ALTERED LEVELS OF REELIN AND ITS
ISOFORMS IN SCHIZOPHRENIA AND MOOD DISORDERS
SH Fatemi, University of Minnesota
Reelin is a secreted extracellular
matrix protein ~410kDa mol wt that is reduced in brains of patients with
schizophrenia, autism, bipolar disorder and major depression. Recent
reports also indicate its near absence in sera of some patients with an
autosomal recessive form of lissencephaly. Moreover, Reelin is involved
not only in normal cortical lamination of the brain during mammalian
embryogenesis, but is also implicated in cell signaling systems subserving
cognition in adult brain. Here, we show that blood levels of Reelin and
its isoforms are altered in three psychiatric disorders, namely, schizophrenia,
bipolar disorder and major depression. The changes include significant
increases in 410kDa Reelin moiety of 49% in schizophrenia patients (p<0.022) of four ethnic compositions (Caucasians, Vietnamese, Hmong and Laotian) and non-significant increases in depressed patients by 34% vs control blood. In contrast, 410kDa Reelin levels decreased by 33% in bipolar blood, albeit non-significantly, vs. controls. There was a significant increase of 90% (p<0.006) in 330 kDa Reelin in Caucasian schizophrenics; the depressed value was elevated by 30% vs control but non-significantly. Again, in contrast, bipolar 330 kDa value decreased 31% vs control (p<0.0480). Finally, all 180 kDa Reelin values varied minimally in schizophrenics vs controls. In contrast, the 180 kDa Reelin values dropped significantly by 49% (p<0.0117) and 29% (p<0.0424) in bipolar and depressed patients, respectively, compared with controls. The alterations in blood Reelin values appear to be specific since levels of two other blood proteins, ceruloplasmin and albumin did not vary significantly between all psychiatric subjects and controls. These findings suggest that blood Reelin levels and its isoforms may be used as potential peripheral markers to diagnose presence of several psychiatric disorders and may also serve as targets for future therapeutic interventions.