IEPA 11

Alan Breier1,2,3, Jenifer Vohs1,2,3, Bethany Leonhardt1,2,3, Nicole Mehdiyoun1,2, Tom Hummer1,2, Emily Liffick1,2,3,4, Michael Francis1,2,3; 1Department of Psychiatry, Indiana University School of Medicine, 2Indiana University Psychotic Disorders Program, IUSM, 3Eskenazi Health Midtown Community Mental Health Center, 4Eli Lilly and Company
               
Background: Negative and cognitive symptoms are core features of schizophrenia and contribute to the marked functional deficits and poor quality of life associated with this illness. Currently approved medications for schizophrenia, however, are relatively ineffective for these symptom domains. N-Acetyl Cysteine (NAC) is a neuroprotective agent that mitigates the deleterious effects of oxidative stress, inflammation and glutamatergic toxicity. Because of its unique mechanisms of action, NAC has been investigated in several clinical trials in schizophrenia. While there is agreement that NAC appears ineffective for positive symptoms, the outcomes data for negative symptoms and cognitive impairment are conflicting. Methods: In this paper, we assessed the effects NAC (3600 mg/day) in a 52-week, double-blind, placebo controlled trial in early phase schizophrenia spectrum disorders (N=60). Results: NAC significantly improved (time x group) PANSS negative symptoms (F=5.1, p=0.024), as well as PANSS total (F=14.7, p<0.001) and disorganized thought (F=13.7, p<0.001) symptom scores. NAC failed to improve BACS cognitive total composite and individual cognitive test scores, as well as PANSS positive symptom scores. Baseline right (r= -0.48, p=0.041) and left (r= -0.45, p=0.018) total cortical thickness, and thickness in other cortical regions, were associated with NAC related improvement in symptom scores. Conclusions: These results replicate some but not all previous findings of NAC efficacy. The discrepancies among NAC studies for negative and cognitive symptom results will be addressed with suggestions to reconcile these differences.