Genes and Biomarkers of Mood and Anxiety Disorders

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 27025

Special Issue Editors


E-Mail Website
Guest Editor
Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy
Interests: RNA metabolism; gene expression; transcriptomic; mood disorders

E-Mail Website
Guest Editor
Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Interests: psychiatric genetics; schizophrenia; mood disorders; genomics; transcriptomic

Special Issue Information

Dear Colleagues,

By 2020, mental health disorders will surpass all physical diseases as a major cause of disability. One in four people, about 450 million people worldwide, suffers from mental disorders in both developed and developing countries; in particular, major depressive disorder (MDD) and anxiety disorders (ADs) are among the most common mental disorders with a lifetime prevalence ranging from 12% to more than 20%.

Anxiety and depression share a long, close history in psychiatric nosology and treatment. In addition, recent genetic studies have revealed that MDD and ADs are complex, heritable phenotypes with intriguing genetic correlations. Given the prevalence and the immense social and economic burden of these disorders, it is of strong interest to find biomarkers helping to improve diagnosis, prognosis, and accelerate the drug discovery process.

A biomarker is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention”, including genomics, epigenomics, transcriptomics, and proteomic profiles. The evidence to date suggests that biomarkers reflecting the activity of neurotrophic, neurotransmitter, neuroendocrine, inflammatory, and metabolic systems may be able to predict mental and physical health outcomes in currently depressed individuals. However, there is much inconsistency in the findings.

For this Special Issue, we would like to invite reviews, perspectives, and research papers that highlight the most recent and significant advances in this field, as well as indicate new research frontiers.

Prof. Alessandro Barbon
Prof. Chiara Magri
Guest Editors

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Keywords

  • Mood disorders
  • Major depressive disorder
  • Anxiety disorders
  • Biomarkers
  • Multi “omics” analyses
  • Animal models
  • Heritability
  • Drug discovery

Published Papers (5 papers)

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Research

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14 pages, 1506 KiB  
Article
Enrichment Environment Positively Influences Depression- and Anxiety-Like Behavior in Serotonin Transporter Knockout Rats through the Modulation of Neuroplasticity, Spine, and GABAergic Markers
by Giulia Sbrini, Paola Brivio, Kari Bosch, Judith Regina Homberg and Francesca Calabrese
Genes 2020, 11(11), 1248; https://doi.org/10.3390/genes11111248 - 23 Oct 2020
Cited by 18 | Viewed by 2624
Abstract
The serotonin transporter (5-HTT in humans, SERT in rodents) is the main regulator of serotonergic transmission in the brain. The short allelic variant of the 5-HTT gene is in humans associated with psychopathologies and may enhance the vulnerability to develop depression after exposure [...] Read more.
The serotonin transporter (5-HTT in humans, SERT in rodents) is the main regulator of serotonergic transmission in the brain. The short allelic variant of the 5-HTT gene is in humans associated with psychopathologies and may enhance the vulnerability to develop depression after exposure to stressful events. Interestingly, the short allele also increases the sensitivity to a positive environment, which may buffer the vulnerability to depression. Since this polymorphism does not exist in rodents, male SERT knockout (SERT−/−) rats were tested to explore the molecular mechanisms based on this increased predisposition. This article investigates the influences of a positive manipulation, namely, enriched environment (EE), on the depressive-like behavior observed in SERT−/− rats. We found that one month of EE exposure normalized the anhedonic and anxious-like phenotype characteristics of this animal model. Moreover, we observed that EE exposure also restored the molecular alterations in the prefrontal cortex by positively modulating the expression of the neurotrophin Bdnf, and of spines and gamma-aminobutyric acid (GABA)ergic markers. Overall, our data confirm the depression-like phenotype of SERT−/− rats and highlight the ability of EE to restore behavioral and molecular alterations, thus promoting the opportunity to use EE as a supporting non-pharmacological approach to treat mood disorders. Full article
(This article belongs to the Special Issue Genes and Biomarkers of Mood and Anxiety Disorders)
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Review

