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. 2024 May 31;22(2):306-313.
doi: 10.9758/cpn.23.1115. Epub 2023 Sep 1.

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

Hee-Ju Kang  1 , Ju-Wan Kim  1 , Joon-Tae Kim  2 , Man-Seok Park  2 , Byung Jo Chun  3 , Sung-Wan Kim  1 , Il-Seon Shin  1 , Robert Stewart  4   5 , Jae-Min Kim  1
Affiliations

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

Hee-Ju Kang et al. Clin Psychopharmacol Neurosci. .

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.

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

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Conflict of interest statement

Conflicts of Interest

Jae-Min Kim declares research support in the last 5 years from Janssen and Lundbeck. Sung-Wan Kim declares research support in the last 5 years from Janssen, Boehringer Ingelheim, Allergan and Otsuka. All other authors report no biomedical financial interests or potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Study outline and participant recruitment process.
Fig. 2
Fig. 2
Association of the average BDNF methylation value with the cumulative incidence (%) of composite cerebro-cardiovascular events, stratified by SI status immediately after stroke (within 2 weeks). Cox proportional hazards models were used for analyses of the overall cohort, and for analyses stratified by SI after adjustment for age, NIHSS score, stroke hemisphere, previous history of stroke, presence of cardiac disease, and depression (according to the DSM-IV criteria) within 2 weeks after stroke. The interaction effect between average BDNF methylation value and SI on composite CCVEs was not significant (p = 0.121). SI, suicidal ideation; NIHSS, National Institutes of Health Stroke Scale; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th edition; BDNF, brain derived neurotrophic factor; CCVEs, cerebro-cardiovascular events. *Represents statistical significance (p value < 0.05).
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