Halaris Angelos, Hain Daniel, Law Rebecca, Brown Lisa, Lewis David, Filip Maria
Loyola University School of Medicine and Loyola University Medical Center, 2160 South First Ave., Maywood, IL, 60153, USA.
Myriad Neuroscience, 6960 Cintas Blvd, Mason, OH, 45040, USA.
Brain Behav Immun Health. 2023 Apr 20;30:100625. doi: 10.1016/j.bbih.2023.100625. eCollection 2023 Jul.
Affective illness has been associated with a proinflammatory state, and it is generally accepted that the immune system plays a key role in the pathophysiology of mood disorders. Since inflammatory biomarkers are elevated in bipolar disorder, anti-inflammatory combination therapies may enhance response and reverse treatment resistance.
In the present study we investigated the possible impact of single nucleotide polymorphisms (SNPs) within the CRP gene on CRP blood levels, treatment response and level-of-stress perception in our cohort of treatment-resistant bipolar-depressed patients receiving escitalopram and celecoxib, or escitalopram and placebo, as previously reported (Halaris et al., 2020).
Study design, clinical findings, and CRP blood levels have been reported previously (Halaris et al., 2020; Edberg et al., 2018). In this follow-up study we extracted DNA from blood cells collected at baseline. Genome-wide genotyping was performed for all subjects using the Infinium Multi-Ethnic Global-8 v1.0 Kit. Based on reports in the literature indicating possible associations with psychiatric conditions, ten previously reported gene polymorphisms were evaluated in a preliminary analysis. We focused on rs3093059 and rs3093077 were in complete LD. Carriers were defined as those possessing at least one C allele for rs3093059, or at least one G allele for rs3093077. Additionally, we determined blood levels of the medications administered.
Non-carriers of rs3093059 and rs3093077 had significantly lower baseline CRP blood levels than carriers (p = 0.03). Increased rates of HAM-D17 response (p = 0.21) and remission (p = 0.13) and lower PSS-14 scores (p = 0.13) were observed in non-carriers among subjects receiving celecoxib but they did not reach statistical significance. When examining all subjects, nominally significant associations between carrier-status and remission (p = 0.04) and PSS-14 scores (p = 0.04) were observed after correcting for treatment arm. Non-carriers receiving celecoxib had the highest rates of response and remission, and the lowest stress scores.
Carriers of the CRP SNPs may have higher baseline CRP levels, although non-carriers appear to benefit more from celecoxib co-therapy. Determination of the carrier status in conjunction with pretreatment blood CRP level measurement may contribute to personalized psychiatric practice, but replication of the present findings is needed.
情感性疾病与促炎状态有关，免疫系统在情绪障碍的病理生理学中起关键作用这一观点已被广泛接受。由于双相情感障碍患者的炎症生物标志物升高，抗炎联合疗法可能会增强疗效并逆转治疗抵抗。
在本研究中，我们调查了CRP基因内单核苷酸多态性（SNP）对我们之前报道的（Halaris等人，2020年）接受艾司西酞普兰和塞来昔布或艾司西酞普兰和安慰剂治疗的难治性双相抑郁患者队列中CRP血液水平、治疗反应和应激感知水平的可能影响。
研究设计、临床发现和CRP血液水平此前已有报道（Halaris等人，2020年；Edberg等人，2018年）。在这项随访研究中，我们从基线时采集的血细胞中提取DNA。使用Infinium多民族全球8 v1.0试剂盒对所有受试者进行全基因组基因分型。根据文献报道的与精神疾病可能的关联，在初步分析中评估了十个先前报道的基因多态性。我们重点关注处于完全连锁不平衡状态的rs3093059和rs3093077。携带者定义为rs3093059至少拥有一个C等位基因或rs3093077至少拥有一个G等位基因的个体。此外，我们测定了所给药的血液水平。
rs3093059和rs3093077的非携带者基线CRP血液水平显著低于携带者（p = 0.03）。在接受塞来昔布治疗的受试者中，非携带者的汉密尔顿抑郁量表17项（HAM-D17）反应率（p = 0.21）和缓解率（p = 0.13）有所提高，压力感知量表14项（PSS-14）评分较低（p = 0.13），但未达到统计学意义。在检查所有受试者时，校正治疗组后，观察到携带者状态与缓解（p = 0.04）和PSS-14评分（p = 0.04）之间存在名义上的显著关联。接受塞来昔布治疗的非携带者反应率和缓解率最高，压力评分最低。
CRP单核苷酸多态性的携带者可能具有较高的基线CRP水平，尽管非携带者似乎从塞来昔布联合治疗中获益更多。结合治疗前血液CRP水平测量来确定携带者状态可能有助于个性化精神科实践，但需要重复本研究结果。