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22 pages, 712 KiB  
Review
Genetic Biomarkers of Panic Disorder: A Systematic Review
by Artemii Tretiakov, Alena Malakhova, Elena Naumova, Olga Rudko and Eugene Klimov
Genes 2020, 11(11), 1310; https://doi.org/10.3390/genes11111310 - 04 Nov 2020
Cited by 5 | Viewed by 5067
Abstract
(1) Background: Although panic disorder (PD) is one of the most common anxiety disorders severely impacting quality of life, no effective genetic testing exists; known data on possible genetic biomarkers is often scattered and unsystematic which complicates further studies. (2) Methods: We used [...] Read more.
(1) Background: Although panic disorder (PD) is one of the most common anxiety disorders severely impacting quality of life, no effective genetic testing exists; known data on possible genetic biomarkers is often scattered and unsystematic which complicates further studies. (2) Methods: We used PathwayStudio 12.3 (Elsevier, The Netherlands) to acquire literature data for further manual review and analysis. 229 articles were extracted, 55 articles reporting associations, and 32 articles reporting no associations were finally selected. (3) Results: We provide exhaustive information on genetic biomarkers associated with PD known in the scientific literature. Data is presented in two tables. Genes COMT and SLC6A4 may be considered the most promising for PD diagnostic to date. (4) Conclusions: This review illustrates current progress in association studies of PD and may indicate possible molecular mechanisms of its pathogenesis. This is a possible basis for data analysis, novel experimental studies, or developing test systems and personalized treatment approaches. Full article
(This article belongs to the Special Issue Genes and Biomarkers of Mood and Anxiety Disorders)
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24 pages, 315 KiB  
Review
Blues in the Brain and Beyond: Molecular Bases of Major Depressive Disorder and Relative Pharmacological and Non-Pharmacological Treatments
by Elisabetta Maffioletti, Alessandra Minelli, Daniela Tardito and Massimo Gennarelli
Genes 2020, 11(9), 1089; https://doi.org/10.3390/genes11091089 - 18 Sep 2020
Cited by 16 | Viewed by 4601
Abstract
Despite the extensive research conducted in recent decades, the molecular mechanisms underlying major depressive disorder (MDD) and relative evidence-based treatments remain unclear. Various hypotheses have been successively proposed, involving different biological systems. This narrative review aims to critically illustrate the main pathogenic hypotheses [...] Read more.
Despite the extensive research conducted in recent decades, the molecular mechanisms underlying major depressive disorder (MDD) and relative evidence-based treatments remain unclear. Various hypotheses have been successively proposed, involving different biological systems. This narrative review aims to critically illustrate the main pathogenic hypotheses of MDD, ranging from the historical ones based on the monoaminergic and neurotrophic theories, through the subsequent neurodevelopmental, glutamatergic, GABAergic, inflammatory/immune and endocrine explanations, until the most recent evidence postulating a role for fatty acids and the gut microbiota. Moreover, the molecular effects of established both pharmacological and non-pharmacological approaches for MDD are also reviewed. Overall, the existing literature indicates that the molecular mechanisms described in the context of these different hypotheses, rather than representing alternative ones to each other, are likely to contribute together, often with reciprocal interactions, to the development of MDD and to the effectiveness of treatments, and points at the need for further research efforts in this field. Full article
(This article belongs to the Special Issue Genes and Biomarkers of Mood and Anxiety Disorders)
17 pages, 1438 KiB  
Review
RNA Editing and Modifications in Mood Disorders
by Alessandro Barbon and Chiara Magri
Genes 2020, 11(8), 872; https://doi.org/10.3390/genes11080872 - 31 Jul 2020
Cited by 16 | Viewed by 4223
Abstract
Major depressive disorder (MDD) is a major health problem with significant limitations in functioning and well-being. The World Health Organization (WHO) evaluates MDD as one of the most disabling disorders in the world and with very high social cost. Great attention has been [...] Read more.
Major depressive disorder (MDD) is a major health problem with significant limitations in functioning and well-being. The World Health Organization (WHO) evaluates MDD as one of the most disabling disorders in the world and with very high social cost. Great attention has been given to the study of the molecular mechanism underpinning MDD at the genetic, epigenetic and proteomic level. However, the importance of RNA modifications has attracted little attention until now in this field. RNA molecules are extensively and dynamically altered by a variety of mechanisms. Similar to “epigenomic” changes, which modify DNA structure or histones, RNA alterations are now termed “epitranscriptomic” changes and have been predicted to have profound consequences for gene expression and cellular functionality. Two of these modifications, adenosine to inosine (A-to-I) RNA editing and m6A methylations, have fascinated researchers over the last years, showing a new level of complexity in gene expression. In this review, we will summary the studies that focus on the role of RNA editing and m6A methylation in MDD, trying to underline their potential breakthroughs and pitfalls. Full article
(This article belongs to the Special Issue Genes and Biomarkers of Mood and Anxiety Disorders)
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32 pages, 1340 KiB  
Review
Orphan G Protein Coupled Receptors in Affective Disorders
by Lyndsay R. Watkins and Cesare Orlandi
Genes 2020, 11(6), 694; https://doi.org/10.3390/genes11060694 - 24 Jun 2020
Cited by 36 | Viewed by 9891
Abstract
G protein coupled receptors (GPCRs) are the main mediators of signal transduction in the central nervous system. Therefore, it is not surprising that many GPCRs have long been investigated for their role in the development of anxiety and mood disorders, as well as [...] Read more.
G protein coupled receptors (GPCRs) are the main mediators of signal transduction in the central nervous system. Therefore, it is not surprising that many GPCRs have long been investigated for their role in the development of anxiety and mood disorders, as well as in the mechanism of action of antidepressant therapies. Importantly, the endogenous ligands for a large group of GPCRs have not yet been identified and are therefore known as orphan GPCRs (oGPCRs). Nonetheless, growing evidence from animal studies, together with genome wide association studies (GWAS) and post-mortem transcriptomic analysis in patients, pointed at many oGPCRs as potential pharmacological targets. Among these discoveries, we summarize in this review how emotional behaviors are modulated by the following oGPCRs: ADGRB2 (BAI2), ADGRG1 (GPR56), GPR3, GPR26, GPR37, GPR50, GPR52, GPR61, GPR62, GPR88, GPR135, GPR158, and GPRC5B. Full article
(This article belongs to the Special Issue Genes and Biomarkers of Mood and Anxiety Disorders)
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