Brain Derived Neurotrophic Factor Methylation and Long-term Outcomes after Stroke Interacting with Suicidal Ideation
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (42)
- GBD 2019 Stroke Collaborators, "Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019", Lancet Neurol, 20, pp.795~820 (2021)
- Cramer SC, "Repairing the human brain after stroke : I. Mechanisms of spontaneous recovery", Ann Neurol, 63, pp.272~287 (2008)
- Wijnhoud AD, "Prediction of major vascular events in patients with transient ischemic attack or ischemic stroke : a comparison of 7 models", Stroke, 41, pp.2178~2185 (2010)
- Arntz RM, "The very long-term risk and predictors of recurrent ischaemic events after a stroke at a young age : The FUTURE study", Eur Stroke J, 1, pp.337~345 (2016)
- Boulanger M, "Long-term risk of myocardial infarction compared to recurrent stroke after transient ischemic attack and ischemic stroke : systematic review and meta-analysis", J Am Heart Assoc, 7, pp.e007267~ (2018)
- Vogt G, "Initial lesion volume is an independent predictor of clinical stroke outcome at day 90 : an analysis of the Virtual International Stroke Trials Archive(VISTA)database", Stroke, 43, pp.1266~1272 (2012)
- Cheng B, "Influence of stroke infarct location on functional outcome measured by the modified rankin scale", Stroke, 45, pp.1695~1702 (2014)
- Stinear CM, "The PREP algorithm predicts potential for upper limb recovery after stroke", Brain, 135, pp.2527~2535 (2012)
- Math N, "Influences of genetic variants on stroke recovery : a metaanalysis of the 31, 895 cases", Neurol Sci, 40, pp.2437~2445 (2019)
- Lu B, "BDNF and activity-dependent synaptic modulation", Learn Mem, 10, pp.86~98 (2003)
- Schäbitz WR, "Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia", Stroke, 31, pp.2212~2217 (2000)
- Almeida RD, "Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways", Cell Death Differ, 12, pp.1329~1343 (2005)
- Mang CS, "Promoting neuroplasticity for motor rehabilitation after stroke : considering the effects of aerobic exercise and genetic variation on brain-derived neurotrophic factor", Phys Ther, 93, pp.1707~1716 (2013)
- Clarkson AN, "Cortical excitability and post-stroke recovery", Biochem Soc Trans, 37, pp.1412~1414 (2009)
- Egan MF, "The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function", Cell, 112, pp.257~269 (2003)
- Hochberg Z, "Child health, developmental plasticity, and epigenetic programming", Endocr Rev, 32, pp.159~224 (2011)
- Martinowich K, "DNA methylation-related chromatin remodeling in activitydependent BDNF gene regulation", Science, 302, pp.890~893 (2003)
- Santoro M, "BDNF rs6265 polymorphism and its methylation in patients with stroke undergoing rehabilitation", Int J Mol Sci, 21, pp.8438~ (2020)
- Vyas MV, "Association Between stroke and subsequent risk of suicide : a systematic review and meta-analysis", Stroke, 52, pp.1460~1464 (2021)
- Pandey GN, "Biological basis of suicide and suicidal behavior", Bipolar Disord, 15, pp.524~541 (2013)
- Kang HJ, "Association of SLC6A4 methylation with long-term outcomes after stroke : focus on the interaction with suicidal ideation", Sci Rep, 11, pp.2710~ (2021)
- Kim JM, "Impact of suicidal ideation on long-term cardiac outcomes in patients with acute coronary syndrome : sex-specific differences", Psychother Psychosom, 87, pp.311~312 (2018)
- Eisen RB, "Association between BDNF levels and suicidal behaviour : a systematic review and meta-analysis", Syst Rev, 4, pp.187~ (2015)
- Roy B, "DNA methylation and expression of stress related genes in PBMC of MDD patients with and without serious suicidal ideation", J Psychiatr Res, 89, pp.115~124 (2017)
- Kim JM, "A longitudinal study of SLC6A4 DNA promoter methylation and poststroke depression", J Psychiatr Res, 47, pp.1222~1227 (2013)
- Montgomery SA, "A new depression scale designed to be sensitive to change", Br J Psychiatry, 134, pp.382~389 (1979)
- Santos CO, "A study of suicidal thoughts in acute stroke patients", J Stroke Cerebrovasc Dis, 21, pp.749~754 (2012)
- Kim JM, "Serotonergic genes and suicidal ideation 2 weeks and 1 year after stroke in Korea", Am J Geriatr Psychiatry, 22, pp.980~988 (2014)
- Lim JS, "Prediction models for suicide attempts among adolescents using machine learning techniques", Clin Psychopharmacol Neurosci, 20, pp.609~620 (2022)
- Kang HJ, "Longitudinal associations between BDNF promoter methylation and late-life depression", Neurobiol Aging, 36, pp.1764~ (2015)
- Roth TL, "Lasting epigenetic influence of early-life adversity on the BDNF gene", Biol Psychiatry, 65, pp.760~769 (2009)
- Kang HJ, "BDNF methylation and suicidal ideation in patients with acute coronary syndrome", Psychiatry Investig, 15, pp.1094~1097 (2018)
- Kim JM, "Associations of BDNF genotype and promoter methylation with acute and long-term stroke outcomes in an East Asian cohort", PLoS One, 7, pp.e51280~ (2012)
- Breitling LP, "Smoking, F2RL3 methylation, and prognosis in stable coronary heart disease", Eur Heart J, 33, pp.2841~2848 (2012)
- Popova NK, "Neuronal and behavioral plasticity : the role of serotonin and BDNF systems tandem", Expert Opin Ther Targets, 23, pp.227~239 (2019)
- Calabrese F, "Brain-derived neurotrophic factor : a bridge between inflammation and neuroplasticity", Front Cell Neurosci, 8, pp.430~ (2014)
- ADAM and heart rate variability measurement, "Clin Psychopharmacol Neurosci", 2022, 271~278
- Karege F, "Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs", Brain Res Mol Brain Res, 136, pp.29~37 (2005)
- Posner K, "The columbia-suicide severity rating scale : initial validity and internal consistency findings from three multisite studies with adolescents and adults", Am J Psychiatry, 168, pp.1266~1277 (2011)
- Green KL, "The predictive validity of the beck depression inventory suicide item", J Clin Psychiatry, 76, pp.1683~1686 (2015)
- Murrough JW, "Ketamine for rapid reduction of suicidal ideation : a randomized controlled trial", Psychol Med, 45, pp.3571~3580 (2015)
- Rami FZ, "Risperidone induced DNA methylation changes in dopamine receptor and stathmin genes in mice exposed to social defeat stress", Clin Psychopharmacol Neurosci, 20, pp.373~388 (2022)