Anti-Inflammatory Challenge in Schizophrenia

Inclusion Criteria: Men or women, 18-45 years of age with a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders (DSM-V) schizophrenia or schizoaffective disorder; Willing and able to give written informed consent; Plasma CRP 3mg/L; Significant motivational deficit as reflected by a score >17 on the Motivation and Pleasure Domain of the Brief Negative Symptom Scale. Of note, for patients who exhibit CRP>10mg/L, additional CRP testing will be conducted at 2-week intervals as per American Heart association/ Center for Disease and Control Prevention guidelines to establish stability and rule out acute inflammation/infection (along with physical exam and laboratory testing). Subjects may be taking psychotropic medications at the time of the study (including antipsychotics, antidepressants, mood stabilizers, benzodiazepines) but may have no psychotropic medication changes for one month prior to study enrollment. Patients must also have a negative urine drug screen at all study visits. Exclusion Criteria: Any autoimmune disorder (as confirmed by laboratory testing); History of tuberculosis infection as determined by QuantiFERON Gold or high risk of tuberculosis exposure; Active hepatitis B or C infection or human immunodeficiency virus infection (as established by laboratory testing); History of any type of cancer; History of fungal infection; History of recurrent viral or bacterial infections; Unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurological disease (as determined by physical examination and laboratory testing); Demyelinating brain disease and/or a concerning structural abnormality seen on MRI; Substance abuse/dependence within 6 months of study entry (as determined by MINI and urine drug screen); Primary diagnosis of mood or anxiety disorder (i.e., major depressive disorder, bipolar disorder, post-traumatic stress disorder) as determined by International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders (MINI). Active suicidal ideation or plan; An active eating disorder; A history of cognitive disorder or Mini-Mental State Exam < 24 (indicating cognitive impairment); Pregnancy or lactation; Treatment with clozapine (given increased risk of neutropenia/agranulocytosis); Women of child bearing potential who are not using a medically accepted means of contraception; Known allergy to murine products or other biologic therapies; Previous organ transplant; Administration of any modified live virus vaccine within one month of study entry, during the study and for at least one month after the final study visit; Oral glucocorticoids, immunosuppressive drugs (e.g. anti-cytokine therapies or methotrexate) or any other drugs targeting the immune system within 6 months of baseline; Chronic use of non-steroidal anti-inflammatory agents (NSAIDS; excluding 81mg of aspirin), glucocorticoid containing medications or minocycline or non-prescription supplements with known or suspected anti-inflammatory properties (e.g. fish oil supplements, curcumin, pre- or probiotics) within 2 weeks of baseline or at any time during the study; Use of non-steroidal anti-inflammatory agents (NSAIDS), glucocorticoid containing medications at any time during the study; Any contraindication to MRI. Due to the high co-morbidity between schizophrenia and mood/anxiety disorders, the study team plans to include patients with these diagnoses as long as schizophrenia is the primary diagnosis. Subjects may be taking psychotropic medications at the time of the study (including antipsychotics, antidepressants, mood stabilizers, benzodiazepines) but may have no psychotropic medication changes for one month prior to study enrollment or during participation in the study. Patients with stable medical conditions and on medications for those conditions will not be excluded. No patient will be removed from antipsychotic treatment for the purposes of this study.