Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression.
The clinical efficacy of a systemically administered drug acting on the central nervous system depends on its ability to pass the blood-brain barrier, which is regulated by transporter molecules such as ABCB1 (MDR1). Here we report that polymorphisms in the ABCB1 gene predict the response to antidepressant treatment in those depressed patients receiving drugs that have been identified as substrates of ABCB1 using abcb1ab double-knockout mice. Our results indicate that the combined consideration of both the medication's capacity to act as an ABCB1-transporter substrate and the patient's ABCB1 genotype are strong predictors for achieving a remission. This finding can be viewed as a further step into personalized antidepressant treatment.
Uhr
Manfred
M
Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804 Munich, Germany. uhr@mpipsykl.mpg.de
Tontsch
Alina
A
Namendorf
Christian
C
Ripke
Stephan
S
Lucae
Susanne
S
Ising
Marcus
M
Dose
Tatjana
T
Ebinger
Martin
M
Rosenhagen
Marcus
M
Kohli
Martin
M
Kloiber
Stefan
S
Salyakina
Daria
D
Bettecken
Thomas
T
Specht
Michael
M
Pütz
Benno
B
Binder
Elisabeth B
EB
Müller-Myhsok
Bertram
B
Holsboer
Florian
F
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D018709:Statistics, Nonparametric
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000928:Antidepressive Agents; C507084:Abcb1b protein, mouse