Post-Stroke PTSD: The Protective Role of CCR5-Δ32 Polymorphism

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.

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.

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).

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.