Epigenetic Modifications of Major Depressive Disorder

Saavedra, Kathleen; Molina-Márquez, Ana; Saavedra, Nicolás; Zambrano, Tomás; Salazar, Luis A.

doi:10.3390/ijms17081279

Cited by 93 publications

(63 citation statements)

References 129 publications

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“…Both these medications are epigenetic modifiers which elicit potent effects on genome-wide gene expression (Covington et al, 2009). There is a considerable body of evidence which reveals epigenetic differences between MDD cases and controls (Saavedra et al, 2016). Furthermore, recent results from the genetic pathway analysis of an MDD genome-wide association study, suggest that genes regulating epigenetic modifications of histones might be causally related to MDD (The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium, 2015).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning

et al. 2017

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Current pharmacological treatments for major depressive disorder (MDD) are ineffective in a significant proportion of patients, and the identification of new antidepressant compounds has been difficult. ‘Connectivity mapping’ is a method that can be used to identify drugs that elicit similar downstream effects on mRNA levels when compared to current treatments, and thus may point towards possible repositioning opportunities. We investigated genome-wide transcriptomic changes to human hippocampal progenitor cells treated with therapeutically relevant concentrations of a tricyclic antidepressant (nortriptyline) and a selective serotonin reuptake inhibitor (escitalopram). We identified mRNA changes common to both drugs to create an ‘antidepressant mRNA signature’. We used this signature to probe the Library of Integrated Network-based Cellular Signatures (LINCS) and to identify other compounds that elicit similar changes to mRNA in neural progenitor cells. Results from LINCS revealed that the tricyclic antidepressant clomipramine elicited mRNA changes most similar to our mRNA signature, and we identified W-7 and vorinostat as functionally relevant drug candidates, which may have repositioning potential. Our results are encouraging and represent the first attempt to use connectivity mapping for drug repositioning in MDD.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning

et al. 2017

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“…The recent advancement in epigenome‐wide analyses has advanced the field beyond a gene‐candidate approach towards a more comprehensive mapping of the neuroepigenome. In this regard, life exposure‐ and phenotype‐specific epigenome signatures are constantly being generated, as in the case of childhood maltreatment, MDD, BD, SCZ, autism spectrum disorder, eating disorders and shared features, such as suicidality or psychosis . These epigenomic studies have uncovered dysregulation of multiple biological pathways, including the previously identified HPA, monoaminergic, and neurotrophin systems.…”

Section: Potential Use Of Epigenetics For Mechanistic Insight and Novmentioning

confidence: 99%

Epigenetics applied to psychiatry: Clinical opportunities and future challenges

Kular

2018

Psychiatry Clin Neurosci

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Psychiatric disorders are clinically heterogeneous and debilitating chronic diseases resulting from a complex interplay between gene variants and environmental factors. Epigenetic processes, such as DNA methylation and histone posttranslational modifications, instruct the cell/tissue to correctly interpret external signals and adjust its functions accordingly. Given that epigenetic modifications are sensitive to environment, stable, and reversible, epigenetic studies in psychiatry could represent a promising approach to better understanding and treating disease. In the present review, we aim to discuss the clinical opportunities and challenges arising from the epigenetic research in psychiatry. Using selected examples, we first recapitulate key findings supporting the role of adverse life events, alone or in combination with genetic risk, in epigenetic programming of neuropsychiatric systems. Epigenetic studies further report encouraging findings about the use of methylation changes as diagnostic markers of disease phenotype and predictive tools of progression and response to treatment. Then we discuss the potential of using targeted epigenetic pharmacotherapy, combined with psychosocial interventions, for future personalized medicine for patients. Finally, we review the methodological limitations that could hinder interpretation of epigenetic data in psychiatry. They mainly arise from heterogeneity at the individual and tissue level and require future strategies in order to reinforce the biological relevance of epigenetic data and its translational use in psychiatry. Overall, we suggest that epigenetics could provide new insights into a more comprehensive interpretation of mental illness and might eventually improve the nosology, treatment, and prevention of psychiatric disorders.

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“…DNA methylation, histone alteration and miRNA expression changes are greatly involved in the disruption and dysregulation of gene expression in depression. Better understanding of the mechanisms of depression pathogenesis opens doors to improved diagnosis and specific targeted treatment [38] [43].…”

Section: Mddmentioning

confidence: 99%

Epigenetics and Depression: A Rabbit Hole of Discovery

Pace¹,

Blundell²

2018

OJGen

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"After this, there is no turning back. You take the blue pill-the story ends, you wake up in your bed and believe whatever you want to believe. You take the red pill-you stay in Wonderland, and I show you how deep the rabbit hole goes. Remember: all I'm offering is the truth." Epigenetics is a bit like the red pill-the more it is researched the further down the rabbit hole we are going-the realisation that my choices today as my parents' and grandparents' choices yesterday influence who I am now and who I am going to be tomorrow. Through the study of gene influencers, scientists are discovering that it is not only the DNA that makes us but which portion of is selected for use that tells us who we are. In the field of depression, epigenetics is still in its infancy, nonetheless significant connections have been uncovered. This paper gives a brief overview on epigenetics and the different mechanisms correlated with it. It also discusses factors affecting an individual's epigenetic patterns and the effect of epigenetics itself. It specifically delves into the epigenetic effects on psychiatry, mainly depression, depressive symptoms and antidepressant treatments and the mediation of mechanism of action of the epigenetic modifications involved.

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Epigenetic Modifications of Major Depressive Disorder

Cited by 93 publications

References 129 publications

Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning

Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning

Epigenetics applied to psychiatry: Clinical opportunities and future challenges

Epigenetics and Depression: A Rabbit Hole of Discovery

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