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Int J Neuropsychopharmacol. 2019 Aug 1;22(8):478-487. doi: 10.1093/ijnp/pyz022.

N-Acetyl-Cysteine Supplementation Improves Functional Connectivity Within the Cingulate Cortex in Early Psychosis: A Pilot Study.

Author information

1
Department of Radiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
2
Turku Brain and Mind Center, University of Turku, Turku, Finland.
3
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
4
Dutch Connectome Lab, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU Amsterdam, Amsterdam, The Netherlands.
5
Medical Image Analysis Laboratory (MIAL), Centre d'Imagerie BioMédicale (CIBM), Lausanne, Switzerland.
6
Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
7
Treatment and Early Intervention in Psychosis Program (TIPP), Service of General Psychiatry, Department of Psychiatry, Lausanne, Switzerland.

Abstract

BACKGROUND:

There is increasing evidence that redox dysregulation, which can lead to oxidative stress and eventually to impairment of oligodendrocytes and parvalbumin interneurons, may underlie brain connectivity alterations in schizophrenia. Accordingly, we previously reported that levels of brain antioxidant glutathione in the medial prefrontal cortex were positively correlated with increased functional connectivity along the cingulum bundle in healthy controls but not in early psychosis patients. In a recent randomized controlled trial, we observed that 6-month supplementation with a glutathione precursor, N-acetyl-cysteine, increased brain glutathione levels and improved symptomatic expression and processing speed.

METHODS:

We investigated the effect of N-acetyl-cysteine supplementation on the functional connectivity between regions of the cingulate cortex, which have been linked to positive symptoms and processing speed decline. In this pilot study, we compared structural connectivity and resting-state functional connectivity between early psychosis patients treated with 6-month N-acetyl-cysteine (n = 9) or placebo (n = 11) supplementation with sex- and age-matched healthy control subjects (n = 74).

RESULTS:

We observed that 6-month N-acetyl-cysteine supplementation increases functional connectivity along the cingulum and more precisely between the caudal anterior part and the isthmus of the cingulate cortex. These functional changes can be partially explained by an increase of centrality of these regions in the functional brain network.

CONCLUSIONS:

N-acetyl-cysteine supplementation has a positive effect on functional connectivity within the cingulate cortex in early psychosis patients. To our knowledge, this is the first study suggesting that increased brain glutathione levels via N-acetyl-cysteine supplementation may improve brain functional connectivity.

KEYWORDS:

N-acetyl-cysteine; cingulate cortex; early psychosis; functional connectivity

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