Altered levels of Reelin and its isoforms in schizophrenia and mood disorders

Reelin is a secreted extracellular matrix protein similar to 410 kDa mol. w t that is reduced in brains of patients with schizophrenia, autism, bipolar disorder and major depression. Recent reports also indicate its near absen ce in sera of some patients with an autosomal recessive form of lissencepha ly. Moreover, Reelin is involved not only in normal cortical lamination of the brain during mammalian embryogenesis but is also implicated in cell sig naling systems subserving cognition in adult brain. Here, we show that bloo d levels of Reelin and its isoforms are altered in three psychiatric disord ers, namely, schizophrenia, bipolar disorder and major depression. The chan ges include significant increases in 410kDa. Reelin moiety of 49% in schizo phrenic patients (p<0.022) of four ethnic compositions (Caucasian, Vietname se, Hmong and Laotian) and non-significant increases in depressed patients by 34% vs control blood. In contrast, 410 kDa Reelin levels decreased by 33 % in bipolar blood, albeit non-significantly, vs controls. There was a sign ificant increase of 90% (p<0.0061) in 330 kDa Reelin in Caucasian schizophr enics; the depressed value was elevated by 30% vs control but non-significa ntly. Again, in contrast, bipolar 330 kDa value decreased by 31% vs control (p<0.0480). Finally, all 180 kDa Reelin values varied minimally in schizop hrenics vs controls. In contrast, the 180 kDa Reelin values dropped signifi cantly by 49% (p<0.0117) and 29% (p<0.0424) in bipolar and depressed patien ts, respectively, compared with controls. The alterations in blood Reelin v alues appear to be specific since levels of two other blood proteins, cerul oplasmin and albumin did not vary significantly between all psychiatric sub jects 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 t herapeutic interventions. NeuroReport 12:3209-3215 (C) 2001 Lippincott Will iams & Wilkins.