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

Abstract 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 4 weeks 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.