Clin Psychopharmacol Neurosci.  2024 May;22(2):306-313. 10.9758/cpn.23.1115.

Brain Derived Neurotrophic Factor Methylation and Long-term Outcomes after Stroke Interacting with Suicidal Ideation

• Kang HJ
• Kim JW
• Kim JT
• Park MS
• Chun BJ
• Kim SW
• Shin IS
• Stewart R
• Kim JM

• KMID: 2556423
• DOI: http://doi.org/10.9758/cpn.23.1115

Abstract

Objective
This study aimed to evaluate the unexplored relationship between BDNF methylation, long-term outcomes, and its interaction with suicidal ideation (SI), which is closely associated with both BDNF expression and stroke outcomes.
Methods
A total of 278 stroke patients were assessed for BDNF methylation status and SI using suicide-related item in the Montgomery–Åsberg Depression Rating Scale at 2 weeks post-stroke. We investigated the incidence of composite cerebro-cardiovascular events (CCVEs) during an 8−14-year period after the initial stroke as long-term stroke outcome. We conducted Cox regression models adjusted for covariates to evaluate the association between BDNF methylation status and CCVEs, as well as its interaction with post-stroke SI at 2 weeks.
Results
Higher methylation status of CpG 1, 3, and 5, but not the average value, predicted a greater number of composite CCVEs during 8−14 years following the stroke. The associations between a higher methylation status of CpGs 1, 3, 5, and 8, as well as the average BDNF methylation value, and a greater number of composite CCVEs, were prominent in patients who had post-stroke SI at 2 weeks. Notably, a significant interaction between methylation status and SI on composite CCVEs was observed only for CpG 8.
Conclusion
The significant association between BDNF methylation and poor long-term stroke outcomes, particularly amplified in individuals who had post-stroke SI at 2 weeks, suggested that evaluating the biological marker status of BDNF methylation along with assessing SI during the acute phase of stroke can help predict long-term outcomes.

Keyword

Stroke; Suicidal ideation; Methylation; Brain-derived neurotrophic factor; Outcome assessment