Fingolimod in Schizophrenia Patients

Inclusion * 18 to 65 yrs, able to give informed consent * DSM IV-TR Diagnosis of schizophrenia or schizoaffective disorder * Previous and/or current exposure to one of the following antipsychotic medications (clozapine, olanzapine, risperidone, paliperidone, haloperidol, quetiapine) as defined by a minimum of 8 weeks in duration greater than or equal to the Food and Drug Administration (FDA) approved therapeutic range for schizophrenia at the time of study entry OR previous and/or current exposure to two antipsychotic medications as defined by a minimum of 4 weeks in duration and greater than or equal to the FDA approved therapeutic range for schizophrenia at the time of study entry * willing to participate in a minimum of 1 day of hospitalization * Clinical stability: 1. CGI-S score of \< 4 at randomization AND 2. no exacerbation of illness within 4 weeks prior to randomization, leading to an intensification of psychiatric care in the opinion of the investigator AND 3. antipsychotic treatment stability for at least 4 weeks prior to randomization * Female subjects of childbearing potential must test negative for pregnancy at screening and agree to use a single, effective, medically acceptable method of birth control for the duration of the study and for two months following cessation of study medication * Subjects must agree not to consume tonic water for the duration of the study and for two months following cessation of study medication * Sub-optimally treated positive OR negative symptoms as defined by the Brief Psychiatric Rating Scale (BPRS): 1. BPRS positive symptom factor (conceptual disorganization, hallucinations, suspiciousness, unusual thought content) score of \> 4 on any one item or a sum \> 8 on the factor 2. BPRS negative symptom factor (motor retardation, blunted affect, inappropriate affect) score of \> 4 on any one item or a sum \> 6 on the factor Exclusion * Subjects who are considered prisoners per the IU Standard Operating Procedures for Research Involving Human Subjects * Current acute, serious, or unstable medical conditions * Clinically significant electrocardiogram abnormality: corrected QT interval \>450 msec (M) or \>470 msec (F) prior to randomization OR sinus bradycardia (HR \< 50 beats/min) * Subjects who have experienced the following within the six months prior to study entry: myocardial infarction, unstable angina, stroke, transient ischemic attach (TIA), decompensated heart failure requiring hospitalization or Class III/IV heart failure * Hypokalemia, hypomagnesemia, or congenital long-QT syndrome * Known HIV+ status * Active seizure disorder * Pregnant or lactating women or women who plan to become pregnant or will be lactating within two months after cessation of study drug * Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, ventriculoperitoneal shunt, or other contraindication to undergoing an MRI scan * Class1a or class 3 antiarrhythmic agents, beta blockers, diltiazem, verapamil, digoxin, tricyclic antidepressants, warfarin, ketoconazole, ketamine * Subjects likely to need a live attenuated vaccine during the course of the study or within two months after stopping study medication * Subjects with no history of chicken pox or chicken pox vaccination, or with a negative VZV titer * Active herpes simplex outbreak, mononucleosis, or zoster * Subjects with histories of ischemic heart disease, myocardial infarction, congestive heart failure, cardiac arrest, cerebrovascular disease, unexplained or recurrent syncope, cardiac conduction prolongations (prolonged P-R interval), cardiac arrhythmias, symptomatic bradycardia, or severe untreated sleep apnea * Antineoplastic, immunosuppressive, or immune modulating therapies * History of macular edema or uveitis * Known IQ \< 70 * Current active fungal or viral infection * Current DSM IV-TR diagnosis of substance dependence (excluding caffeine and nicotine) * Positive urine toxicology screen for the following: cocaine, barbiturates, methamphetamine, opiate, methadone, phencyclidine, or amphetamine prior to randomization * Test positive for (1) Hep C virus antibody, (2) Hep B surface antigen (HBsAg) with or without positive Hep B core total antibody, (3) HIV 1 or 2 antibodies, or (4) Mantoux tuberculin test. * Moderate to severe renal impairment as defined by creatinine clearance \< 60 ml/min at screening * Hepatic impairment as defined by liver transaminases or total bilirubin \> 3 × upper limit of normal * Subjects considered a high risk for suicidal acts - active suicidal ideation OR any suicide attempt in 90 days prior to screening * Subjects who have participated in a clinical trial with any pharmacological treatment intervention for which they received study-related medication in the 4 weeks prior to screening OR Subjects currently receiving treatment (within 1 dosing interval + 4 weeks) with an investigational depot formulation of an antipsychotic medication * Subjects who demonstrate overtly aggressive behavior or who are deemed to pose a homicidal risk in the investigator's opinion