Social Anxiety Disorder
Social Anxiety Disorder:
Social anxiety disorder is a mental condition where the individual
experiences extreme levels of fear and anxiety arising in relation to social and
public situations, potentially impairing normal functionality in their daily life. The
origins of the anxiety disorder are caused by multiple factors, affiliated in
combination with others, like in the case of genetic and environmental factors.
Through the use of neuroimaging studies, researches have been able to examine
patients with SAD stimulating the brain through anticipation of speech or faces
during functional magnetic resonance imaging. The studies expressed activity in
both limbic and prefrontal regions particularly hyperactivity in the amygdala
region, which alludes to the fact that patients with social phobia have altered
neurological pathways when processing fear response. [1]These findings further
suggest that SAD patients are more susceptible to a disruption of the serotonergic
system, where they may be a carrier of a short allele polymorphism in the serotonin
transporter compared to the homozygous long allele found in healthy patients.
[2]Studies have been conducted with the serotonin transporter knockout and wild
type, assessing social interaction among mice. Currently a functional
pharmacotherapy being applied, are the SSRI’s: paroxetine, sertraline,
fluvoxamine, fluoxetine, and escittalopram in randomized clinical trials examining
dosages and efficacy within adult patients who attribute to SAD symptoms, as well
challenges in regards to pharmacotherapy. [3]
Video:
http://www.youtube.com/watch?v=qRRemYuSwII&feature=results_main&playne
xt=1&list=PL2DA9DBB9713868F4
Social Anxiety Disorder Causes
Environmental causes
The familial context poses as a potential risk factor in developing SAD. Familial
transmission of SAD can arise on one hand due to the parent’s ability to facilitate
children’s social interaction with others and on the other hand, the degree of
parental control over them. This establishes a major link between parental rearing
and potential risk of offspring anxiety arising. (put in reference) In terms of
parental rearing, this can include rejection, overprotection, as well as lack of
emotional warmth from the parent towards the child. [4]Along with this, it has
been reported that offspring are highly susceptible to social anxiety disorder in
the case where there is an established history of mental disorders in the family. A
study was conducted examining this relationship using “Yale Family Study” and
concluded a “linear increase in risk for anxiety in general and social anxiety
disorder in particular when the number of affected parents was considered.”[5]
Through twin studies and animal models the etiology of SAD has been shown to
be predominated by environmental factors in comparison to genetic inheritance.
(http://journals2.scholarsportal.info.myaccess.library.utoronto.ca/tmp/13437639
912437800765.pd)
1.1.3 Genetics and heredity
Discovering the genetics of social anxiety disorder, through the first genome-wide
linkage scan ever performed, which showed the expression of chromosome 16
risk locus.[6]In turn, this lead to detection of the candidate gene d SLC6A2 in
this area, also considered to be the norepinephrine transporter
protein locus. [7]This transporter controls the re-uptake of both
norepinephrine and dopamine neurotransmitters, relating to the
idea that abnormal dopaminergic systems are plausible cause in
relation to social phobia. [8]The major neurological pathway under study is
the serotonergic system, where patients may be a carrier of a short allele
polymorphism in the serotonin transporter compared to the homozygous long allele
found in healthy patients, proved to be underlying factor to increasing
susceptibility. [9]
1.1 Brain regions
1.2.1 Hyperactivity in the amygdala region
In recent times, there have been neuroimaging studies conducted on SAD
patients implicating hyperactivity in the amygdala region of the brain, in reaction
to social threat. [10]The amygdala being a central regulator in processing and the
expression of an individual’s emotions, fittingly associates with this mental
disorder, where there is a tendency to fear social situations, even more so
disapproval by others. [11]Studies performed in obtaining these results commonly
are, PET, SPECT and FMRI scans most often comparing healthy patient’s brain
activity in relation to people diagnosed with social phobia, expressing “differential
activation in the limbic–prefrontal circuit.” [12]
1.2.2 Comparison of excitability of the amygdala region in response to facial expression
in patients with social anxiety disorder versus healthy individuals
To further examine the hyper-activated amygdala in patients with social anxiety
disorder, some scientists narrowed their experiments, specifically analyzing the
response to emotional expressions: happy, angry and neutral faces. Generally,
these experiments are performed using social phobic against healthy subjects
presenting them with facial photographic stimuli, while measuring the response
through functional magnetic resonance imaging techniques. [13]The results
expressed greater activity in the right amygdala region corresponding to angry
faces, in comparison to happy and neutral expressions in social phobic patients.
