CCR5-Δ32 polymorphism: A possible protective factor for post-stroke depressive symptoms

Oren Tene, Hen Hallevi, Jeremy Molad, Saly Usher, Estelle Seyman, Natan M. Bornstein, Shani Shenhar-Tsarfaty, Einor Ben Assayag*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: A naturally occurring loss-of-function mutation in the gene for C-C chemokine receptor type 5 (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether this mutation also prevented the development of depressive symptoms up to 2 years after a stroke. Methods: Participants were survivors of a first-ever mild to moderate ischemic stroke or transient ischemic attack from the TABASCO prospective study who underwent a 3 T MRI at baseline and were examined by a multiprofessional team 6, 12 and 24 months after the event, including an evaluation of depressive symptoms using the Geriatric Depression Scale. Results: CCR5-Δ32 status and a baseline depression evaluation were available for 435 patients. Compared with noncarriers, CCR5-Δ32 carriers (16.1%) had fewer depressive symptoms at admission (p = 0.035) and at 6 months (p < 0.001), 12 months (p < 0.001) and 24 months (p = 0.006) after the index event. This association remained significant at 6 and 12 months after adjustment for age, sex, education, antidepressant use, ethnicity and the presence of cortical infarcts. These findings were more robust in women. Compared to baseline, depressive symptoms in CCR5-Δ32 noncarriers tended to remain stable or grow worse over time, but in CCR5-Δ32 carriers, symptoms tended to improve. Limitations: A limitation of this study was the exclusion of patients who had a severe stroke or who had pre-stroke depression. Conclusion: Carriers of the CCR5-Δ32 allele had a lower tendency to develop depressive symptoms post-stroke, and this phenomenon was more prominent in women. These findings could have clinical implications; they suggest a mechanism-based treatment target for post-stroke depression. Drugs mimicking this loss-of-function mutation exist and could serve as a novel antidepressant therapy.

Original languageEnglish
Pages (from-to)E431-E440
JournalJournal of Psychiatry and Neuroscience
Volume46
Issue number4
DOIs
StatePublished - 1 Jul 2021

Funding

FundersFunder number
Rekanati Foundation
U.S.–Israel Bi-national Science FoundationAARG-16-442861
Alzheimer's AssociationPTCG-20-706182
American Federation for Aging Research2011344
United States-Israel Binational Science Foundation

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