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    N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis.

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    Author
    Conus, P; Seidman, LJ; Fournier, M; Xin, L; Cleusix, M; Baumann, PS; Ferrari, C; Cousins, A; Alameda, L; Gholam-Rezaee, M; ...
    Date
    2018-02-15
    Source Title
    Schizophrenia Bulletin
    Publisher
    Oxford University Press (OUP)
    University of Melbourne Author/s
    Conus, Philippe
    Affiliation
    Centre for Youth Mental Health
    Metadata
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    Document Type
    Journal Article
    Citations
    Conus, P., Seidman, L. J., Fournier, M., Xin, L., Cleusix, M., Baumann, P. S., Ferrari, C., Cousins, A., Alameda, L., Gholam-Rezaee, M., Golay, P., Jenni, R., Woo, T. -U. W., Keshavan, M. S., Eap, C. B., Wojcik, J., Cuenod, M., Buclin, T., Gruetter, R. & Do, K. Q. (2018). N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis.. Schizophr Bull, 44 (2), pp.317-327. https://doi.org/10.1093/schbul/sbx093.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254978
    DOI
    10.1093/schbul/sbx093
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815074
    Abstract
    Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC's impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase activity [GPxBC]). No changes in negative or positive symptoms or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on neurocognition (processing speed). NAC also led to increases of GSHmPFC by 23% (P = .005) and GSHBC by 19% (P = .05). In patients with high-baseline GPxBC compared to low-baseline GPxBC, subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC. In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest baseline levels. However, NAC led to some neurocognitive improvements and an increase in brain GSH levels, indicating good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help identify a subgroup of patients who improve their positive symptoms with NAC. Thus, future trials with antioxidants in EP should consider biomarker-guided treatment.

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