OBJECTIVE: The authors conducted a dose-finding study of D-cycloserine,
a partial agonist at the glycine site of the N-methyl-D-aspartate subtype
of the glutamate receptor, added to conventional neuroleptics for
schizophrenic patients with prominent negative symptoms. METHOD: Nine
patients with schizophrenia completed consecutive 2-week trials of placebo
and four doses of D-cycloserine. Clinical assessments were videotaped and
were scored by a rater who was blind to temporal sequence. RESULTS:
D-Cycloserine at a dose of 50 mg/day produced a significant reduction (mean
= 21%, SD = 28%) in negative symptoms and significantly improved reaction
time as measured by Sternberg's Item Recognition Paradigm, a test mediated
in part by prefrontal cortex. CONCLUSIONS: This preliminary evidence
suggests that D-cycloserine may improve negative symptoms and cognitive
deficits over a narrow dose range when added to conventional antipsychotic
agents.Abstract Teaser