Laura M Hack1, Gabriel R Fries2, Harris A Eyre3, Chad A Bousman4, Ajeet B Singh5, Joao Quevedo2, Vineeth P John2, Bernhard T Baune6, Boadie W Dunlop7. 1. Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Palo Alto, CA 94305, USA; Sierra Pacific Mental Illness Research Education and Clinical Centers, VA Palo Alto Health Care System, Palo Alto, CA, USA. Electronic address: lhack@stanford.edu. 2. Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. 3. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Palo Alto, CA 94305, USA; Innovation Institute, Texas Medical Center, Houston, TX, USA; IMPACT SRC, School of Medicine, Deakin University, Geelong, Victoria, Australia; Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia. 4. Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada. 5. IMPACT SRC, School of Medicine, Deakin University, Geelong, Victoria, Australia. 6. Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia. 7. Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA, USA.
Abstract
BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide, and over half of patients do not achieve symptom remission following an initial antidepressant course. Despite evidence implicating a strong genetic basis for the pathophysiology of MDD, there are no adequately validated biomarkers of treatment response routinely used in clinical practice. Pharmacoepigenetics is an emerging field that has the potential to combine both genetic and environmental information into treatment selection and further the goal of precision psychiatry. However, this field is in its infancy compared to the more established pharmacogenetics approaches. METHODS: We prepared a narrative review using literature searches of studies in English pertaining to pharmacoepigenetics and treatment of depressive disorders conducted in PubMed, Google Scholar, PsychINFO, and Ovid Medicine from inception through January 2019. We reviewed studies of DNA methylation and histone modifications in both humans and animal models of depression. RESULTS: Emerging evidence from human and animal work suggests a key role for epigenetic marks, including DNA methylation and histone modifications, in the prediction of antidepressant response. The challenges of heterogeneity of patient characteristics and loci studied as well as lack of replication that have impacted the field of pharmacogenetics also pose challenges to the development of pharmacoepigenetic tools. Additionally, given the tissue specific nature of epigenetic marks as well as their susceptibility to change in response to environmental factors and aging, pharmacoepigenetic tools face additional challenges to their development. LIMITATIONS: This is a narrative and not systematic review of the literature on the pharmacoepigenetics of antidepressant response. We highlight key studies pertaining to pharmacoepigenetics and treatment of depressive disorders in humans and depressive-like behaviors in animal models, regardless of sample size or methodology. While we discuss DNA methylation and histone modifications, we do not cover microRNAs, which have been reviewed elsewhere recently. CONCLUSIONS: Utilization of genome-wide approaches and reproducible epigenetic assays, careful selection of the tissue assessed, and integration of genetic and clinical information into pharmacoepigenetic tools will improve the likelihood of developing clinically useful tests.
BACKGROUND:Major depressive disorder (MDD) is a leading cause of disability worldwide, and over half of patients do not achieve symptom remission following an initial antidepressant course. Despite evidence implicating a strong genetic basis for the pathophysiology of MDD, there are no adequately validated biomarkers of treatment response routinely used in clinical practice. Pharmacoepigenetics is an emerging field that has the potential to combine both genetic and environmental information into treatment selection and further the goal of precision psychiatry. However, this field is in its infancy compared to the more established pharmacogenetics approaches. METHODS: We prepared a narrative review using literature searches of studies in English pertaining to pharmacoepigenetics and treatment of depressive disorders conducted in PubMed, Google Scholar, PsychINFO, and Ovid Medicine from inception through January 2019. We reviewed studies of DNA methylation and histone modifications in both humans and animal models of depression. RESULTS: Emerging evidence from human and animal work suggests a key role for epigenetic marks, including DNA methylation and histone modifications, in the prediction of antidepressant response. The challenges of heterogeneity of patient characteristics and loci studied as well as lack of replication that have impacted the field of pharmacogenetics also pose challenges to the development of pharmacoepigenetic tools. Additionally, given the tissue specific nature of epigenetic marks as well as their susceptibility to change in response to environmental factors and aging, pharmacoepigenetic tools face additional challenges to their development. LIMITATIONS: This is a narrative and not systematic review of the literature on the pharmacoepigenetics of antidepressant response. We highlight key studies pertaining to pharmacoepigenetics and treatment of depressive disorders in humans and depressive-like behaviors in animal models, regardless of sample size or methodology. While we discuss DNA methylation and histone modifications, we do not cover microRNAs, which have been reviewed elsewhere recently. CONCLUSIONS: Utilization of genome-wide approaches and reproducible epigenetic assays, careful selection of the tissue assessed, and integration of genetic and clinical information into pharmacoepigenetic tools will improve the likelihood of developing clinically useful tests.
Authors: A John Rush; Madhukar H Trivedi; Stephen R Wisniewski; Andrew A Nierenberg; Jonathan W Stewart; Diane Warden; George Niederehe; Michael E Thase; Philip W Lavori; Barry D Lebowitz; Patrick J McGrath; Jerrold F Rosenbaum; Harold A Sackeim; David J Kupfer; James Luther; Maurizio Fava Journal: Am J Psychiatry Date: 2006-11 Impact factor: 18.112
Authors: Daniel N Klein; Bruce A Arnow; Jennifer L Barkin; Frank Dowling; James H Kocsis; Andrew C Leon; Rachel Manber; Barbara O Rothbaum; Madhukar H Trivedi; Stephen R Wisniewski Journal: Depress Anxiety Date: 2009 Impact factor: 6.505