Genetic dysfunction of serotonin 2A receptor hampers response to antidepressant drugs: A translational approach

@article{Qesseveur2016GeneticDO,
  title={Genetic dysfunction of serotonin 2A receptor hampers response to antidepressant drugs: A translational approach},
  author={Ga{\"e}l Qesseveur and Anne-C{\'e}cile Petit and Hai Thanh Nguyen and Lionel Dahan and Romain Colle and Samuel Rotenberg and Isabelle Seif and Pauline Robert and Denis J. David and Jean-Philippe Guilloux and Alain M. Gardier and C{\'e}line Verstuyft and Laurent Becquemont and Emmanuelle Corruble and Bruno P. Guiard},
  journal={Neuropharmacology},
  year={2016},
  volume={105},
  pages={142-153}
}
Pharmacological studies have yielded valuable insights into the role of the serotonin 2A (5-HT2A) receptor in major depressive disorder (MDD) and antidepressant drugs (ADs) response. However, it is still unknown whether genetic variants in the HTR2A gene affect the therapeutic outcome of ADs and the mechanism underlying the regulation of such response remains poorly described. In this context, a translational human-mouse study offers a unique opportunity to address the possibility that… Expand
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TLDR
This current investigation supported the link between HTR2A variants and antidepressant therapeutic response in MDD but not with MDD susceptibility, and identified 14 polymorphisms as suggestive markers for therapeutic responded in both meta- and mega-analyses. Expand
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The results indicate that while there is significant potential for predicting treatment response associated with two 5-HT related genes: SLC6A4 and HTR2A, there is much work left to be done to establish conclusive evidence for and feasibility of pharmacogenetic testing. Expand
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This chapter aims to summarize the up-to-day evidence-based biomedical knowledge on serotonin-2A (5-HT2A) receptors and their role in pathophysiology and treatment of central nervous system (CNS)… Expand
Highlights on Pharmacogenetics and Pharmacogenomics in Depression
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This chapter summarizes the current knowledge about the pharmacogenetics and pharmacogenomics of antidepressant drugs in major depressive disorder and analysis approaches derived from GWAS are expected to provide better power to identify the complex polygenic profile modulating antidepressant response. Expand
The association of β-arrestin2 polymorphisms with response to antidepressant treatment in depressed patients
TLDR
It is shown that GG/GT patients for rs4522461 and AA/AC patients forrs4790694 have a lower response to AD than other genotype groups, providing additional evidence that ARRB2 is a regulator of intracellular signal transduction processes involved in AD treatment. Expand
Pharmacogenetics and Imaging–Pharmacogenetics of Antidepressant Response: Towards Translational Strategies
TLDR
There is mounting evidence that genetic factors exert their impact on treatment response by influencing brain structural and functional changes during antidepressant treatment, and combining neuroimaging and genetic methods may be a more powerful way to detect biological mechanisms of response than either method alone. Expand
Genetic variants in major depressive disorder: From pathophysiology to therapy
TLDR
The inconsistency between most genetic studies in depression suggests a significant role of environmental stress and the optimization of current medications can be approached by pharmacogenomics, where metabolizing enzyme polymorphisms remain prominent determinants of therapeutic success. Expand
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TLDR
This study investigated the role of a set of genes involved in different pathways in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment to support the involvement of some candidate genes in the outcomes of treatments for mood disorders, as well as in BD risk and other disease features. Expand
Revisiting the behavioral genetics of serotonin: relevance to anxiety and depression
TLDR
The behavioral consequences of manipulation of genes that regulate serotonergic signaling in rodents are described and analogous genetic association studies in humans that relate to psychiatric disorders are reviewed, with a focus on depression and anxiety disorders. Expand
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