This is a parallel-group, placebo-controlled trial examining the cognitive effects at weeks 1, 4, & 8 of once-weekly oral D-cycloserine 50 mg added to a stable dose of antipsychotic for 8 weeks in adult outpatients with schizophrenia.

In a previous placebo-controlled trial, investigators demonstrated significant improvement of negative symptoms with once-weekly D-cycloserine treatment. In addition, investigators 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, investigators propose to administer the Logical Memory Test at four-week intervals (weeks 1, 4 and 8) to avoid the ceiling effect. Additionally a measurement will be added 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.

Inclusion Criteria:

1. Male or female
2. Age 18-65 years
3. Diagnosis of schizophrenia or schizoaffective disorder, depressed type
4. Stable dose of antipsychotic for at least 4 weeks.
5. Able to provide informed consent
6. Able to complete a cognitive battery

Exclusion Criteria:

1. Current treatment with clozapine
2. Dementia
3. Seizure disorder
4. Unstable medical illness
5. Active substance abuse
6. Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile.
7. Severe renal insufficiency (Serum creatinine > 1.5 mg/dL)