This is demonstrative of the association of not only the responsiveness of
amygdala to aversive faces, but the severity of the symptoms the patient may be
enduring. [14]Along with this, harsh displays of expressions act as an ideal stimuli,
in that they are correspondent to a threatening social signal even a threat that
will target the stimulation of the amygdala, and even more so in social phobic
individuals. ( Heide Klumpo, 2010)
1.2 Serotonergic pathway
1.2.1 short variation of 5’HTT promoter allele
The serotonergic pathway in social anxiety patients been noted to contain a
polymorphism located in the promoter region of the human serotonin transporter
(5’HTT) gene. In healthy humans, normally contain the long allele of this gene, as
for those with anxiety-related traits they instead, contain the short version 5HTTLPR. [15]Individuals containing one or two short alleles can
lead to the disruption in the serotonergic pathway, as a result,
decreasing the serotonin reuptake in the synapse by the (5’HTT)
transporter. [16]The effect on the synapse, causes a reduction in the
transcription efficiency of the 5-HTT promoter, decreasing both the tranporters
expression and reuptake from the synaptic cleft into the cell. [17]This short
allele in turn, poses as a risk factor in developing anxiety and
other related psychiatric disorders. [18]Also, in terms of the
neuronal activity in the amygdala, it was shown to increase when
the individual had a short allele, unlike when holding the
homozygous long allele.[19]In respect to symptoms, these
patients with the variant have been characterized by higher
neuroticism, anxiety and depression than the patients lacking this
short allele did not express any related anxiety- traits or
symptoms.[20]
1.3 Animal model
1.3.1 5’HTT promoter allele assessing social interaction
Animal models are effectively employed to further asses’ genetics and to learn
the origin of arising anxiety-related behaviours, as well the associated
psychiatric disorders. In social anxiety disorder, the underlying genetic cause
is a disruption in the 5’HTT gene, which can be translated into a genetic
mouse model. To accomplish this, a homozygous knockout mouse is designed
by inactivating completely the function of the 5’HTT gene found in humans,
through a 5-HTTLPR-like sequence in mice. [21]Also for the experiment,
taking into consideration modifying a mouse into a heterozygote, pertaining
less 5’HTT activity than the knockout mouse and lastly a wild-type mouse,
which serves as the healthy control, with normal levels of 5’HTT.
[22]Specifically, in testing the behaviours in respect to social phobia, all three
mouse variants must be assessed in facing social situations, certain
behaviours and other encounters, further helping to examine the effects of the
disruption in the serotonergic system. Across studies, the SERT-/- mouse
model behavior presented itself with negative behavioral outcomes including,
higher anxiety and decreased social behavior. [23]In assessing the behavior of
the mice using various test, such as “nest building, grooming, sticky label, novel
object, ethogram, social interaction, tics, wire hanging, balancing, rope climbing,
food finding, locomotion and chewing pattern tests”, helped prove and support
this theory. [24]Particularly shown in the social interaction test, where the
differences between the SERT -/- and SERT +/+ were highly distinguishable in that
the knockout mouse model had minimal exploration activity, and neither a great
deal of hypoactivity, leading to confirm the disabiling effect of anxiety caused by
the disruption in the serotonin pathway.
1.2 Treatments
1.2.1 SSRI’s
Social Anxiety Disorder first-line of pharmacotherapy comes in the form of SSRI
treatment. However, when dealing with mental disorder, diagnosis of the illness is
rather difficult in comparison to other diseases, since they are comorbid and
symptoms can greatly range. Therefore, additional steps are taken during the
process of prescribing these medications, known as an “algorithmic system”. This
system is intended as a guideline for clinicians to ensure the most efficient
treatment for patients, as well as indicating areas that still need attention and
further research. It is designed by eight-sequential steps, beginning with the
diagnosis, then treatment and monitoring the treatment effects in long-term.
[25]Each step addresses major aspects of prescribing medication, while assisting
the clinician in decision-making for the optimal treatment for the patient. [26]SSRI
is most commonly prescribed medication, based on its consistent efficacy, safety
in regards to the patients, tolerability and efficiency in treatment and good
outcomes. [27]Currently, there are several types of functional SSRI’s, but out of
the few there are only two that have been validated as FDA- approved for clinical
use and treatment of SAD, and they are paroxetine, and sertraline. [28]The
duration of the treatment should be maintained from 3-6 months after the patient
has responded. [29]These periods can vary upon individual cases, and depending if
pharmacotherapy is joined with psychotherapy.
1.2.2 Challenges of Treatments
In treating patients with social anxiety disorder, various challenges and limitations
continue to arise. Evidently the issue of terminating treatment after a 12-20 week
period or even after 5 months, the patient is at risk of relapse. [30]Studies have
suggested that this may be due to the limited period patients are committing in
taking the medication, on the other hand it being necessary to combine
pharmacotherapy with an additional treatment, such as psychotherapy. Not only
is there a chance of relapse, but the onset of the therapeutic effects of the drug
may take up to 2-4 weeks to be noticed and help in decreasing anxious-type of
behaviour. [31]In social anxiety the detection of comorbidity, poses as another
factor for treatment resistance to the pharmacotherapy applied. Essentially, there
is a lack of a thorough understanding of comorbidity and comorbidity’s influence
on particular treatments. [32]
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[22] Lars
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