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 2,376 individuals (465 MDD, 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 schizophrenia-in particular, in a subgroup of patients with schizophrenia with a lifetime history of depressive symptoms.
Schumacher
Johannes
J
Institute of Human Genetics, University of Bonn, Bonn.
Jamra
Rami Abou
RA
Becker
Tim
T
Ohlraun
Stephanie
S
Klopp
Norman
N
Binder
Elisabeth B
EB
Schulze
Thomas G
TG
Deschner
Monika
M
Schmäl
Christine
C
Höfels
Susanne
S
Zobel
Astrid
A
Illig
Thomas
T
Propping
Peter
P
Holsboer
Florian
F
Rietschel
Marcella
M
Nöthen
Markus M
MM
Cichon
Sven
S
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D018900:Dinucleotide Repeats; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor