Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression
Abstract
Epidemiological studies have shown significant results in the interaction between the functions of brain-derived neurotrophic factor (BDNF) and 5-HT in mood disorders, such as major depressive disorder (MDD). The latest research has provided convincing evidence that gene transcription of these molecules is a target for epigenetic changes, triggered by stressful stimuli that starts in early childhood and continues throughout life, which are subsequently translated into structural and functional phenotypes culminating in depressive disorders. The short variants of 5-HTTLPR and BDNF-Met are seen as forms which are predisposed to epigenetic aberrations, which leads individuals to a susceptibility to environmental adversities, especially when subjected to stress in early life. Moreover, the polymorphic variants also feature epistatic interactions in directing the functional mechanisms elicited by stress and underlying the onset of depressive disorders. Also emphasized are works which show some mediators between stress and epigenetic changes of the 5-HTT and BDNF genes, such as the hypothalamic-pituitary-adrenal (HPA) axis and the cAMP response element-binding protein (CREB), which is a cellular transcription factor. Both the HPA axis and CREB are also involved in epistatic interactions between polymorphic variants of 5-HTTLPR and Val66Met. This review highlights some research studying changes in the epigenetic patterns intrinsic to genes of 5-HTT and BDNF, which are related to lifelong environmental adversities, which in turn increases the risks of developing MDD.
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Chronic stress throughout life involves biological changes that underlie MDD in many patients and in laboratory animals.
“Chronic stress throughout life involves several biological changes, which are underlying MDD in many patients and in laboratory animals [4],[6],[9].”
From Stress and serum cortisol levels in major depressive disorder: a cross-sectional study (2020) · cites this paper as [6]
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- Authors
- Ignácio, Z. M., Réus, G. Z., Abelaira, H. M., & Quevedo, J.
- Affiliations
- Universidade Federal da Fronteira Sul (BR)
- Universidade do Extremo Sul Catarinense (BR)
- Corresponding author
- Réus, G.Z.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 275
- Pages
- 455-468
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2020644015
- Cited by
- 65
- References
- 19
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 14 · 2015: 9 · 2014: 4
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- CNPq
- FAPESC
- Instituto Cérebro e Mente
- UNESC
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- serotonin transporter, 5-HTTLPR, brain-derived neurotrophic factor, BDNF Val66Met polymorphism, major depressive disorder, epigenetic regulation, epistasis, childhood adversity, early life stress, hypothalamic-pituitary-adrenal axis, CREB, gene-environment interaction, depression risk
- MeSH terms
- Depression, Epistasis, Genetic, Gene Expression Regulation, Humans, Brain-Derived Neurotrophic Factor, Polymorphism, Single Nucleotide, Epigenesis, Genetic, Serotonin Plasma Membrane Transport Proteins
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