The dysbindin gene in major depression: an association study.
The pathophysiological mechanisms, as well as the molecular loci of antidepressant drug action have not yet been established, but recent models proposed that several adaptive mechanisms in signal transduction cascades beyond the receptor and reuptake systems are involved in antidepressant action and play an important role in the etiology of affective disorders. In this context, the dysbindin gene (dystrobrevin-binding-protein 1, DTNBP1), which was recently reported to be associated with schizophrenia seems to be an interesting candidate gene for affective disorders. Dysbindin is widely expressed in the human brain and binds to the dystrophin-associated protein complex (DPC) which appears to be involved in signal transduction pathways, which have been repeatedly investigated and described as altered or disturbed in affective disorders [McLeod et al. [2003: Psychopharmacol Bull 35:24-41]; Brambilla et al. [2003: Mol Psychiatry 8:721-737]]. Therefore, we investigated whether five SNPs in the dysbindin gene could be susceptibility factors in the ethiology of major depression or for the response to antidepressant treatment in a sample of 293 patients compared to 220 healthy controls. Applying single SNP evaluation, as well as haplotype analysis we could not detect an association between the dysbindin polymorphisms and major depression or the response to antidepressant treatment. In conclusion, our results suggest that SNPs in the dysbindin gene are unlikely to play a major role in the pathophysiology of major depression or are in linkage disequilibrium (LD) with a neighboring mutation or gene. Further analysis are needed to confirm these results.
Zill
Peter
P
Psychiatric Hospital of the Ludwig-Maximilians-University, Munich, Germany. Peter.Zill@psy.med.uni-muenchen.de
Baghai
Thomas C
TC
Engel
Rolf
R
Zwanzger
Peter
P
Schüle
Cornelius
C
Eser
Daniela
D
Behrens
Stefanie
S
Rupprecht
Rainer
R
Möller
Hans-Jürgen
HJ
Ackenheil
Manfred
M
Bondy
Brigitta
B
D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D003865:Major Depressive Disorder / Q000235:genetics*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D004247:DNA