Evidence for a Relationship Between Genetic Variants at the Brain-Derived Neurotrophic Factor (BDNF) Locus and Major Depression

• Published in: Biological psychiatry (1969) 2005-08, Vol.58 (4), p.307-314
• Main Authors: Schumacher, Johannes, Jamra, Rami Abou, Becker, Tim, Ohlraun, Stephanie, Klopp, Norman, Binder, Elisabeth B., Schulze, Thomas G., Deschner, Monika, Schmäl, Christine, Höfels, Susanne, Zobel, Astrid, Illig, Thomas, Propping, Peter, Holsboer, Florian, Rietschel, Marcella, Nöthen, Markus M., Cichon, Sven
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Association; BDNF; Biological and medical sciences; bipolar affective disorder; Bipolar Disorder - genetics; Bipolar disorders; Brain-Derived Neurotrophic Factor - genetics; Case-Control Studies; Depression; Depressive Disorder, Major - genetics; Dinucleotide Repeats; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation - genetics; Genotype; haplotype analysis; Humans; Male; Medical sciences; Middle Aged; Mood disorders; Polymorphism, Genetic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - genetics; unipolar depression
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2005.04.006

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. We performed single-marker and haplotype analyses using three BDNF polymorphisms in 2,376 individuals (465 MDD, 281 BPAD, 533 schizophrenia, and 1,097 control subjects). 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. 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 schizophrenia—in particular, in a subgroup of patients with schizophrenia with a lifetime history of depressive symptoms.