N-acetyl-cysteine supplementation improves functional connectivity within the cingulate cortex in early psychosis: A pilot study

Emeline Mullier, Timo Roine, Alessandra Griffa, Lijing Xin, Philipp Baumann, Paul Klauser, Martine Cleusix, Raoul Jenni, Yasser Aleman-Gomez, Rolf Gruetter, Philippe Conus, Kim Q. Do, Patric Hagmann

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
Pages (from-to)478–487
JournalINTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume22
Issue number8
DOIs
Publication statusPublished - 2019
MoE publication typeA1 Journal article-refereed

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    Mullier, E., Roine, T., Griffa, A., Xin, L., Baumann, P., Klauser, P., Cleusix, M., Jenni, R., Aleman-Gomez, Y., Gruetter, R., Conus, P., Do, K. Q., & Hagmann, P. (2019). N-acetyl-cysteine supplementation improves functional connectivity within the cingulate cortex in early psychosis: A pilot study. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 22(8), 478–487. https://doi.org/10.1093/ijnp/pyz022