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.
Global and Site-Specific Changes in 5-Methylcytosine and 5-Hydroxymethylcytosine after Extended Post-mortem Interval.Front Genet. 2016 Jun 23;7:120. doi: 10.3389/fgene.2016.00120. eCollection 2016. Front Genet. 2016. PMID: 27446202 Free PMC article.
[Epigenetics of schizophrenia: a review].Encephale. 2014 Oct;40(5):380-6. doi: 10.1016/j.encep.2014.06.005. Epub 2014 Aug 12. Encephale. 2014. PMID: 25127897 Review. French.
Alterations in DNA methylation of Fkbp5 as a determinant of blood-brain correlation of glucocorticoid exposure.Psychoneuroendocrinology. 2014 Jun;44:112-22. doi: 10.1016/j.psyneuen.2014.03.003. Epub 2014 Mar 20. Psychoneuroendocrinology. 2014. PMID: 24767625 Free PMC article.
DNA methylation of BDNF as a biomarker of early-life adversity.Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):6807-13. doi: 10.1073/pnas.1408355111. Epub 2014 Nov 10. Proc Natl Acad Sci U S A. 2015. PMID: 25385582 Free PMC article.
Repetitive elements and epigenetic marks in behavior and psychiatric disease.Adv Genet. 2014;86:185-252. doi: 10.1016/B978-0-12-800222-3.00009-7. Adv Genet. 2014. PMID: 25172351 Review.
Cited by 18 articles
Towards a Multivariate Biomarker-Based Diagnosis of Autism Spectrum Disorder: Review and Discussion of Recent Advancements.Semin Pediatr Neurol. 2020 Jul;34:100803. doi: 10.1016/j.spen.2020.100803. Epub 2020 Mar 5. Semin Pediatr Neurol. 2020. PMID: 32446437 Review.
Antipsychotic Medications and DNA Methylation in Schizophrenia and Bipolar Disorder: A Systematic Review.Pharmacotherapy. 2020 Apr;40(4):331-342. doi: 10.1002/phar.2375. Epub 2020 Mar 9. Pharmacotherapy. 2020. PMID: 32058614
Genomic Tools for Environmental Epigenetics and Implications for Public Health.Curr Opin Toxicol. 2019 Dec;18:27-33. doi: 10.1016/j.cotox.2019.02.008. Epub 2019 Mar 8. Curr Opin Toxicol. 2019. PMID: 31763499
Systematic evaluation and validation of reference and library selection methods for deconvolution of cord blood DNA methylation data.Clin Epigenetics. 2019 Aug 27;11(1):125. doi: 10.1186/s13148-019-0717-y. Clin Epigenetics. 2019. PMID: 31455416 Free PMC article.
Epigenetic pharmacotherapy for substance use disorder.Biochem Pharmacol. 2019 Oct;168:269-274. doi: 10.1016/j.bcp.2019.07.012. Epub 2019 Jul 12. Biochem Pharmacol. 2019. PMID: 31306644 Review.