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 S. Baumann, Paul Klauser, Martine Cleusix, Raoul Jenni, Yasser Alemàn-Gómez, Rolf Gruetter, Philippe Conus, Kim Q. Do, Patric Hagmann

Research output: Contribution to JournalArticleAcademicpeer-review


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
Number of pages10
JournalThe international journal of neuropsychopharmacology
Issue number8
Early online date8 Jul 2019
Publication statusPublished - Aug 2019


We thank all patients for their enduring participation. We are grateful for support from the Damm-Etienne Foundation and the Alamaya Foundation. We thank Bioadvantex Pharma, Inc. for providing NAC and placebo. We thank Elsevier Language Editing service for the English language editing. This work was supported by the Swiss National Science Foundation (320030_122419 to P.C. and K.Q.D.; 310030-156874 to P.H.; P2ELP3_172087 to A.G.), National Center of Competence in Research (NCCR) ‘SYNAPSY – The Synaptic Bases of Mental Diseases’ financed by the Swiss National (no. 51AU40_125759). T.R. received support from Emil Aaltonen (Finland), Technology Industries of Finland Centennial Foundation (Finland), Automation Foundation (Finland), and Oscar Öflunds Stiftelse (Finland). P.S.B. was supported by the Leenaards Foundation.

FundersFunder number
Alamaya Foundation
Automation Foundation
Damm-Etienne Foundation
Emil Aaltonen (Finland), Technology Industries of Finland Centennial Foundation
Swiss National51AU40_125759
nccr – on the move
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung310030-156874, P2ELP3_172087, 320030_122419
Oskar Öflunds Stiftelse
Fondation Leenaards


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


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