COMMENTARY Immunologic Therapeutics and Psychotic Disorders Edward T. Bullmore and Mary-Ellen Lynall From the Behavioural & Clinical Neuroscience Institute (EB, M-EL), Department of Psychiatry, University of Cambridge, Cambridge; ImmunoPsychiatry (EB), Alternative Discovery & Development, GlaxoSmithKline, Stevenage; and Cambridgeshire & Peterborough NHS Foundation Trust (EB), Cambridge, United Kingdom. Address correspondence to Edward T. Bullmore, M.B., Ph.D., Behavioural & Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, Herchel Smith Building for Brain & Mind Sciences, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; E-mail: etb23@cam.ac.uk. Received Dec 16, 2013; accepted Dec 17, 2013. http://dx.doi.org/10.1016/j.biopsych.2013.12.006 There are no new ideas under the sun of psychosis. The idea that immunologic treatments might be effective for psychotic disorders arguably dates back to the 1870s, when Rosenblium published a series of case reports linking psychotic states to febrile episodes of malarial infection. Wagner-Jauregg won a Nobel Prize 40 years later for showing that syphilitic psychosis could be treated by medical inoculation of malarial parasites (1). Although inoculation of malarial parasites is not a potential treatment for psychotic disorders in the 21st century, this history does remind us that the more recent increasing interest in inflammatory mechanisms and treatments of psychosis represents a return of attention to an old idea in medicine—and premedical folklore—rather than a fundamentally new idea. In this Commentary, we take another look at this idea from the contemporary perspective of a potential investor—public or private—in new immunologic treatments for psychotic disorders. We discuss three key questions such an investor might ask about the future prospects of immunotherapeutics for psychosis: 1) What is the reason to believe? 2) How will it be different this time? 3) What will success look like? What Is the Reason to Believe? There is now good scientific “reason to believe,” from many lines of enquiry, that immune or inflammatory mechanisms are implicated in the pathogenesis of psychotic symptoms (see research articles in this issue of Biological Psychiatry). However, the therapeutic implications are not yet known for certain. A meta-analysis of trial data from 264 patients showed that nonsteroidal anti-inflammatory drugs (celecoxib and aspirin) reduced positive and negative symptoms of schizophrenia when used as adjuncts to standard antipsychotic therapy (2). There have also been positive clinical data on the effects