Epigenetic modulation of BDNF gene: Differences in DNA methylation between unipolar and bipolar patients
Abstract
Background The brain derived neurotrophic factor (BDNF) gene and its epigenetic regulation have been repeatedly implicated in the pathophysiology of mood disorders. Following previous investigation in the field, we further investigated differences in BDNF promoter gene methylation in patients with mood disorders, comparing unipolar and bipolar subjects, on the basis of illness phase, gender, age and psychotropic prescription.Methods 154 patients (43 MDD; 61 BD I; 50 BD II), on stable pharmacological treatment, and 44 age-matched, healthy controls were recruited. BDNF methylation levels from peripheral blood mononuclear cells (PBMCs) were compared by analysis of variance followed by Bonferroni׳s post-hoc test.Results Similar, higher levels of BDNF gene promoter methylation were found in BD II and MDD patients, compared to BD I subjects (P<0.01). When stratified on the basis of mood status, methylation levels of depressed patients were significantly higher, compared to the levels of manic/mixed patients (P<0.01). While gender and age did not seem to influence methylation levels of BDNF gene promoter, patients on lithium and valproate showed overall lower levels.Limitations Cross-sectional analysis using PBMCs with further investigation with larger samples, including drug-naïve patients, needed to replicate findings in neuronal cells.Conclusions Present data confirm our previous results of higher methylation levels in BD II (compared to BD I) and MDD patients (compared to controls). A closer relationship between BD II and MDD, compared to BD I patients as well an association of lower methylation levels with the presence of mania/mixed state, compared to the depressive phase, was observed.
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In BD, epigenetic signatures are often state-dependent, with methylation differing in manic and depressive states compared to euthymic states.
“In BD, epigenetic signatures are often state-dependent, with methylation differing in manic and depressive states compared to euthymic states”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [16]
There is extensive evidence of a difference in DNAm in BDNF, as well as EWAS studies showing enrichment for the neurogenesis pathway in SCZ, BD, PTSD, Depression, Borderline PD, Anxiety Disorders, ED, and ASD, making a well-replicated epigenetic transdiagnostic finding in psychiatry.
“There is extensive evidence of a difference in DNAm in BDNF, as well as EWAS studies showing enrichment for the neurogenesis pathway in SCZ (Di Carlo et al., 2019; Ursini et al., 2016), BD (Dell et al., 2014; Duffy et al., 2019), PTSD (Kim et al., 2017; Uddin et al., 2010), Depression (Hing, Sathyaputri, & Potash, 2018; Kang et al., 2015), Borderline PD (Arranz et al., 2021; Thomas et al., 2018),”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Dell et al., 2014
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- Authors
- Dell׳Osso, B., D׳Addario, C., Carlotta Palazzo, M., Benatti, B., Camuri, G., Galimberti, D., Fenoglio, C., Scarpini, E., Di Francesco, A., Maccarrone, M., & Carlo Altamura, A.
- Affiliations
- University of Milan (IT)
- Università Campus Bio-Medico (IT)
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 166
- Pages
- 330-333
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2063963078
- Cited by
- 112
- References
- 26
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 4 · 2023: 4 · 2022: 12 · 2021: 14 · 2020: 11 · 2019: 10 · 2018: 6 · 2017: 13 · 2016: 12 · 2015: 11 · 2014: 1
- FWCI
- 9.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- UniTERAMO Research Catalog (University of Teramo) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- brain-derived neurotrophic factor, DNA methylation, epigenetic regulation, bipolar disorder, bipolar I disorder, bipolar II disorder, major depressive disorder, mood disorders, lithium, valproic acid, peripheral blood mononuclear cells
- MeSH terms
- Adult, Aged, Bipolar Disorder, Cross-Sectional Studies, Major Depressive Disorder, Female, Humans, Leukocytes, Mononuclear, Male, Middle Aged, Promoter Regions, Genetic, Case-Control Studies, DNA Methylation, Brain-Derived Neurotrophic Factor, Epigenesis, Genetic
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