OBJECTIVES: Evidence has accumulated that an autoimmune-mediated process in the central nervous system may underlie the development of schizophrenia. Various antibodies have also previously been detected in serum of patients with schizophrenia. Therefore, the aim of this study was to analyze antibody reactivity against proteins, selected based on potential schizophrenia disease relevance, in both cerebrospinal fluid and serum of patients with schizophrenia. MATERIAL AND METHODS: Cerebrospinal fluid and serum from 17 patients with schizophrenia or related psychosis and 12 controls were analyzed regarding antibody reactivity, using bead-based antigen arrays of protein fragments or peptides of 21 selected proteins. Additionally, the patients were accessed for clinical symptoms with the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. RESULTS: Increased antibody reactivity was found in patients compared to controls against the insulin receptor (INSR), PAGE2B;2;5 and heat shock proteins (HSPs) in both cerebrospinal fluid and serum, and against the insulin like growth factor 1 receptor (IGF1R), insulin (INS), insulin like growth factor 1 (IGF1), cadherin 5 (CDH5), nerve growth factor (NGF) and vascular endothelial growth factor A (VEGFA) in serum alone. Moreover, patients' antibody reactivity in serum against PAGE2B;2;5, IGF1R or NGF correlated positively to their PANSS scores. CONCLUSIONS: Taken together, these results point to that an autoimmune-mediated process underlies the development of a core group of schizophrenia cases and that the INSR and IGF1R, their ligands (INS and IGF1) and related inter- and intracellular proteins (CDH5, PAGE2B;2;5, HSPs, NGF and VEGFA) may constitute antigen targets.