina; Dodd, Seetal; Dean, Olivia; Berk, Michael; Malhi, Gin S

doi:10.1177/0004867412474074

Cited by 24 publications

(15 citation statements)

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“… 49 ) More recently, patients with major depressive disorder (MDD) supplemented with NAC were found to have increased levels of NAC metabolites (necessary for GSH production) in the anterior cingulate cortex detected by proton magnetic spectroscopy. 50 ) These studies suggest that NAC does initiate effects in the brain. It has been postulated that cysteine may cross the BBB via a sodium-dependent transport system where it is converted into cystine, the di-sulfide derivative of cysteine.…”

Section: Introductionmentioning

confidence: 86%

N-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review

Oliver

Dean

Camfield

et al. 2015

Clin Psychopharmacol Neurosci

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ObjectiveObsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area.MethodsPubMed, Web of Science and Cochrane Library Database were searched for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder (OCD) or obsessive compulsive related disorders. Researchers with known involvement in NAC studies were contacted for any unpublished data.ResultsFour clinical trials and five case reports/series were identified. Study durations were commonly 12-weeks, using 2,400–3,000 mg/day of NAC. Overall, NAC demonstrates activity in reducing the severity of symptoms, with a good tolerability profile and minimal adverse effects. Currently there are three ongoing randomized controlled trials using NAC for OCD (two adults and one pediatric), and one for excoriation.ConclusionEncouraging results have been demonstrated from the few pilot studies that have been conducted. These results are detailed, in addition to a discussion of future potential research.

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Section: Introductionmentioning

confidence: 86%

N-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review

Oliver

Dean

Camfield

et al. 2015

Clin Psychopharmacol Neurosci

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“…In this context, spectroscopy data suggest a role of N-acetylcysteine on glutamate-glutamine, N-acetylaspartate, and myo-inositol. 31 Depression is extensively documented to be associated with oxidative stress; for comprehensive reviews of the topic, see Hardan et al 32 and Garcia et al 33 N-acetylcysteine counters the effects of reactive oxidative species and gradually rectifies the abnormalities in oxidative biology, inflammation, apoptosis, and mitochondrial function found in depression. [34][35][36][37] N-acetylcysteine may be addressing any of these multiple pathways to neuroprogression that are described in depression.…”

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confidence: 99%

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

Berk

Dean²,

Cotton³

et al. 2014

J. Clin. Psychiatry

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138

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Objective: Major depressive disorder (MDD) is one of the most common psychiatric disorders, conferring considerable individual, family, and community burden. To date, treatments for MDD have been derived from the monoamine hypothesis, and there is a paucity of emerging antidepressants, especially with novel mechanisms of action and treatment targets. N-acetylcysteine (NAC) is a redox-active glutathione precursor that decreases inflammatory cytokines, modulates glutamate, promotes neurogenesis, and decreases apoptosis, all of which contribute to the neurobiology of depression.Method: Participants with a current episode of MDD diagnosed according to DSM-IV-TR criteria (N = 252) were treated with NAC or placebo in addition to treatment as usual for 12 weeks and were followed to 16 weeks. Data were collected between 2007 and 2011. Results:The omnibus interaction between group and visit for the Montgomery-Asberg Depression Rating Scale (MADRS), the primary outcome measure, was not significant (F 1,520.9 = 1.98, P = .067), and the groups did not separate at week 12 (t 360.3 = −1.12, P = .265). However, at week 12, the scores on the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) differed from placebo (P = .03). Among participants with a MADRS score ≥ 25, NAC separated from placebo at weeks 6, 8, 12, and 16 (P < .05). Additionally, the rate of change between baseline and week 16 was significant (t 221.03 = −2.11, P = .036). NAC treatment was superior to placebo at week 16 for secondary readouts of function and clinical impression. Remission and response were greater in the NAC group at week 16, but not at week 12. The NAC group had a greater rate of gastrointestinal and musculoskeletal adverse events. Conclusions:Being negative at the week 12 end point, and with some positive secondary signals, the study provides only limited support for the role of NAC as a novel adjunctive therapy for MDD. These data implicate the pathways influenced by NAC in depression pathogenesis, principally oxidative and inflammatory stress and glutamate, although definitive confirmation remains necessary.Trial Registration: www.anzctr.org.au Identifier: ACTRN12607000134426 Clin Psychiatry 2014;75(6):628-636 J

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“…Decreased activation in the anterior cingulate gyrus has been reported in depression, and the magnitude of anterior cingulate activity has been found to predict treatment response, with lower activation during an acute episode predicting a worse response to treatment ( Seminowicz et al, 2004 ). Treatment-related changes in the activation of different regions of the anterior cingulate gyrus have also been reported, with the most common finding being an increase in activation in the hypoactive regions during an acute depressive episode ( Kennedy et al, 2001 ; Das et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Abnormal Anterior Cingulate N-Acetylaspartate and Executive Functioning in Treatment-Resistant Depression After rTMS Therapy

Zheng

Jia

Guo

et al. 2015

IJNPPY

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Background:Cognitive impairment is a key feature of treatment-resistant depression (TRD) and can be related to the anterior cingulate cortex (ACC) function. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. However, no studies to date have investigated the association between neurobiochemical changes within the anterior cingulate and executive dysfunction measured in TRD being treated with rTMS.Methods:Thirty-two young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study [active (n=18) vs. sham (n=14)]. ACC metabolism was investigated before and after high-frequency (15Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). The results were compared with 28 age- and gender-matched healthy controls. Executive functioning was measured with the Wisconsin Card Sorting Test (WCST) among 34 subjects with TRD and 28 healthy subjects.Results:Significant reductions in N-acetylaspartate (NAA) and choline-containingCompound levels in the left ACC were found in subjects with TRD pre-rTMS when compared with healthy controls. After successful treatment, NAA levels increased significantly in the left ACC of subjects and were not different from those of age-matched controls. In the WCST, more perseverative errors and fewer correct numbers were observed in TRD subjects at baseline. Improvements in both perseverative errors and correct numbers occurred after active rTMS. In addition, improvement of perseverative errors was positively correlated with enhancement of NAA levels in the left ACC in the active rTMS group.Conclusions:Our results suggest that the NAA concentration in the left ACC is associated with an improvement in cognitive functioning among subjects with TRD response to active rTMS.

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

Abstract: 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.

Cited by 24 publications

References 43 publications

N-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review

N-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

Abnormal Anterior Cingulate N-Acetylaspartate and Executive Functioning in Treatment-Resistant Depression After rTMS Therapy

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