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Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia.

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.

SUBMITTER: McQueen G

PROVIDER: S-EPMC7018675 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia.

McQueen Grant G Lay Aderlee A Lally John J Gabay Anthony S AS Collier Tracy T Lythgoe David J DJ Barker Gareth J GJ Stone James M JM McGuire Philip P MacCabe James H JH Egerton Alice A

Psychopharmacology 20191130 2

<h4>Rationale</h4>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.<h4>Objectives</h4>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 b ...[more]

PMID: 31786651

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Project description:The reliability of magnetoencephalography (MEG) resting-state functional connectivity in schizophrenia (SZ) is unknown as previous research has focused on healthy controls (HC). Here, we examined reliability in 26 participants (13-SZ, 13-HC). Eyes opened and eyes closed resting-state data were collected on 4 separate occasions during 2 visits, 1 week apart. For source modeling, we used minimum norm software to apply dynamic statistical parametric mapping. Source analyses compared the following functional connectivity metrics from each data run: coherence (coh), imaginary coherence (imcoh), pairwise phase consistency (ppc), phase-locking value (plv), phase lag index (pli), weighted phase lag index (wpli), and weighted phase lag index debiased (wpli2). Intraclass correlation coefficients (ICCs) were calculated for whole brain, network, and network pair averages. For reliability, ICCs above 0.75 = excellent, above 0.60 = good, above 0.40 = fair, and below 0.40 = poor reliability. We found the reliability of these metrics varied greatly depending on frequency band, network, network pair, and participant group examined. Broadband (1-58 Hz) whole brain averages in both HC and SZ showed excellent reliability for wpli2, and good to fair reliability for ppc, plv, and coh. Broadband network averages showed excellent to good reliability across 1 hour and 1 week for coh, imcoh, ppc, plv, wpli within default mode, cognitive control, and visual networks in HC, while the same metrics had excellent to fair reliability in SZ. Regional network pair averages showed good to fair reliability for coh, ppc, plv within default mode, cognitive control and visual network pairs in HC and SZ. In general, HC had higher reliability compared to SZ, and the default mode, cognitive control, and visual networks had higher reliability compared to somatosensory and auditory networks. Similar reliability levels occurred for both eyes opened and eyes closed resting-states for most metrics. The functional connectivity metrics of coh, ppc, and plv performed best across 1 hour and 1 week in HC and SZ. We also found that SZ had reduced coh, plv, and ppc in the dmn average and pair values indicating dysconnectivity in SZ. These findings encourage collecting both eyes opened and eyes closed resting-state MEG, while demonstrating that clinical populations may differ in reliability.

Project description:Introduction: An important but under-investigated confound of functional magnetic resonance imaging (fMRI) is body posture. Although it is well established that body position changes cerebral blood flow, the amount of cerebrospinal fluid in the brain, intracranial pressure, and even the firing rate of certain cell types, there is currently no study that directly examines its effect on fMRI measurements. Moreover, fMRI is typically done in a supine position, which often does not correspond to how these processes are performed in everyday settings. Methods: In this study, 20 healthy adults underwent resting-state fMRI under three body positions: supine, right lateral decubitus (RLD), and left lateral decubitus (LLD). We first investigated whether there were differences in overall organization of whole-brain connectivity between conditions using graph theory. Second, we examined whether functional connectivity of two most studied default mode network (DMN) seeds to the rest of the brain was altered as a function of body position. Results: Nonparametric statistical analyses revealed that global network measures differed among conditions, with the supine and LLD showing identical results which differed when compared to the RLD. There was decreased connectivity for DMN seeds in the RLD condition compared to the supine and LLD, but there were no significant differences between the latter two conditions. Discussion: Potential mechanisms underlying these alterations include gravity, changes in physiology, and body anatomy. Our results suggest that, compared to supine and LLD, the RLD position leads to changes in whole-brain and DMN connectivity. Finally, depending on the research question, combining imaging modalities that allow for more naturalistic settings provides a better understanding of certain phenomena. Impact statement Functional connectivity is sensitive to several confounds, including motion, heart rate, and respiration. Body posture is also an important but under-investigated confound. In this study, healthy adults were scanned in three different positions to investigate whether posture results in changes in connectivity. We found that connectivity was identical if participants were facing up or lying on their left, but it was altered when they were lying on their right. Results suggest that posture can lead to connectivity changes and, in some cases, the combined use of functional magnetic resonance imaging with other techniques might provide a better understanding of the phenomenon of interest.

Dataset Information

Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia.

Publications

Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia.

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