Institute of Psychiatry, University of Bologna, Bologna, Italy.
J Affect Disord. 2011 Jan;128(1-2):56-63. doi: 10.1016/j.jad.2010.06.025.
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.
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.
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 of the present study include a relatively small sample size and the incomplete ascertainment of data which could influence the outcome.
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.
转录因子环磷酸腺苷反应元件结合（CREB）蛋白已反复涉及到主要抑郁症（MD）的病因和药物治疗。本研究的目的是探讨 CREB1 基因一组单核苷酸多态性（SNPs）与 MD 以及抗抑郁药的反应、缓解和治疗抵抗之间的潜在关联。
在一项难治性抑郁症研究中收集的 190 名 MD 患者，接受抗抑郁药治疗至少 4 周，对 5 个 CREB1 SNPs（rs2709376、rs2253206、rs7569963、rs7594560 和 rs4675690）进行基因分型。记录反应、缓解和治疗抵抗。
rs7569963 的一个等位基因以及 rs2253206-rs7569963 A-A 和 rs7569963-rs4675690 A-C 单倍型与治疗抵抗状态相关。此外，rs7569963 GG 基因型与缓解呈正相关。未观察到其他显著相关性。
本研究的局限性包括样本量相对较小以及数据不完全确定，这可能会影响结果。
我们的初步结果表明，CREB1 中的一些遗传多态性可能与治疗抵抗有关。尽管需要在更大的样本中复制这些发现，但它增加了当前对抗抑郁药反应的遗传预测因子的知识，这可能通过在治疗早期针对每个个体采用最合适的治疗策略来提高治疗效果。
