Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression

Accumulation of neurobiological knowledge points to neurodevelopmental orig ins for certain psychotic and mood disorders. Recent landmark postmortem re ports implicate Reelin, a secretory glycoprotein responsible for normal lam ination of brain, in the pathology of schizophrenia and bipolar disorders. We employed quantitative immunocytochemistry to measure levels of Reelin pr otein in various compartments of hippocampal formation in subjects diagnose d with schizophrenia, bipolar disorder and major depression compared to nor mal controls. Significant reductions were observed in Reelin-positive adjus ted cell densities in the dentate molecular layer (ANOVA, P < 0.001), CA4 a rea (ANOVA, P < 0.001), total hippocampal area (ANOVA, P < 0.038) and in Re elin-positive cell counts in CA4 (ANOVA, P < 0.042) of schizophrenics vs co ntrols. Adjusted Reelin-positive cell densities were also reduced in CA4 ar eas of subjects with bipolar disorder (ANOVA, P < 0.001) and nonsignificant ly in those with major depression. CA4 areas were also significantly reduce d in schizophrenic (ANOVA, P < 0.009) patients. No significant effects of c onfounding variables were found. The exception was that family history of p sychiatric illness correlated strongly with Reelin reductions in several ar eas of hippocampus (CA4, adjusted cell density, F = 13.77, P = 0.001), We p resent new immunocytochemical evidence showing reductions in Reelin express ion in hippocampus of subjects with schizophrenia, bipolar disorder and maj or depression and confirm recent reports documenting a similar deficit invo lving Reelin expression in brains of subjects with schizophrenia and bipola r disorder.