Once Weekly D-cycloserine for Schizophrenia

In a previous placebo-controlled trial, we demonstrated significant improvement of negative
symptoms with once-weekly D-cycloserine treatment. In addition, we found significant
improvement of memory consolidation following the first dose; however, the effect on memory
consolidation was lost after several weeks. The "practice effect" of weekly measurement of
memory consolidation using repeated administration of the Logical Memory Test may have
resulted in a "ceiling effect" which would obscure drug/placebo differences. In the current
study, we propose to administer the Logical Memory Test at four-week intervals (weeks 1, 4
and 8) to avoid the ceiling effect. We will also add a measurement of negative symptoms at
week 4 to better characterize the time course of negative symptom improvement.

Hypotheses:

1. Assess the effects of a single dose of D-cycloserine 50 mg on memory consolidation as
measured by the Logical Memory Test compared to placebo.

2. Assess the persistence of once-weekly D-cycloserine effects on memory consolidation
measured at weeks 4 & 8.

3. Assess the effects of repeated weekly dosing of D-cycloserine on performance on a
standard cognitive battery at week 8 compared to placebo.

4. Assess effects of weekly D-cycloserine dosing on negative symptoms at weeks 4 & 8
compared to placebo.

5. Assess tolerability and side effects of weekly D-cycloserine compared to placebo.