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.
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.
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.
KeywordsNeuropsychiatric disorders DNA methylation Epigenetics Tissue Blood
Compliance with Ethical Standards
Conflict of Interest
Dr. Kelly M. Bakulski, Dr. Alycia Halladay, Dr. Valerie W. Hu, Dr. Jonathan Mill, and Dr. M. Daniele Fallin declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Drs. Bakulski and Fallin were supported by the National Institute of Environmental Health Sciences (ES017646). Dr. Hu was supported by the National Institute of Environmental Health Sciences (ES023061). Dr. Mill was supported by the UK Medical Research Council (MRC; MR/K013807/1) and the US National Institutes of Health (AG036039).
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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