The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities
Open accessAbstract
Monoamine oxidase A (MAOA) harbours a polymorphic upstream variable-number tandem repeat (u-VNTR). The MAOA-L allele of the u-VNTR leads to decreased gene expression levels in vitro and has been found to increase the risk of conduct disorder in males with childhood adversities. Early-life adversities have been associated with hypermethylation of the glucocorticoid receptor (NR3C1). In this study, we first performed a genetic association analysis of the MAOA u-VNTR using individuals with depression (n = 392) and controls (n = 1276). Next, DNA methylation analyses of MAOA and NR3C1 were performed using saliva samples of depressed and control subgroups. Adult MAOA-L females with childhood adversities were found to have a higher risk of developing depression (p = 0.006) and overall MAOA methylation levels were decreased in depressed females compared to controls (mean depressed, 42% vs. mean controls, 44%; p = 0.04). One specific childhood adversity [early parental death (EPD)] was associated with hypermethylation of NR3C1 close to an NGFI-A binding site (mean EPD, 19% vs. mean non-EPD, 14%; p = 0.005). Regression analysis indicated that this association may be mediated by the MAOA-L allele (adjusted R2 = 0.24, ANOVA: F = 23.48, p < 0.001). Conclusively: (1) depression in females may result from a gene × childhood-adversity interaction and/or a dysregulated epigenetic programming of MAOA; (2) childhood-adversity subtypes may differentially impact DNA methylation at NR3C1; (3) baseline MAOA-genotypic variations may affect the extent of NR3C1 methylation.
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“and the overall methylation of MAOA was reduced in depressed patients (130).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [130]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Lower MAOA activity, which is associated with higher levels of the relevant neurotransmitters, has been associated with increased risk of conduct disorder and antisocial behavior (130, 131).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [130]
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“carriers of the lower-MAOA-activity variants (i.e., the higher risk alleles such as 3.5) had a higher risk of depression with histories of childhood trauma in females compared to those who without trauma histories”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [130]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“A variant in MAOA gene is associated with differential NR3C1 methylation (130).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [130]
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“one specific type of childhood trauma (parental death) was associated with hypermethylation of the NR3C1 CpGs close to the NGFI-A binding site, at, in association with the L-allele (3.5 repeats) of the MAOA u-VNTR in salivary DNA samples (130).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [130]
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“the lower-activity MAOA-allele (3.5 repeats) of the MAOA u-VNTR has been associated with other epigenetic modifications, such as NR3C1 hypermethylation after childhood trauma (130).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [130]
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“Although some studies presented in this review have found evidence that some genotypic variation in some risk alleles can influence DNAm (Klengel et al., 2013; Melas et al., 2013; Perroud et al., 2016)”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Melas et al., 2013
In the citing paper
“In this study, and others132 childhood parental loss was associated with increased methylation of the exon 1F NR3C1 gene promoter”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [132]
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Cites
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MethodEpigenetic programming by maternal behavior
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Turecki, G., & Meaney, M. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.11.022 · Cited by 796
Pathophysiological mechanisms implicated in postpartum depression
Payne, J. L., & Maguire, J. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.12.001 · Cited by 459
Smith, A. K., Kilaru, V., Klengel, T., Mercer, K. B., Bradley, B., Conneely, K. N., Ressler, K. J., & Binder, E. B. (2015) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32278 · Cited by 355
Palma-Gudiel, H., Córdova-Palomera, A., Leza, J. C., & Fañanás, L. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.016 · Cited by 347
The Consequences of Early‐Life Adversity: Neurobiological, Behavioural and Epigenetic Adaptations
Maccari, S., Krugers, H. J., Morley‐Fletcher, S., Szyf, M., & Brunton, P. J. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12175 · Cited by 367
Metadata
- Authors
- Melas, P. A., Wei, Y., Wong, C. C. Y., Sjöholm, L. K., Åberg, E., Mill, J., Schalling, M., Forsell, Y., & Lavebratt, C.
- Affiliations
- Karolinska University Hospital (SE)
- Department of Molecular Medicine and Surgery, Neurogenetics Unit, Karolinska Institutet, Stockholm, Sweden
- King's College London (GB)
- Karolinska Institutet (SE)
- Corresponding author
- Lavebratt, Catharina
- ORCID
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-08-01
- Volume
- 16
- Issue
- 7
- Pages
- 1513-1528
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2008523946
- Cited by
- 220
- References
- 78
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 11 · 2023: 14 · 2022: 17 · 2021: 18 · 2020: 23 · 2019: 16 · 2018: 22 · 2017: 24 · 2016: 20 · 2015: 21 · 2014: 20 · 2013: 3
- FWCI
- 9.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Bodossaki Foundation
- Karolinska Institutet
- Stockholms Läns Landsting
- Vetenskapsrådet (2010-03631, 2008-03307, 2009-05546, 2011-04807)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- monoamine oxidase A, NR3C1, glucocorticoid receptor, DNA methylation, depression, childhood adversity, gene-environment interaction, epigenetic programming, sex differences
- MeSH terms
- Adult, Aged, Child, Depression, Environment, Female, Humans, Life Change Events, Male, Middle Aged, Monoamine Oxidase, Receptors, Glucocorticoid, Sex Factors, Chi-Square Distribution, Minisatellite Repeats, CpG Islands, DNA Methylation, Genetic Association Studies, Epigenomics
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