• SANS
• Renal - creatanine
• Renal - urinalysis

• Positive and Negative Symptoms Scale (PANSS) [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
• Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
• Clinical Global Impression (CGI) [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]

• Total PANSS
• PANSS positive
• PANSS cognitive
• Neuropsychological - MATRICS battery

This study will determine whether increasing D-serine within the body will improve negative symptoms and cognitive impairments in people with schizophrenia.

Schizophrenia is a life-long brain disorder affecting approximately 1 percent of Americans each year. Schizophrenia can be extremely disabling, causing people to hear voices, experience paranoia or hallucinations, believe that others are controlling their thoughts, and even fail at maintaining a job or caring for themselves. Current medications help to relieve most of these symptoms, but not all. Some people with schizophrenia still suffer from negative symptoms, such as difficulty with talking, expressing emotions, and motivation; they may also suffer from cognitive impairments, such as decreased concentration and memory loss. D-serine, an amino acid found within the body, activates brain cell receptors that appear to play a role in learning and memory. This study will determine whether adding a D-serine solution to a stable antipsychotic medication regimen will decrease negative symptoms in people with schizophrenia.

Participants in this open-label study will remain on their regular medication regimen for at least 2 weeks. During this time and before starting treatment, participants will be interviewed about their emotional problems, marital status, education, family background, employment history, and any drug or alcohol problems. Participants will also undergo a physical exam, an electrocardiogram (EKG), vital sign measurements, psychological tests, cognitive tasks, and an electroencephalogram (EEG). Participants will then begin 4 weeks of treatment with D-serine. In addition to participants' regular medication regimen, they will drink a D-serine powder mixed with water twice daily. Every 2 weeks, participants will undergo a physical exam and an interview about any changes in symptoms or emotional problems that they may be experiencing. Blood and urine samples will be taken throughout the study. After 4 weeks, participants will undergo an EKG, EEG, and the same psychological tests and cognitive tasks completed prior to treatment. A follow-up visit will occur 2 weeks post-treatment to monitor any changes in negative symptoms.

Inclusion Criteria:

• Structured Clinical Interview for DSM-III-R diagnosis of schizophrenia or schizoaffective disorder
• PANSS 3 factor negative symptom inclusion score greater than 20 prior to study entry
• PANSS total score between 60 and 110
• Simpson-Angus Scale total score of 12 or less
• Calgary Depression Inventory total score of 10 and suicide score less than 2
• No change in Clinical Global Impressions (CGI) Scale score prior to study entry
• Chlorpromazine (CPZ) equivalent of 1500 or less
• Willing to use an effective form of birth control throughout the study if sexually active

Exclusion Criteria:

• High extrapyramidal symptom (EPS) levels
• Began, discontinued, or adjusted psychotropic medication within 2 weeks of study entry
• Taking investigational medication within 2 weeks of study entry
• Contraindication to study medication
• Serious or unstable medical illness
• Pregnant or breastfeeding
• Alcohol or drug abuse within 6 months of study entry
• Diagnosed with neurodegenerative disease or a seizure disorder
• History of a kidney impairment
• Currently taking clozapine
• Currently taking more than two antipsychotic medications
• Currently taking stimulants or cholinesterase inhibitors