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 significant degree, heritable. We therefore investigated brain derived neurotrophic factor (BDNF), a neurotrophin expressed in fetal brain, as a candidate disease gene for schizophrenia. We also investigated the effect of BDNF on adult brain morphology. All subjects were diagnosed by DSM-IIIR or DSM-IV criteria with schizophrenia spectrum disorders. Association of a BDNF polymorphism was examined in 48 proband-parent trios using the haplotype based haplotype relative risk method of case control. In a related group of 63 subjects, relationships between the presence or absence of allele 1 and the volumes of the major cerebral lobes, the ventricles, and the cerebellum were assessed using logistic regression. No association was found between this polymorphism and schizophrenia. Subjects who had at least one copy of allele 1, however, had larger parietal lobes than those who did not when controlling 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.