Pregnenolone for Cognitive and Negative Symptoms in Schizophrenia

Inclusion Criteria: * Diagnosis: DSM-IV/DSM-IV TR schizophrenia or schizoaffective disorder; * Gender: Males and Females; * Age: 21-65; * Caucasian or Non Caucasian; * Capable of providing informed consent; * Duration of illness equal to or greater than one year; * No change in antipsychotic medication in the previous eight weeks, no change in antipsychotic dose in the previous four weeks; * No benzodiazepine use in the past twelve hours prior to cognitive testing; * The patient cohort will be enriched for cognitive symptoms (Composite BACS scores = 0-3 standard deviations below the mean, assessed at the screening visit). Exclusion Criteria: * Subjects with a DSM-IV/DSM-IV TR diagnosis of alcohol or substance dependence (other than nicotine) within the last month; * Subjects with a history of significant head injury/trauma, as defined by one or more of the following: * Loss of consciousness (LOC) for more than 1 hour, * Recurring seizures resulting from the head injury, * Clear cognitive sequelae of the injury, * Cognitive rehabilitation following the injury; * Subjects with unstable medical illness or neurological illness (seizures, CVA); * Patients with hormone-sensitive tumors (such as breast, uterine, or prostate cancer); * Clinically significant abnormalities in physical examination , ECG, or laboratory assessments; * Pregnant women or women of child-bearing potential, who are either not surgically-sterile or not using appropriate methods of birth control (serum beta-human chorionic gonadotropin \[HCG\] will be performed at baseline, 4 weeks, and 8 weeks to exclude pregnancy); * Women who are breast-feeding; * Electroconvulsive therapy (ECT) treatment within the last 3 months; * Use of oral contraceptives or other hormonal supplementation such as estrogen. Although early studies suggested no effects on menstrual cycle, alterations in downstream metabolites of pregnenolone (such as estradiol) could theoretically impact the efficacy of oral contraceptives and/or estrogen replacement. Similarly, it is theoretically possible that pregnenolone could be metabolized to other steroids, resulting in hair, skin, or other steroid-related changes. Since we have determined in our prior study that pregnenolone administration does not result in downstream elevations in DHEA, DHEAS, estradiol, or testosterone, these possibilities may be unlikely; * Current active suicidal and/or homicidal ideation, intent, or plan; * Known allergy to study medication.