A preliminary investigation of the influence of CREB1 gene on treatment resistance in major depression

J Affect Disord. 2011 Jan;128(1-2):56-63. doi: 10.1016/j.jad.2010.06.025.


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.

Limitations: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antidepressive Agents / therapeutic use*
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / psychology
  • Drug Resistance / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Remission Induction
  • Risk Factors
  • Sampling Studies
  • Treatment Outcome


  • Antidepressive Agents
  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein