A preliminary, randomized, double-blind, placebo-controlled trial of L-carnosine to improve cognition in schizophrenia.

Targeting glutamatergic dysfunction provides an exciting opportunity to improve cognitive impairment in schizophrenia. One treatment approach has targeted inadequate antioxidant defenses at glutamatergic synapses. Animal and human data suggest NMDA antagonists worsen executive cognitive controls--e.g. increase perseverative responses and impair set-shifting. We conducted a preliminary study to test the hypothesis that L-carnosine, an antioxidant and anti-glycation agent which is co-localized and released with glutamate would improve executive dysfunction, a cognitive domain associated with glutamate. Seventy-five symptomatically stable adults with chronic schizophrenia were randomly assigned to L-carnosine as adjunctive treatment (2 g/day) or a matched placebo in a double-blind manner for 3 months. Cognitive domains (executive dysfunction, memory, attention and motor speed) were assessed using a computerized battery at baseline, 4 and 12 weeks, along with psychopathology ratings and safety parameters. The L-carnosine group performed significantly faster on non-reversal condition trials of the set-shifting test compared with placebo but reversal reaction times and errors were not significantly different between treatments. On the strategic target detection test, the L-carnosine group displayed significantly improved strategic efficiency and made fewer perseverative errors compared with placebo. Other cognitive tests showed no significant differences between treatments. Psychopathology scores remained stable. The carnosine group reported more adverse events (30%) compared with the placebo group (14%). Laboratory indices remained within acceptable ranges. These preliminary findings suggest that L-carnosine merits further consideration as adjunctive treatment to improve executive dysfunction in persons with schizophrenia.