McQueen, Grant, Lay, Aderlee, Lally, John, Gabay, Anthony S, Collier, Tracy, Lythgoe, David J, Barker, Gareth J, Stone, James M, McGuire, Philip, MacCabe, James H and Egerton, Alice (2020) Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia. Psychopharmacology, 237. pp. 443-451. ISSN 0033-3158

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Abstract

Rationale
There is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce.

Objectives
The aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC).

Methods
In a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions.

Results
Compared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6).

Conclusions
These findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of interest.

Item Type:	Article
Keywords:	Functional connectivity, Glutamate, Magnetic resonance imaging, Magnetic resonance spectroscopy, Resting state, Schizophrenia, n-Acetylcysteine, Acetylcysteine, Adult, Brain, Cross-Over Studies, Double-Blind Method, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Proton Magnetic Resonance Spectroscopy, Rest, Schizophrenia
Schools and Departments:	Brighton and Sussex Medical School > Neuroscience
SWORD Depositor:	Mx Elements Account
Depositing User:	Mx Elements Account
Date Deposited:	03 Oct 2022 13:12
Last Modified:	03 Oct 2022 13:15
URI:	http://sro.sussex.ac.uk/id/eprint/108263

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