Hen Hallevi, Oren Tene, Jeremy Molad, Aviva Alpernas, Dana Niry, Saly Usher, Lital Feldinger, Estelle Seyman, Einor Ben Assayag
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引用次数: 0
Abstract
Background: Up to 25% of stroke survivors develop post-traumatic stress disorder (PTSD) symptoms, yet the predisposing factors remain largely unknown. The C-C-Chemokine receptor-5 gene (CCR5) loss-of-function mutation (LOFM, CCR5-Δ32) has been identified as a protective factor against post-stroke depression. This study investigates whether CCR5-Δ32 also confers protection against post-stroke PTSD, in conjunction with two additional polymorphisms: the 5-HTTLPR in the serotonin transporter gene and the BDNF Val66Met variant.
Methods: We conducted a prospective analysis of 432 survivors of first-ever mild-to-moderate ischemic stroke, assessing PTSD symptomatology at 6, 12, and 24 months post-stroke. Genetic screening for CCR5-Δ32 status and PTSD symptom data were available for these participants.
Results: PTSD was diagnosed in 48 participants (11%) within the first year post-stroke. CCR5-Δ32 carriers exhibited significantly fewer PTSD symptoms at 6, 12, and 24 months compared to non-carriers (P < .001, P < .001, P = .02, respectively), with sustained improvement over time. Multivariate analysis confirmed that CCR5-Δ32 status was independently associated with lower PTSD risk after adjusting for relevant confounders. Furthermore, individuals with a maladaptive coping style who were non-carriers of CCR5-Δ32 exhibited a higher risk of PTSD development (HR = 4.03; 95% CI, 1.95-6.32, P < .001). Carriers of both 5-HTTLPR-L and CCR5-Δ32 had significantly lower PTSD symptoms at 6 and 12 months post-stroke (P = .026, P = .05), as did carriers of both the BDNF Val allele and CCR5-Δ32 at 6 months (P = .022).
Conclusions: Our findings suggest that CCR5-Δ32 carriers are less likely to develop PTSD symptoms following stroke, including individuals with pre-existing maladaptive coping styles. These results highlight a potential genetic target for future intervention strategies, with CCR5 blockade emerging as a promising therapeutic avenue for post-stroke PTSD prevention.
背景：高达25%的中风幸存者会出现创伤后应激障碍（PTSD）症状，但其诱发因素在很大程度上仍然未知。c - c趋化因子受体-5基因（CCR5）功能丧失突变（LOFM, CCR5-Δ32）已被确定为卒中后抑郁的保护因素。这项研究调查了CCR5-Δ32是否也与另外两种多态性（血清素转运基因中的5-HTTLPR和BDNF Val66Met变异）一起，对中风后PTSD有保护作用。方法：我们对432例首次轻度至中度缺血性卒中幸存者进行了前瞻性分析，在卒中后6、12和24个月评估PTSD症状。对这些参与者进行CCR5-Δ32状态和PTSD症状的遗传筛查。结果：48名参与者（11%）在中风后一年内被诊断出PTSD。与非携带者相比，CCR5-Δ32携带者在6、12和24个月时表现出的PTSD症状显著减少(P P P =。（分别为02），并随着时间的推移持续改善。多因素分析证实，在调整相关混杂因素后，CCR5-Δ32状态与较低的PTSD风险独立相关。此外，非CCR5-Δ32携带者的适应不良应对方式个体表现出更高的PTSD发展风险(HR = 4.03；95% ci, 1.95 ~ 6.32, p p =。026, P = 0.05)， BDNF Val等位基因和CCR5-Δ32携带者在6个月时也是如此（P = 0.022）。结论：我们的研究结果表明，CCR5-Δ32携带者不太可能在中风后出现PTSD症状，包括先前存在适应不良应对方式的个体。这些结果强调了未来干预策略的潜在基因靶点，CCR5阻断正在成为卒中后PTSD预防的有希望的治疗途径。
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