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Elevated plasma brain-derived neurotrophic factor as a potential risk biomarker for major depressive disorder in middle-aged women : A nested case-control study

Wang, Xiao LU ; Memon, Ashfaque A LU orcid ; Hedelius, Anna LU ; Grundberg, Anton LU ; Sundquist, Jan LU and Sundquist, Kristina LU (2025) In Journal of Affective Disorders 392.
Abstract

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a critical role in neuronal development and neural connectivity, and has been implicated in the pathophysiology of Major Depressive Disorder (MDD). However, its predictive value for MDD onset remains unclear. This study examined whether baseline BDNF levels are associated with incident MDD in middle-aged women.

MATERIAL AND METHODS: In this nested case-control study, 104 individuals (mean age = 56.0) without MDD at baseline were selected from a population-based follow-up cohort. Over five years, 52 developed MDD (cases) and 52 remained MDD-free (controls). Baseline plasma BDNF levels were measured using a Luminex assay. Associations between BDNF levels and MDD risk were... (More)

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a critical role in neuronal development and neural connectivity, and has been implicated in the pathophysiology of Major Depressive Disorder (MDD). However, its predictive value for MDD onset remains unclear. This study examined whether baseline BDNF levels are associated with incident MDD in middle-aged women.

MATERIAL AND METHODS: In this nested case-control study, 104 individuals (mean age = 56.0) without MDD at baseline were selected from a population-based follow-up cohort. Over five years, 52 developed MDD (cases) and 52 remained MDD-free (controls). Baseline plasma BDNF levels were measured using a Luminex assay. Associations between BDNF levels and MDD risk were assessed using multivariable logistic regression adjusted for age and BMI.

RESULTS: MDD cases exhibited significantly higher baseline plasma BDNF levels compared to controls (median: 2683 vs 1844 pg/ml, p = 0.01). Elevated BDNF was associated with increased MDD risk in the univariate analysis (OR = 1.78, 95 % CI = 1.20-2.78, p = 0.006) and remained significant after adjusting for age, BMI, lifestyle, and socioeconomic factors (fully adjusted OR = 1.84, 95 % CI = 1.20-3.02, p = 0.009). BDNF elevation was most pronounced in MDD cases diagnosed 2-5 years after baseline.

CONCLUSION: Our findings challenge the view that BDNF is solely protective against MDD, as our study links higher plasma BDNF levels to increased MDD risk. These results suggest that higher BDNF levels may reflect underlying mechanisms contributing to MDD onset, highlighting the need to further investigate BDNF's role as a potential risk biomarker.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Affective Disorders
volume
392
article number
120202
publisher
Elsevier
external identifiers
  • pmid:40912327
  • scopus:105015076037
ISSN
0165-0327
DOI
10.1016/j.jad.2025.120202
language
English
LU publication?
yes
additional info
Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
id
549189d6-bfd4-44bb-a535-2343a6aed18d
date added to LUP
2025-09-09 09:08:30
date last changed
2025-10-14 10:38:37
@article{549189d6-bfd4-44bb-a535-2343a6aed18d,
  abstract     = {{<p>BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a critical role in neuronal development and neural connectivity, and has been implicated in the pathophysiology of Major Depressive Disorder (MDD). However, its predictive value for MDD onset remains unclear. This study examined whether baseline BDNF levels are associated with incident MDD in middle-aged women.</p><p>MATERIAL AND METHODS: In this nested case-control study, 104 individuals (mean age = 56.0) without MDD at baseline were selected from a population-based follow-up cohort. Over five years, 52 developed MDD (cases) and 52 remained MDD-free (controls). Baseline plasma BDNF levels were measured using a Luminex assay. Associations between BDNF levels and MDD risk were assessed using multivariable logistic regression adjusted for age and BMI.</p><p>RESULTS: MDD cases exhibited significantly higher baseline plasma BDNF levels compared to controls (median: 2683 vs 1844 pg/ml, p = 0.01). Elevated BDNF was associated with increased MDD risk in the univariate analysis (OR = 1.78, 95 % CI = 1.20-2.78, p = 0.006) and remained significant after adjusting for age, BMI, lifestyle, and socioeconomic factors (fully adjusted OR = 1.84, 95 % CI = 1.20-3.02, p = 0.009). BDNF elevation was most pronounced in MDD cases diagnosed 2-5 years after baseline.</p><p>CONCLUSION: Our findings challenge the view that BDNF is solely protective against MDD, as our study links higher plasma BDNF levels to increased MDD risk. These results suggest that higher BDNF levels may reflect underlying mechanisms contributing to MDD onset, highlighting the need to further investigate BDNF's role as a potential risk biomarker.</p>}},
  author       = {{Wang, Xiao and Memon, Ashfaque A and Hedelius, Anna and Grundberg, Anton and Sundquist, Jan and Sundquist, Kristina}},
  issn         = {{0165-0327}},
  language     = {{eng}},
  month        = {{09}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Affective Disorders}},
  title        = {{Elevated plasma brain-derived neurotrophic factor as a potential risk biomarker for major depressive disorder in middle-aged women : A nested case-control study}},
  url          = {{http://dx.doi.org/10.1016/j.jad.2025.120202}},
  doi          = {{10.1016/j.jad.2025.120202}},
  volume       = {{392}},
  year         = {{2025}},
}