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Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women

Brain-derived neurotrophic factor (BDNF) has previously been associated with the pathogenesis of both emotionally unstable personality disorder (EUPD) and suicidal behavior. No study has yet investigated BDNF-associated epigenetic alterations in a group of severely impaired EUPD and suicidal patient...

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Autores principales: Jamshidi, Esmail, Boström, Adrian E. Desai, Wilczek, Alexander, Nilsonne, Åsa, Åsberg, Marie, Jokinen, Jussi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913473/
https://www.ncbi.nlm.nih.gov/pubmed/36766691
http://dx.doi.org/10.3390/cells12030350
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author Jamshidi, Esmail
Boström, Adrian E. Desai
Wilczek, Alexander
Nilsonne, Åsa
Åsberg, Marie
Jokinen, Jussi
author_facet Jamshidi, Esmail
Boström, Adrian E. Desai
Wilczek, Alexander
Nilsonne, Åsa
Åsberg, Marie
Jokinen, Jussi
author_sort Jamshidi, Esmail
collection PubMed
description Brain-derived neurotrophic factor (BDNF) has previously been associated with the pathogenesis of both emotionally unstable personality disorder (EUPD) and suicidal behavior. No study has yet investigated BDNF-associated epigenetic alterations in a group of severely impaired EUPD and suicidal patients. The discovery cohort consisted of 97 women with emotionally unstable personality disorder (EUPD) with at least two serious suicide attempts (SAs) and 32 healthy female controls. The genome-wide methylation pattern was measured by the Illumina EPIC BeadChip and analyzed by robust linear regression models to investigate mean BDNF methylation levels in a targeted analysis conditioned upon severity of suicide attempt. The validation cohort encompassed 60 female suicide attempters, stratified into low- (n = 45) and high-risk groups (n = 15) based on degree of intent-to-die and lethality of SA method, and occurrence of death-by-suicide at follow-up. Mean BDNF methylation levels exhibited increased methylation in relation to EUPD (p = 0.0159, percentage mean group difference ~3.8%). Similarly, this locus was confirmed as higher-methylated in an independent cohort of females with severe suicidal behavior (p = 0.0300). Results were independent of age and BMI. This is the first study to reveal emerging evidence of epigenetic dysregulation of BDNF with dependence on features known to confer increased risk of suicide deaths (lethality of suicide-attempt method and presence of EUPD diagnosis with history of recent SAs). Further studies investigating epigenetic and genetic effects of BDNF on severe suicidal behavior and EUPD are needed to further elucidate the role of epigenetic regulatory mechanisms and neurotrophic factors in relation to suicide and EUPD, and hold potential to result in novel treatment methods.
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spelling pubmed-99134732023-02-11 Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women Jamshidi, Esmail Boström, Adrian E. Desai Wilczek, Alexander Nilsonne, Åsa Åsberg, Marie Jokinen, Jussi Cells Article Brain-derived neurotrophic factor (BDNF) has previously been associated with the pathogenesis of both emotionally unstable personality disorder (EUPD) and suicidal behavior. No study has yet investigated BDNF-associated epigenetic alterations in a group of severely impaired EUPD and suicidal patients. The discovery cohort consisted of 97 women with emotionally unstable personality disorder (EUPD) with at least two serious suicide attempts (SAs) and 32 healthy female controls. The genome-wide methylation pattern was measured by the Illumina EPIC BeadChip and analyzed by robust linear regression models to investigate mean BDNF methylation levels in a targeted analysis conditioned upon severity of suicide attempt. The validation cohort encompassed 60 female suicide attempters, stratified into low- (n = 45) and high-risk groups (n = 15) based on degree of intent-to-die and lethality of SA method, and occurrence of death-by-suicide at follow-up. Mean BDNF methylation levels exhibited increased methylation in relation to EUPD (p = 0.0159, percentage mean group difference ~3.8%). Similarly, this locus was confirmed as higher-methylated in an independent cohort of females with severe suicidal behavior (p = 0.0300). Results were independent of age and BMI. This is the first study to reveal emerging evidence of epigenetic dysregulation of BDNF with dependence on features known to confer increased risk of suicide deaths (lethality of suicide-attempt method and presence of EUPD diagnosis with history of recent SAs). Further studies investigating epigenetic and genetic effects of BDNF on severe suicidal behavior and EUPD are needed to further elucidate the role of epigenetic regulatory mechanisms and neurotrophic factors in relation to suicide and EUPD, and hold potential to result in novel treatment methods. MDPI 2023-01-17 /pmc/articles/PMC9913473/ /pubmed/36766691 http://dx.doi.org/10.3390/cells12030350 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jamshidi, Esmail
Boström, Adrian E. Desai
Wilczek, Alexander
Nilsonne, Åsa
Åsberg, Marie
Jokinen, Jussi
Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women
title Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women
title_full Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women
title_fullStr Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women
title_full_unstemmed Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women
title_short Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women
title_sort increased methylation of brain-derived neurotrophic factor (bdnf) is related to emotionally unstable personality disorder and severity of suicide attempt in women
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913473/
https://www.ncbi.nlm.nih.gov/pubmed/36766691
http://dx.doi.org/10.3390/cells12030350
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