Epigenetics, a key for unlocking complex CNS disorders? Therapeutic implications
Abstract
Aberrant changes in gene function are believed to be involved in a wide spectrum of human disease including behavioral, cognitive and neurodegenerative pathologies. Most of the attention in last few decades have focused on changes in gene sequence as a cause of gene dysfunction leading to disease and mental health disorders. Germ line mutations or other alterations in the sequence of DNA that associate with different behavioral and neurological pathologies have been identified. However, sequence alterations explain only a small fraction of the cases. In addition there is evidence for "gene-environment" interactions in the brain suggesting mechanisms that alter gene function and the phenotype through environmental exposure. Genes are programmed by "epigenetic" mechanisms such as chromatin structure, chromatin modification and DNA methylation. These mechanisms confer on similar sequences different identities during cellular differentiation. Epigenetic differences are proposed to be involved in differentiating gene function in response to different environmental contexts and could result in alterations in functional gene networks that lead to brain disease. Epigenetic markers could serve important biomarkers in brain and behavioral diseases. Moreover, epigenetic processes are potentially reversible pointing to epigenetic therapeutics in psychotherapy.
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Clinical application of epigenetic drugs is still a long way off, and several caveats such as the lack of selectivity and specificity of currently available agents remain.
“Yet, clinical application is still a long way off, and several caveats such as the lack of selectivity and specificity of currently available agents remain (see Szyf, 2015).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Szyf, 2015
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Tomppo, L., Hennah, W., Lahermo, P., Loukola, A., Tuulio‐Henriksson, A., Suvisaari, J., Partonen, T., Ekelund, J., Lönnqvist, J. K., & Peltonen, L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.01.014 · Cited by 84 · see citing works
Presenilin-1 Mutations in Alzheimer's Disease: An Update on Genotype-Phenotype Relationships
Larner, A. J. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130746 · Cited by 83 · see citing works
Circulating microRNAs in Alzheimer’s disease: the search for novel biomarkers
Dorval, V., Nelson, P. T., & Hébert, S. S. (2013) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2013.00024 · Cited by 80 · see citing works
Autism genetics: emerging data from genome-wide copy-number and single nucleotide polymorphism scans
Weiss, L. A. (2009) · Expert Review of Molecular Diagnostics · doi:10.1586/erm.09.59 · Cited by 80 · see citing works
Rat transgenic models with a phenotype of intracellular Aβ accumulation in hippocampus and cortex
Echeverrı́a, V., Ducatenzeiler, A., Alhonen, L. I., Jänne, J., Grant, S. M., Wandosell, F. G., Muro, A. F., Baralle, F. E., Li, H., Duff, K., et al. (2004) · Journal of Alzheimer s Disease · doi:10.3233/jad-2004-6301 · Cited by 77 · see citing works
Self-citationBrown, S. E., Weaver, I. C. G., Meaney, M. J., & Moshe Szyf, A. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.05.028 · Cited by 77 · see citing works
Garcia-Linares, M. I., Sánchez-Lorente, S., Coe, C. L., & Martı́nez, M. (2004) · Psychosomatic Medicine · doi:10.1097/01.psy.0000145820.90041.c0 · Cited by 76 · see citing works
Child care setting affects salivary cortisol and antibody secretion in young children
Watamura, S. E., Coe, C. L., Laudenslager, M. L., & Robertson, S. S. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.02.001 · Cited by 76 · cited 2× · see citing works
“The response of the peripheral immune system to social adversity signals should not be surprising, as decades of studies have delineated bilateral relationship between the HPA axis and the immune system as well as between the immune system and brain function(Bellinger et al., 2008; Buske-Kirschbaum, 2009; Coe and Eric…”
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Toward understanding how early-life stress reprograms cognitive and emotional brain networks
Chen, Y., & Baram, T. Z. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.181 · Cited by 474 · see citing works
The epigenetics of aging and neurodegeneration
Lardenoije, R., Iatrou, A., Kenis, G., Kompotis, K., Steinbusch, H. W. M., Mastroeni, D., Coleman, P., Lemere, C. A., Hof, P. R., van den Hove, D. L. A., et al. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.05.002 · Cited by 381 · see citing works
Schiele, M. A., Gottschalk, M. G., & Domschke, K. (2020) · Clinical Psychology Review · doi:10.1016/j.cpr.2020.101830 · Cited by 156 · see citing works
Millan, M. J., Goodwin, G. M., Meyer-Lindenberg, A., & Ove Ögren, S. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.01.016 · Cited by 132 · see citing works
Tyrka, A. R., Ridout, K. K., & Parade, S. H. (2016) · Development and Psychopathology · doi:10.1017/s0954579416000870 · Cited by 119 · see citing works
Aligning physiology with psychology: Translational neuroscience in neuropsychiatric drug discovery
McArthur, R. A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.02.004 · Cited by 42 · see citing works
- Authors
- Szyf, M.
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 25
- Issue
- 5
- Pages
- 682-702
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W1985697930
- Cited by
- 76
- References
- 248
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 14 · 2022: 2 · 2021: 2 · 2020: 7 · 2019: 8 · 2018: 2 · 2017: 8 · 2016: 9 · 2015: 7 · 2014: 3
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- epigenetics, central nervous system disorders, chromatin modification, DNA methylation, gene-environment interaction, epigenetic biomarkers, epigenetic therapy, neurodegenerative diseases, mental illness, chromatin structure, cell differentiation
- MeSH terms
- Animals, Central Nervous System Agents, Central Nervous System Diseases, Humans, Epigenesis, Genetic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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