SU19. Effects of N-Acetyl-Cysteine as an Add-on to Standard Treatment on Neurocognition in Early Psychosis

Background: Schizophrenia is associated with neurocognitive dysfunction already in the early phase of the disease.1 However, cognitive impairments are actually poorly treated by pharmacological interventions, leaving severe problems in functioning.2 Increasing evidence suggest oxidative stress and redox dysregulation play a role in the emergence of psychosis.3 In particular, levels of glutathione (GSH) are lower in chronic schizophrenia.4 In addition, a previous trial with the antioxidant N-acetyl-cysteine (NAC) led to negative symptoms reduction in chronic patients.5 Therefore, we explored if NAC had also an impact on neurocognition in early psychosis (EP) patients. Methods: The study was a 6-month, double-blind, randomized, placebo-controlled trial of NAC supplementation (2700 mg/d) to standard medications. Neurocognition was assessed at baseline and at the end of treatment with the MATRICS Consensus Cognitive Battery (MCCB),6 excluding the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Sixty-one patients (31 NAC, 30 placebo) with a diagnostic of psychotic disorder and less than 12 months of antipsychotic treatment were enrolled. Results: We found significant interaction Time × Treatment in favor of NAC on the MCCB processing speed factor and for 2 of 3 processing speed’s tasks (Trail Making A and Verbal Fluency). The improvement in processing speed within the NAC group was correlated with a decrease in negative symptoms. In addition, it was possible to identify a subgroup of patients who responded to NAC treatment considering their biological variables. Indeed, patients having a low peroxidase (GPx) activity at baseline benefited more than others from NAC supplementation in terms of processing speed’s scores. Moreover, in those individuals only, the improvement in processing speed was related to a decrease of the GSH reductase (GR) activity and to a regulation of the balance GPx – GR. Conclusion: Addition of NAC improved processing speed in EP patients, in particular in those who displayed a low basal level of redox dysregulation. Further, larger studies on antioxidant interventions are needed to replicate these findings. This work was supported by the National Center of Competence in Research (NCCR) “SYNAPSY – The Synaptic Bases of Mental Diseases” financed by the Swiss National Science Foundation, Damm-Etienne Foundation, Alamaya Foundation, the Commonwealth of Massachusetts Center of Excellence in Clinical Neuroscience and Psychopharmacological Research (SCDMH82101008006, LJS), and the Weisman family (LJS). References 1.Mesholam-Gately et al. Neuropsychology. 2009;23(3). 2.Green et al. Schizophrenia Bulletin. 2000;26(1). 3.Do et al. Current Opinion in Neurobiology. 2009;19(2). 4.Do et al. European Journal of Neuroscience. 2000;12(10). 5.Berk et al. Journal of Biological Psychiatry. 2008;64. 6.Nuechterlein et al. American Journal of Psychiatry. 2008;165.