This suggests that the first step in pathogenesis, in NMO and other in autoantibody-mediated CNS diseases, is BBB disruption: in the case of NMO due either to antibodies directed against AQP4 within the BBB43 or to induction of IL-6 production by AQP4-positive astrocytes.44 This disruption may allow leakage of AQP4 antibodies into the cerebrospinal fluid (CSF).45 We have reviewed the implications of BBB dysregulation in psychosis elsewhere.46 This evidence concerns the gene IL6 and neuromyelitis optica.