A Placebo-Controlled Study of Physiologic Effects of L-methylfolate in Schizophrenia Patients

Inclusion Criteria: * Diagnosis of schizophrenia, any subtype * Male of female * Age 18-68 years * Treated with an antipsychotic for at least 6 months at a stable dose for at least 6 weeks * PANSS total score of at least 60, with at least 3 (moderate) on one negative symptom item or on one positive symptom item * Simpson Angus Scale (SAS) for the EPS total score of 12 or less and * A score of 2 (mild) or less on all items of the Calgary Depression Rating Scale (CDRS) * Comprehension of English adequate to complete cognitive testing Exclusion Criteria: * Unable to provide informed consent * CBC results consistent with megaloblastic anemia * Serum creatinine concentration greater than 1.4 * Current use of folate supplementation \> 400mcg folate * Alcohol or other substance abuse within 3 months (nicotine allowed) * Current use of any of the following medications: phenobarbital, phenytoin, carbamazepine, valproic acid, fosphenytoin, primidone or pyrimethamine * Positive baseline urine toxic screen, (positive test for PCP, barbiturates, cannabinoids, amphetamines, benzodiazepines, opiates, or cocaine) * Unstable medical illness (exclusionary lab values are listed in Appendix A) * Unstable psychiatric illness * Seizure disorder * Pregnant or nursing, or planning/trying to get pregnant within the next 6 months, and * DSM-IV diagnosis of major depressive disorder