Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression

Background- Previous genetic studies investigating a possible involvement of variations at the brain derived neurotrophic factor (BDNF) gene locus in major depressive disorder (MDD), bipolar affective disorder (BPAD), and schizophrenia have provided inconsistent results. Methods: We performed single-marker and haplotype analyses using three BDNF-polymorphisms in 2,3 76 individuals (465MDD, 281 BPAD, 533 schizophrenia, and 1, 097 control subjects), Results. Single-marker analysis did not provide strong evidence for association. Haplotype analysis of marker combination rs988748-(GT)(n)-rs6265 produced nominally significant associations for all investigated phenotypes (global p values: MDD p =.00006, BPAD p = 0057, schizophrenia p =.016). Association with MDD was the most robust finding and could be replicated in a second German sample of MDD patients and control subjects (p =.0092, uncorrected). Stratification of our schizophrenia sample according to the presence or absence of a lifetime history of depressive symptoms showed that our finding in schizophrenia might be attributable mainly to the presence of depressive symptoms. Conclusions: Association studies of genetic variants of the BDNF gene with various psychiatric disorders have been published with reports of associations and nonreplications. Our findings suggest that BDNF may be a susceptibility gene for MDD and schizopbrenia-in particular, in a subgroup of patients with schizophrenia with a lifetime history of depressive symptoms.