In this study, researchers gave NAC to mice from 5 days old (infancy) to 90 days old (mature adulthood.)
Strikingly, chronic treatment with the glutathione precursor N-acetylcysteine (NAC) from postnatal days 5-90 restored not only antioxidant-related mRNA expression and mitochondria numbers, but also myelin-related mRNA expression and mPFC-dependent cognitive dysfunction, while blood glutathione levels remained unaffected. The promyelinating effect of NAC was at least partly due to a positive effect on oligodendrocyte lineage progression. Together, our findings highlight that oxidative stress may contribute to cognitive symptoms in the APO-SUS rat model of SZ and encourage antioxidant therapy in early phases of SZ.
In this study NAC protected white matter in people with early phase schizophrenia. (There is also a trial underway using NAC in people at high risk.)
A group × time interaction indicated a difference in the 6-month evolution of white matter integrity (as measured by generalized fractional anisotropy, gFA) in favor of the NAC group, which showed an 11% increase.
Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [−5.97 (−10.44, −1.51), p = .009], PANSS negative [mean difference −1.83 (95% confidence interval: −3.33, −.32), p = .018], and PANSS general [−2.79 (−5.38, −.20), p = .035], CGI-Severity (CGI-S) [−.26 (−.44, −.08), p = .004], and CGI-Improvement (CGI-I) [−.22 (−.41, −.03), p = .025] scores. No significant change on the PANSS positive subscale was seen. N-acetyl cysteine treatment also was associated with an improvement in akathisia ( p = .022). Effect sizes at end point were consistent with moderate benefits.
The present study detected improvement in positive, negative, general and total psychopathology symptoms as well as cognitive performance with NAC treatment. It is also well-tolerated, safe and easy-to-use agent as an effective therapeutic strategy to improve outcome in schizophrenia treatment.
And this one where it was combined with risperidone and primarily improved negative symptoms.
By the study end point, NAC-treated patients showed significantly greater improvement in the PANSS total ( P = 0.006) and negative subscale ( P < 0.001) scores than that in the placebo group, but this difference was not significant for positive and general psychopathology subscales.