Antibody reactivity in cerebrospinal fluid and serum against the insulin-insulin-like growth factor 2 (INS-IGF2) protein is associated with psychotic symptomatology in patients with schizophrenia or related psychosis.

Objectives: Evidence has accumulated that an autoimmune-mediated process may underlie development of schizophrenia, and in two recent studies, we found increased antibody reactivity against the insulin receptor-A (INSR-A) and insulin-like growth factor 1 receptor (IGF1R) and their ligands (insulin and insulin-like growth factor 1) in cerebrospinal fluid (CSF) and/ or serum from patients with schizophrenia or related psychosis. The aim of this study was to analyze antibody reactivity in schizophrenia against the insulin-insulin-like growth factor 2 (INS-IGF2) protein, which hypothetically also may be a ligand to INSR-A and IGF1R and involved in the pathogenesis of schizophrenia.

Material and methods: Patients with schizophrenia or related psychosis and controls were analyzed regarding antibody reactivity against INS-IGF2 in CSF (n = 12/ n = 11) and serum (n = 17/ n = 11), using bead-based antigen arrays of one protein fragment and 24 peptides of this protein. Additionally, the patients were assessed for clinical symptoms with the Positive and Negative Syndrome Scale (PANSS) for schizophrenia.

Results: Significantly higher antibody reactivity against the peptides 11 and 12 was found in patients in partial than full symptom remission. Patients' antibody reactivity against the peptides 5, 11 and 12 correlated positively to their PANSS scores of positive symptoms. Furthermore, significantly higher antibody reactivity against the peptides 2, 3, 10 and 22 was found in patients with, than without, heredity for diabetes mellitus type 1 or 2.

Conclusion: The findings in this study pointed that the INS-IGF2 protein may be present in the CNS and involved in the autoimmune-mediated process underlying the development of schizophrenia.