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Epigenetic Research in Neuropsychiatric Disorders: the “Tissue Issue”
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Purpose of review Evidence has linked neuropsychiatric disorders with epigenetic marks as either a biomarker of disease, biomarker of exposure, or mechanism of disease processes. Neuropsychiatric epidemiologic studies using either target brain tissue or surrogate blood tissue each have methodological challenges and distinct advantages.Recent findings Brain tissue studies are challenged by small sample sizes of cases and controls, incomplete phenotyping, post-mortem timing, and cellular heterogeneity, but the use of a primary disease relevant tissue is critical. Blood-based studies have access to much larger sample sizes and more replication opportunities, as well as the potential for longitudinal measurements, both prior to onset and during the course of treatments. Yet, blood studies also are challenged by cell-type heterogeneity, and many question the validity of using peripheral tissues as a brain biomarker. Emerging evidence suggests that these limitations to blood-based epigenetic studies are surmountable, but confirmation in target tissue remains important.Summary Epigenetic mechanisms have the potential to help elucidate biology connecting experiential risk factors with neuropsychiatric disease manifestation. Cross-tissue studies as well as advanced epidemiologic methods should be employed to more effectively conduct neuropsychiatric epigenetic research.
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“Human studies to assess epigenetic modifications have been lim ited to measures made in blood cells or in post- mortem brain 115,116 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [116]
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“Elucidating molecular changes in the human brain is made difficult by the timing of sample acquisition, cell type distribution between samples, cause of death, and brain agonal state, as well as sample handling, storage temperatures, and sample size (Bakulski et al., 2016).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Bakulski et al., 2016
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“epigenetic studies so far have mostly (with the exception of investigations in post-mortem samples) relied on peripheral tissues, which precludes definite conclusions from being drawn regarding CNS processes.”
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 Bakulski, Halladay, Hu, Mill, & Fallin, 2016
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Metadata
- Authors
- Bakulski, K. M., Halladay, A., Hu, V. W., Mill, J., & Fallin, M. D.
- Affiliations
- University of Michigan (US)
- Rutgers, The State University of New Jersey (US)
- George Washington University (US)
- King's College London (GB)
- Johns Hopkins University (US)
- Corresponding author
- Fallin, M. Daniele
- Venue
- Current Behavioral Neuroscience Reports
- Published
- 2016-08-02
- Volume
- 3
- Issue
- 3
- Pages
- 264-274
- ISSN
- 2196-2979 (ISSN-L)
- PMC
- PMC5235359
- OpenAlex
- W2505166506
- Cited by
- 127
- References
- 111
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 12 · 2023: 13 · 2022: 25 · 2021: 13 · 2020: 15 · 2019: 11 · 2018: 14 · 2017: 12
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Behavioral Neuroscience Reports (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (ES017646, ES023061)
- Medical Research Council (MRC; MR/K013807/1)
- National Institutes of Health (AG036039)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Keywords
- epigenetics, neuropsychiatric disorders, blood-based biomarkers, brain tissue, surrogate tissue, cellular heterogeneity, postmortem brain, risk factors
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