Editor's
comment:
Quite by chance, two authoratitive reviews have just
appeared in two different journals featuring 5-HT1A
receptor dysfunction and implicating it in depressive
disorders and anxiety disorders
respectively. Reading these two reviews it becomes
clear why comorbid anxiety and depression is the rule
rather than the exception with rates of comorbidity of 60
- 70%.
Selected review
N° 63
5-HT(1A)
receptor function in major depressive
disorder.
Savitz J, Lucki
I, Drevets WC. Mood and
Anxiety Disorders Program, NIH/NIMH, Bethesda,
USA
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 antidepressant drug (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 deformed
epidermal autoregulatory factor-1 (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.
Reference:
Savitz J, Lucki I, Drevets WC. (2009) 5-HT(1A)
receptor function in major depressive disorder.
Prog Neurobiol. 88:17-31. Full
text available
(Subscription
required)
Author's e-mail:savitzj@mail.nih.gov
Added
June 2009
Selected review
N° 64
The
Serotonin-1A Receptor in Anxiety
Disorders.
Akimova E,
Lanzenberger R, Kasper S. Department
of Psychiatry and Psychotherapy, Medical University
of Vienna, Austria.
The serotonin
system plays an important role in the neural
processing of anxiety. The involvement of the main
inhibitory serotonergic receptor, the serotonin-1A
(5-HT1A) subtype, in dysfunctional forms of anxiety
has been supported by findings from a wide range of
preclinical research and clinical trials, including
treatment studies, genetic research, and
neuroimaging data. The following article summarizes
preclinical results with a focus on 5-HT1A receptor
knockout and transgenic mice as genetic models of
anxiety. Behavioral, autonomic, and
endocrinological changes in these mice are
reported. This article also presents genetic
polymorphisms in humans associated with increased
anxiety scores and pharmacological data focused on
5-HT1A receptor agonists and antagonists.
Furthermore, molecular neuroimaging results are
presented. Recent positron emission tomography
(PET) studies have reported reduced 5-HT1A receptor
binding in patients with panic disorder and social
anxiety disorder, but not in posttraumatic stress
disorder. In healthy subjects, increased anxiety
scores might be associated with lower 5-HT1A
receptor binding. This overview of preclinical and
clinical data provides strong evidence for the key
role of the 5-HT1A receptor in the serotonergic
dysregulation of anxiety disorders.
Reference:
Akimova E, Lanzenberger R, Kasper S. (2009) The
Serotonin-1A Receptor in Anxiety Disorders. Biol
Psychiatry. in press Full
text available
(Subscription
required)
Author's e-mail:sci-biolpsy@meduniwien.ac.at
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