RELN and schizophrenia: During the second half of the 1990s, a series of reports from the laboratory of Drs. Erminio Costa and Alessandro Guidotti (University of Illinois at Chicago) provided the first demonstrations that the extracellular matrix protein reelin was heavily downregulated (about 50%) in multiple brain areas from schizophrenia post-mortem brain samples (Impagnatiello et al., 1998) and in the cerebral cortex of bipolar patients with psychotic episodes (Guidotti et al., 2000).