Heritability of BDNF alleles and their effect on brain morphology in schizophrenia

Accumulating evidence suggests that disturbed brain development may play a role in the etiology of schizophrenia, and that the illness is, to a signif icant degree, heritable. We therefore investigated brain derived neurotroph ic factor (BDNF), a neurotrophin expressed in fetal brain, as a candidate d isease gene for schizophrenia. We also investigated the effect of BDNF on a dult brain morphology, All subjects were diagnosed by DSM-IIIR or DSM-IV cr iteria with schizophrenia spectrum disorders, Association of a BDNF polymor phism was examined in 48 proband-parent trios using the haplotype based hap lotype relative risk method of case control. In a related group of 63 subje cts, relationships between the presence or absence of allele 1 and the volu mes of the major cerebral lobes, the ventricles, and the cerebellum were as sessed using logistic regression. No association was found between this pol ymorphism and schizophrenia. Subjects who had at least one copy of allele 1 , however, had larger parietal lobes than those who did not when controllin g for overall cortical volume and age at the time of magnetic resonance. We did not find support for BDNF as a disease gene for schizophrenia. Allelic variability of the gene may, however, influence brain morphology in these same subjects. Am. J. Med. Genet, (Neuropsychiatr, Genet,) 88:724-728, 1999 . (C) 1999 Wiley-Liss, Inc.