Research Topic

Role of the Serotonergic System in Pathology of Major Depressive Disorders

About this Research Topic

Serotonin is involved in many physiological or pathophysiological processes including modulating mood and cognition. Seven distinct receptors (5-HT1-7), each with several subtypes, have been identified for serotonin. These receptors are different in terms of localization and downstream signaling. Serotonin has been always the focus of attention as a drug discovery target in different psychiatric disorders, particularly major depressive disorder (MDD). Because of the development of selective agonists and antagonists for serotonin receptors as well as transgenic animal models of cognitive disorders, our understanding of the role of serotonergic transmission in the pathology of MMD has improved in recent years. A large body of evidence indicates the interplay between serotonergic transmission and other neurotransmitters including acetylcholine, dopamine, GABA, and glutamate, in the neurobiological control of different behaviors and memory. In addition, both human and experimental studies have shown an alteration in the density of serotonergic receptors and their function in mood disorders.

The role of serotonin in MDD is the focus of many experimental and human studies. The results of different studies reflect the complexity of serotonin signaling and bioavailability through many receptors and transporters in different brain regions. The role of serotonin transporters has been established in MDD, while the majority of the known receptors for serotonin have been implicated in depression or depressive-like behavior. Human brain imaging and genetic studies point to the involvement of 5-HT1A, 5-HT1B, 5-HT2, and 5-HT3 receptors in MDD. In rodents, the availability of tissue-specific and inducible knockout mouse lines make it possible to identify the involvement of different serotonin receptors and transporters in a cell-type specific manner. However, our knowledge is still not deep enough on the role of different serotonin receptors and their downstream targets in the regulation of mood and behavior New studies on serotonin receptor signaling and the role of serotonin transporters in neuroglia interaction can make big progress in the field of neuropsychopharmacology.

This Research Topic aims to collect Original Research articles, Review articles, and Opinion pieces on:

• Role of different serotonin receptors (particularly 5-HT1, 5-HT2, 5-HT3, 5-HT4 and 5-HT7) and transporters (SERT and VMATs) in experimental models of depression including different stress models;
• Post-mortem studies investigating the role of the serotonergic system in pathology of MDD
• Role of the serotonergic system in neurogenesis in association with MDD
• Imaging studies addressing the importance of the serotonergic system in MDD pathology
• Role of the serotonergic system in neuroinflammation and a possible link with MDD
• Cell-specific and electrophysiological studies to investigate the role of the serotonergic system in MDD


Keywords: Major Depressive Disorder, MDD, Serotonin, 5-HT receptor, SERT, VMAT


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Serotonin is involved in many physiological or pathophysiological processes including modulating mood and cognition. Seven distinct receptors (5-HT1-7), each with several subtypes, have been identified for serotonin. These receptors are different in terms of localization and downstream signaling. Serotonin has been always the focus of attention as a drug discovery target in different psychiatric disorders, particularly major depressive disorder (MDD). Because of the development of selective agonists and antagonists for serotonin receptors as well as transgenic animal models of cognitive disorders, our understanding of the role of serotonergic transmission in the pathology of MMD has improved in recent years. A large body of evidence indicates the interplay between serotonergic transmission and other neurotransmitters including acetylcholine, dopamine, GABA, and glutamate, in the neurobiological control of different behaviors and memory. In addition, both human and experimental studies have shown an alteration in the density of serotonergic receptors and their function in mood disorders.

The role of serotonin in MDD is the focus of many experimental and human studies. The results of different studies reflect the complexity of serotonin signaling and bioavailability through many receptors and transporters in different brain regions. The role of serotonin transporters has been established in MDD, while the majority of the known receptors for serotonin have been implicated in depression or depressive-like behavior. Human brain imaging and genetic studies point to the involvement of 5-HT1A, 5-HT1B, 5-HT2, and 5-HT3 receptors in MDD. In rodents, the availability of tissue-specific and inducible knockout mouse lines make it possible to identify the involvement of different serotonin receptors and transporters in a cell-type specific manner. However, our knowledge is still not deep enough on the role of different serotonin receptors and their downstream targets in the regulation of mood and behavior New studies on serotonin receptor signaling and the role of serotonin transporters in neuroglia interaction can make big progress in the field of neuropsychopharmacology.

This Research Topic aims to collect Original Research articles, Review articles, and Opinion pieces on:

• Role of different serotonin receptors (particularly 5-HT1, 5-HT2, 5-HT3, 5-HT4 and 5-HT7) and transporters (SERT and VMATs) in experimental models of depression including different stress models;
• Post-mortem studies investigating the role of the serotonergic system in pathology of MDD
• Role of the serotonergic system in neurogenesis in association with MDD
• Imaging studies addressing the importance of the serotonergic system in MDD pathology
• Role of the serotonergic system in neuroinflammation and a possible link with MDD
• Cell-specific and electrophysiological studies to investigate the role of the serotonergic system in MDD


Keywords: Major Depressive Disorder, MDD, Serotonin, 5-HT receptor, SERT, VMAT


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

05 February 2021 Abstract
05 June 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

05 February 2021 Abstract
05 June 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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