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

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

J Psychiatry Neurosci 2021;46(4):E431-E440 | PDF | Appendix

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

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.

Submitted Oct. 20, 2020; Revised Jan. 11, 2021; Accepted Jan. 22, 2021

Acknowledgements: This study is supported by grants RAG11482 from the American Federation for Aging Research, 2011344 from the U.S.–Israel Bi-national Science Foundation, AARG-16-442861 from the Alzheimer’s Association, PTCG-20-706182 from Part the Cloud-Gates Partnership Grant Program and the Alzheimer’s Association, and a grant from Rekanati Foundation.

Affiliations: From the Departments of Neurology and Psychiatry, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (Tene, Hallevi, Molad, Usher, Seyman, Shenhar-Tsarfaty, Ben Assayag); the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Tene, Hallevi, Bornstein, Shenhar-Tsarfaty, Ben Assayag); and the Brain Center, Shaare Zedek Medical Center, Jerusalem, Israel (Bornstein).

Competing interests: None declared.

Contributors: O. Tene, N. Bornstein, S. Shenhar-Tsarfaty and E. Ben Assayag designed the study. O. Tene, H. Hallevi, J. Molad, S. Usher, N. Bornstein and E. Ben Assayag acquired the data, which O. Tene, J. Molad, E. Seyman and E. Ben Assayag analyzed. O. Tene and E. Bassayag wrote the article, which H. Hallevi, J. Molad, S. Usher, E. Seyman, N. Bornstein and S. Shenhar-Tsarfaty reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

Clinical trial registration:
Identifier: NCT01926691

Content licence: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BYNC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is non-commercial (i.e. research or educational use), and no modifications or adaptations are made. See:

DOI: 10.1503/jpn.200197

Correspondence to: E. Ben Assayag, Department of Neurology, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel;