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

2012-12
Schizophrenia research 142(1-3)
- K N Roy Chengappa
- Scott R Turkin
- Susan DeSanti
- Christopher R Bowie
- Jaspreet S Brar
- Patricia J Schlicht
- Sherry L Murphy
- Michelle L Hetrick
- Robert Bilder
- David Fleet

PubMed: 23099060
DOI: 10.1016/j.schres.2012.10.001

Study Design

Type: Randomized Controlled Trial (RCT)
Population: 75 symptomatically stable adults with chronic schizophrenia
Methods: Randomly assigned to L-carnosine as adjunctive treatment (2 g/day) or matched placebo in a double-blind manner for 3 months
Blinding: Double-blind
Duration: 3 months

Background

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.

Methods

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.

Results

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.

Conclusions

These preliminary findings suggest that L-carnosine merits further consideration as adjunctive treatment to improve executive dysfunction in persons with schizophrenia.

Research Insights

L-Carnosine→Improved Attention Span
Other cognitive tests showed no significant differences between treatments
Effect
Neutral
Effect size
Small
Dose
2 g/day
L-Carnosine→Improved Cognitive Flexibility
reversal reaction times and errors were not significantly different between treatments
Effect
Neutral
Effect size
Small
Dose
2 g/day
L-Carnosine→Improved Memory Function
Other cognitive tests showed no significant differences between treatments
Effect
Neutral
Effect size
Small
Dose
2 g/day
L-Carnosine→Improved Motor Speed
Other cognitive tests showed no significant differences between treatments
Effect
Neutral
Effect size
Small
Dose
2 g/day
L-Carnosine→Improved Set-Shifting
reversal reaction times ... were not significantly different between treatments
Effect
Neutral
Effect size
Small
Dose
2 g/day
L-Carnosine→Improved Set-Shifting Reaction Time
The L-carnosine group performed significantly faster on non-reversal condition trials of the set-shifting test compared with placebo
Effect
Beneficial
Effect size
Small
Dose
2 g/day
L-Carnosine→Improved Strategic Efficiency
the L-carnosine group displayed significantly improved strategic efficiency and made fewer perseverative errors compared with placebo
Effect
Beneficial
Effect size
Small
Dose
2 g/day
L-Carnosine→Reduced Perseverative Error
the L-carnosine group displayed significantly improved strategic efficiency and made fewer perseverative errors compared with placebo
Effect
Beneficial
Effect size
Small
Dose
2 g/day
L-Carnosine→Reduced Perseverative Errors
the L-carnosine group ... made fewer perseverative errors compared with placebo
Effect
Beneficial
Effect size
Small
Dose
2 g/day
L-Carnosine→Reduced Psychopathology Symptoms
Psychopathology scores remained stable
Effect
Neutral
Effect size
Small
Dose
2 g/day
L-Carnosine→Reduced Set-Shifting Reversal Error
reversal ... errors were not significantly different between treatments
Effect
Neutral
Effect size
Small
Dose
2 g/day

Adverse Events Reported

L-Carnosine→Overall tolerability
The carnosine group reported more adverse events (30%) compared with the placebo group (14%).
Finding
Increased risk
Magnitude
30% vs 14%
L-Carnosine→laboratory indices
Laboratory indices remained within acceptable ranges.
Finding
Reported