5-HT(1A) Receptor Function in Major Depressive Disorder
Dysfunction of the serotonin 1A receptor (5-HT(1A)) may play a role in the genesis of major depressive disorder (MDD). Here we review the pharmacological, post-mortem, positron-emission tomography (PET), and genetic evidence in support of this statement. We also touch briefly on two MDD-associated p...
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2009
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| Online-ссылка: | https://ncbi.nlm.nih.gov/pmc/articles/PMC2736801/ https://ncbi.nlm.nih.gov/pubmed/19428959 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1016/j.pneurobio.2009.01.009 |
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pubmed-27368012010-05-01 5-HT(1A) Receptor Function in Major Depressive Disorder Savitz, Jonathan Lucki, Irwin Drevets, Wayne C Prog Neurobiol Article Dysfunction of the serotonin 1A receptor (5-HT(1A)) may play a role in the genesis of major depressive disorder (MDD). Here we review the pharmacological, post-mortem, positron-emission tomography (PET), and genetic evidence in support of this statement. We also touch briefly on two MDD-associated phenotypes, cognitive impairment and somatic pain. The results of pharmacological challenge studies with 5-HT(1A) receptor agonists are indicative of blunted endocrine responses in depressed patients. Lithium, valproate, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and other treatment, such as electroconvulsive shock therapy (ECT), all increase post-synaptic 5-HT(1A) receptor signaling through either direct or indirect effects. Reduced somatodendritic and postsynaptic 5-HT(1A) receptor numbers or affinity have been reported in some post-mortem studies of suicide victims, a result consistent with well-replicated PET analyses demonstrating reduced 5-HT(1A) receptor binding potential in diverse regions such as the dorsal raphe, medial prefrontal cortex (mPFC), amygdala and hippocampus. 5-HT(1A) receptor knockout (KO) mice display increased anxiety-related behavior, which, unlike in their wild-type counterparts, cannot be rescued with AD treatment. In humans, the G allele of a single nucleotide polymorphism (SNP) in the 5-HT(1A) receptor gene (HTR1A; rs6295), which abrogates a transcription factor binding site for Deaf-1 and Hes5, has been reported to be over-represented in MDD cases. Conversely, the C allele has been associated with better response to AD drugs. We raise the possibility that 5-HT(1A) receptor dysfunction represents one potential mechanism underpinning MDD and other stress-related disorders. 2009-02-07 2009-05 /pmc/articles/PMC2736801/ /pubmed/19428959 http://dx.doi.org/10.1016/j.pneurobio.2009.01.009 Text en |
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Inglês |
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Article Savitz, Jonathan Lucki, Irwin Drevets, Wayne C 5-HT(1A) Receptor Function in Major Depressive Disorder |
| description |
Dysfunction of the serotonin 1A receptor (5-HT(1A)) may play a role in the genesis of major depressive disorder (MDD). Here we review the pharmacological, post-mortem, positron-emission tomography (PET), and genetic evidence in support of this statement. We also touch briefly on two MDD-associated phenotypes, cognitive impairment and somatic pain. The results of pharmacological challenge studies with 5-HT(1A) receptor agonists are indicative of blunted endocrine responses in depressed patients. Lithium, valproate, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and other treatment, such as electroconvulsive shock therapy (ECT), all increase post-synaptic 5-HT(1A) receptor signaling through either direct or indirect effects. Reduced somatodendritic and postsynaptic 5-HT(1A) receptor numbers or affinity have been reported in some post-mortem studies of suicide victims, a result consistent with well-replicated PET analyses demonstrating reduced 5-HT(1A) receptor binding potential in diverse regions such as the dorsal raphe, medial prefrontal cortex (mPFC), amygdala and hippocampus. 5-HT(1A) receptor knockout (KO) mice display increased anxiety-related behavior, which, unlike in their wild-type counterparts, cannot be rescued with AD treatment. In humans, the G allele of a single nucleotide polymorphism (SNP) in the 5-HT(1A) receptor gene (HTR1A; rs6295), which abrogates a transcription factor binding site for Deaf-1 and Hes5, has been reported to be over-represented in MDD cases. Conversely, the C allele has been associated with better response to AD drugs. We raise the possibility that 5-HT(1A) receptor dysfunction represents one potential mechanism underpinning MDD and other stress-related disorders. |
| author |
Savitz, Jonathan Lucki, Irwin Drevets, Wayne C |
| author_facet |
Savitz, Jonathan Lucki, Irwin Drevets, Wayne C |
| author_sort |
Savitz, Jonathan |
| title |
5-HT(1A) Receptor Function in Major Depressive Disorder |
| title_short |
5-HT(1A) Receptor Function in Major Depressive Disorder |
| title_full |
5-HT(1A) Receptor Function in Major Depressive Disorder |
| title_fullStr |
5-HT(1A) Receptor Function in Major Depressive Disorder |
| title_full_unstemmed |
5-HT(1A) Receptor Function in Major Depressive Disorder |
| title_sort |
5-ht(1a) receptor function in major depressive disorder |
| publishDate |
2009 |
| url |
https://ncbi.nlm.nih.gov/pmc/articles/PMC2736801/ https://ncbi.nlm.nih.gov/pubmed/19428959 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1016/j.pneurobio.2009.01.009 |
| _version_ |
1752208210584928256 |