A preliminary investigation of the influence of CREB1 gene on treatment resistance in major depression.
BACKGROUND
The transcription factor Cyclic adenosine monophosphate Response Element Binding (CREB) protein has been repeatedly involved in the aetiology and pharmacotherapy of major depression (MD). The aim of this study was to investigate the potential association of a set of single nucleotide polymorphisms (SNPs) in CREB1 gene and both MD and response, remission and treatment resistance to antidepressants.


METHODS
One hundred-ninety MD patients collected in the context of a resistant depression study and treated with antidepressants for at least 4weeks were genotyped for 5 CREB1 SNPs (rs2709376, rs2253206, rs7569963, rs7594560, and rs4675690). Response, remission and treatment resistance were recorded.


RESULTS
An allele of rs7569963 as well as rs2253206-rs7569963 A-A and rs7569963-rs4675690 A-C haplotypes were associated with the status of treatment resistance. Additionally, rs7569963 GG genotype was positively associated with remission. No further significant associations were observed.


CONCLUSIONS
Limitations of the present study include a relatively small sample size and the incomplete ascertainment of data which could influence the outcome.


CONCLUSIONS
Our results preliminary suggest that some genetic polymorphisms in CREB1 could be associated to treatment resistance. Although such finding needs to be replicated in larger samples, it increases current knowledge about the genetic predictors of response to antidepressants that will probably lead to enhance treatment outcomes by addressing each individual to the most appropriate treatment strategy in the early stages of treatment.
Serretti
Alessandro
A
Institute of Psychiatry, University of Bologna, Bologna, Italy. alessandro.serretti@unibo.it
Chiesa
Alberto
A
Calati
Raffaella
R
Massat
Isabelle
I
Linotte
Sylvie
S
Kasper
Siegfried
S
Lecrubier
Yves
Y
Antonijevic
Irina
I
Forray
Carlos
C
Snyder
Lenore
L
Bollen
Joseph
J
Zohar
Joseph
J
De Ronchi
Diana
D
Souery
Daniel
D
Mendlewicz
Julien
J
D000328:Adult; D000368:Aged; D000483:Alleles; D000928:Antidepressive Agents / Q000627:therapeutic use*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012074:Remission Induction; D012307:Risk Factors; D012494:Sampling Studies; D016896:Treatment Outcome
D000928:Antidepressive Agents; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein