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Towards the Molecular Foundations of Glutamatergic-targeted Antidepressants

Kroes, Roger A and Nilsson, Carol L. LU (2017) In Current neuropharmacology 15(1). p.35-46
Abstract

BACKGROUND: Depression affects over 120 million individuals of all ages and is the leading cause of disability worldwide. The lack of objective diagnostic criteria, together with the heterogeneity of the depressive disorder itself, makes it challenging to develop effective therapies. The accumulation of preclinical data over the past 20 years derived from a multitude of models using many divergent approaches, has fueled the resurgence of interest in targeting glutamatergic neurotransmission for the treatment of major depression.

OBJECTIVE: The emergence of mechanistic studies are advancing our understanding of the molecular underpinnings of depression. While clearly far from complete and conclusive, they offer the potential to... (More)

BACKGROUND: Depression affects over 120 million individuals of all ages and is the leading cause of disability worldwide. The lack of objective diagnostic criteria, together with the heterogeneity of the depressive disorder itself, makes it challenging to develop effective therapies. The accumulation of preclinical data over the past 20 years derived from a multitude of models using many divergent approaches, has fueled the resurgence of interest in targeting glutamatergic neurotransmission for the treatment of major depression.

OBJECTIVE: The emergence of mechanistic studies are advancing our understanding of the molecular underpinnings of depression. While clearly far from complete and conclusive, they offer the potential to lead to the rational design of more specific therapeutic strategies and the development of safer and more effective rapid acting, long lasting antidepressants.

METHODS: The development of comprehensive omics-based approaches to the dysregulation of synaptic transmission and plasticity that underlies the core pathophysiology of MDD are reviewed to illustrate the fundamental elements.

RESULTS: This review frames the rationale for the conceptualization of depression as a "pathway disease". As such, it culminates in the call for the development of novel state-of-the-art "-omics approaches" and neurosystems biological techniques necessary to advance our understanding of spatiotemporal interactions associated with targeting glutamatergic-triggered signaling in the CNS.

CONCLUSION: These technologies will enable the development of novel psychiatric medications specifically targeted to impact specific, critical intracellular networks in a more focused manner and have the potential to offer new dimensions in the area of translational neuropsychiatry.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Antidepressive Agents, Depressive Disorder, Major, Gene Expression Regulation, Humans, Neuronal Plasticity, Receptors, N-Methyl-D-Aspartate, Journal Article, Review
in
Current neuropharmacology
volume
15
issue
1
pages
12 pages
external identifiers
  • scopus:85011741697
ISSN
1570-159X
DOI
10.2174/1570159X14666160309114740
language
English
LU publication?
no
id
2ef7da5c-5c4f-4600-9a36-b622929733bb
date added to LUP
2017-05-16 10:17:15
date last changed
2017-05-21 05:01:33
@article{2ef7da5c-5c4f-4600-9a36-b622929733bb,
  abstract     = {<p>BACKGROUND: Depression affects over 120 million individuals of all ages and is the leading cause of disability worldwide. The lack of objective diagnostic criteria, together with the heterogeneity of the depressive disorder itself, makes it challenging to develop effective therapies. The accumulation of preclinical data over the past 20 years derived from a multitude of models using many divergent approaches, has fueled the resurgence of interest in targeting glutamatergic neurotransmission for the treatment of major depression.</p><p>OBJECTIVE: The emergence of mechanistic studies are advancing our understanding of the molecular underpinnings of depression. While clearly far from complete and conclusive, they offer the potential to lead to the rational design of more specific therapeutic strategies and the development of safer and more effective rapid acting, long lasting antidepressants.</p><p>METHODS: The development of comprehensive omics-based approaches to the dysregulation of synaptic transmission and plasticity that underlies the core pathophysiology of MDD are reviewed to illustrate the fundamental elements.</p><p>RESULTS: This review frames the rationale for the conceptualization of depression as a "pathway disease". As such, it culminates in the call for the development of novel state-of-the-art "-omics approaches" and neurosystems biological techniques necessary to advance our understanding of spatiotemporal interactions associated with targeting glutamatergic-triggered signaling in the CNS.</p><p>CONCLUSION: These technologies will enable the development of novel psychiatric medications specifically targeted to impact specific, critical intracellular networks in a more focused manner and have the potential to offer new dimensions in the area of translational neuropsychiatry.</p>},
  author       = {Kroes, Roger A and Nilsson, Carol L.},
  issn         = {1570-159X},
  keyword      = {Animals,Antidepressive Agents,Depressive Disorder, Major,Gene Expression Regulation,Humans,Neuronal Plasticity,Receptors, N-Methyl-D-Aspartate,Journal Article,Review},
  language     = {eng},
  number       = {1},
  pages        = {35--46},
  series       = {Current neuropharmacology},
  title        = {Towards the Molecular Foundations of Glutamatergic-targeted Antidepressants},
  url          = {http://dx.doi.org/10.2174/1570159X14666160309114740},
  volume       = {15},
  year         = {2017},
}