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Curr Behav Neurosci Rep. 2016 Sep;3(3):264-274. doi: 10.1007/s40473-016-0083-4. Epub 2016 Aug 2.

Epigenetic Research in Neuropsychiatric Disorders: the "Tissue Issue".

Author information

1
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
2
Autism Science Foundation, New York City, New York, USA; Department of Pharmacology and Toxicology, Rutgers University, New Brunswick, New Jersey, USA.
3
Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
4
University of Exeter Medical School, University of Exeter, Exeter, UK; Institute for Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
5
Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA; Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Abstract

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.

KEYWORDS:

Blood; DNA methylation; Epigenetics; Neuropsychiatric disorders; Tissue

Conflict of interest statement

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.

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