Transcriptomic and epigenomic biomarkers of antidepressant response

Belzeaux, Raoul; Lin, Rixing; Ju, Chelsey; Chay, Marc-Aurèle; Fiori, Laura M.; Lutz, Pierre-Eric; Turecki, Gustavo

doi:10.1016/j.jad.2017.08.087

Cited by 30 publications

(27 citation statements)

References 94 publications

(89 reference statements)

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“…Clearly miRNAs are responsive to AD treatment after ELS, but it is still not certain what mechanisms are responsible for this effect. No studies have directly investigated the effect of ADs on miRNA promoter region methylation after ELS, but there is a strong relationship between AD response and global methylation patterns [99]. Specific miRNA expression alterations have been associated with resistance to ADs treatment, but little more is known about the mechanism of this effect [100,101].…”

Section: Mirnas In Els-induced Depression and Schizophreniamentioning

confidence: 99%

MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior

2019

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Childhood environment can have a profound impact on brain structure and function. Epigenetic mechanisms have been shown to play a critical role in adaptive and maladaptive processes by regulating gene expression without changing the genome. Over the past few years, early life stress (ELS) has been established as a major risk factor for major depression and suicidal behavior along with other psychiatric illnesses in adulthood. In recent years, the emergence of small noncoding RNAs as a mega controller of gene expression has gained attention for their role in various disease processes. Among various noncoding RNAs, microRNAs (miRNAs) are the most studied and well characterized and have emerged as a major regulator of neural plasticity and higher brain functioning. More recently, although limited in number, studies are focusing on how miRNAs can play a role in the maladaptive processes associated with ELS both at adolescent and adult age and whether these processes are critical in developing depression and suicidal behavior. In this review, we critically evaluate how postnatal ELS relates to abnormalities in miRNA expression and functions from both animal and human literature and draw connections from these findings to depression and suicidal behavior later in life.

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Section: Mirnas In Els-induced Depression and Schizophreniamentioning

confidence: 99%

MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior

2019

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“…Furthermore, we need to consider that the individual variability to antidepressant response is also the consequence of an interplay between clinical factors and biological pathways, as well as with the environment [20]. For example, it has been clearly demonstrated that patients with a history of childhood trauma and other adversities, especially early in life, are also those with a low probability to respond to the first trials of antidepressant drugs or not respond at all to any kind of antidepressant therapy [5,6,7].…”

Section: Available Antidepressant Strategies and Current Biomarkers Omentioning

confidence: 99%

“…Biological fluids are the most practical tissues for patient sampling, particularly peripheral blood samples, as they are easy and quick to retrieve, although some limitations exist [27]. Moreover, blood samples allow simultaneously investigation of several different biomarkers, provide high concentrations and quality of DNA and RNA, and cellular components of peripheral blood (such as lymphocytes, monocytes and leukocytes) are suitable for functional studies [20].…”

Section: Available Antidepressant Strategies and Current Biomarkers Omentioning

confidence: 99%

“…weeks of paroxetine treatment. They showed that baseline levels of HDAC5 were significantly higher in drugfree depressed patients, an effect that was normalized by the pharmacological treatment [20,72].…”

Section: Dna Methylationmentioning

confidence: 99%

“…Histones undergo a number of different post-translational modifications that alter their interaction with DNA and nuclear proteins. The most common chemical modification is acetylation, which is catalyzed by histone acetyl-tranferase (HATs); other modifications include methylation, phosphorylation, ubiquitination, SUMOylation, citrullination and ADP-ribosylation[70].Several studies, using animal models or human post-mortem samples, have implicated histone modifications in the mechanisms underlying stress responses and the development of depressive phenotypes with the possibility that such changes can be normalized following antidepressant treatment (for a review see[20])…”

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confidence: 99%

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Blood biomarkers and treatment response in major depression

Mora

Zonca

Riva

et al. 2018

Expert Review of Molecular Diagnostics

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Millions of people worldwide suffer from depression, but despite advances in pharmacological therapies, many patients do not experience symptomatic remission or treatment response, even after treatments with several medications. As such, there is an urgent need to identify biomarkers that can not only predict the treatment response but also allow a rational selection of optimal therapy for each patient. Areas covered: This review examines the recent findings, coming from different 'omic sciences,' in human blood-based biomarkers associated with antidepressant treatment response with particular attention on genetic/epigenetic and biochemical biomarkers. Specific emphasis will be placed on key molecules related to neuroplasticity and inflammation because of their involvement in the pathophysiology of depression and antidepressant response. Expert commentary: Biomarker identification is still an ongoing work. Indeed, to date, no biomarkers have sufficiently proven specificity, sensitivity, and reproducibility to be used in the clinical setting. However, 'omic' approaches hold great promise in identifying multiple features for predicting antidepressant response, making a personalized treatment strategy possible for each patient, and thereby assist with quick and efficacious responsiveness. It is thus necessary that future studies take an integrative approach that includes clinical assessment, environment influences, and molecular and biological biomarkers.

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Suicide and suicide behaviors: A review of transcriptomics and multiomics studies in psychiatric disorders

Zhou

Lutz

Ibrahim

et al. 2018

J of Neuroscience Research

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Aberrant gene expression can contribute to brain and nervous system dysfunction that causes many psychiatric illnesses. Here, we review how transcriptomic approaches have deepened our understanding of the neurobiological underpinnings of psychiatric disorders and how they have to the identification of biomarkers for these disorders, with a focus on their relevance to suicide and suicide behaviors. We begin by providing an overview of the genetic, transcriptomic, and epigenetic factors (including non‐coding RNAs) implicated in suicide and their roles in the regulation of gene expression. Then, we highlight the unique benefits and limitations of using either postmortem brain or peripheral tissues in transcriptomic analyses. We examine the current shift from candidate gene to genome‐wide approaches in psychiatric research, which are concurrently emerging with the increased consideration of the Research Domain Criteria (RDoC) framework for classifying mental illnesses. Furthermore, we discuss the use of transcription networks and how they can be integrated into multiomic analyses. Finally, we end by highlighting recent findings of peripheral markers of suicide risk identified through the use of transcriptomic tools. Technological advancements and increased accessibility of these technologies are drastically shaping the current research landscape. We present an overview of the significant changes currently taking place to usher in a new era of psychiatric research.

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Transcriptomic and epigenomic biomarkers of antidepressant response

Cited by 30 publications

References 94 publications

MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior

MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior

Blood biomarkers and treatment response in major depression

Suicide and suicide behaviors: A review of transcriptomics and multiomics studies in psychiatric disorders

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