Anticipated brain molecular aging in major depression
Open accessAbstract
Objectives Brain molecular aging, the pervasive and consistent transcriptome changes associated with normal brain aging, appears to overlap with disease pathways and may be anticipated in neurodegenerative and neuropsychiatric diseases, including major depressive disorder (MDD). Here, we characterize the global interaction of MDD-related gene changes with age, starting from our previous report of downregulated brain-derived neurotrophic factor (BDNF) and BDNF-dependent genes in the amygdala of women with MDD.Methods A large-scale gene expression data set in the amygdala from a postmortem cohort of 21 women with MDD and 21 age-matched controls (age range: 16-74 years) was analyzed for correlations of gene transcript changes with age, in the presence or absence of a diagnosis of MDD.Results 1) The age-related decrease in BDNF transcripts observed in control subjects corresponds with further age-related decreases in BDNF and BDNF-dependent gene expression in MDD subjects; 2) most MDD-related genes are frequently age-regulated in both MDD and control subjects; 3) the effects of MDD and age are positively correlated; 4) most genes that are age-dependent in control subjects display greater age effects in MDD subjects; and 5) the increased prevalence of age effects in MDD corresponds to similar trends in controls, rather than representing de novo age effects.Conclusions MDD strongly associates with robust and anticipated gene expression changes that occur during normal aging of the brain, suggesting that an older molecular age of the brain represents an early biological event and/or a marker of risk for subsequent onset of MDD symptoms.
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MDD has been associated with neuroanatomic/neurodevelopmental as well as brain transcriptome evidence of accelerated brain aging.
“Further, MDD has been associated with neuroanatomic/neurodevelopmental as well as brain transcriptome evidence of accelerated brain aging (Douillard-Guilloux et al., 2013; Koutsouleris et al., 2014).”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Douillard-Guilloux et al., 2013
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- Authors
- Douillard-Guilloux, G., Guilloux, J.-P., Lewis, D. A., & Sibille, E.
- Affiliations
- Université Paris-Sud (FR)
- University of Pittsburgh (US)
- Corresponding author
- Sibille, Etienne
- Venue
- The American Journal of Geriatric Psychiatry
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 21
- Issue
- 5
- Pages
- 450-460
- ISSN
- 1064-7481 (ISSN-L)
- PMC
- PMC3615087
- OpenAlex
- W2134065798
- Cited by
- 62
- References
- 29
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 7 · 2015: 7 · 2014: 5 · 2013: 7 · 2012: 1
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000005)
- National Institute of Mental Health (P50MH084053, MH084060, MH-093723, MH084053, R01MH043784, R01MH093723, R01MH077159, K02MH084060, R37MH043784, MH043784)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- major depressive disorder, brain aging, gene expression, amygdala, brain-derived neurotrophic factor, transcriptome, postmortem brain, women, age-related gene expression, risk indicators
- MeSH terms
- Adolescent, Adult, Aged, Aging, Amygdala, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Middle Aged, Biomarkers, Case-Control Studies, Brain-Derived Neurotrophic Factor, Genetic Predisposition to Disease
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