Anxiety Disorders Flashcards
Anxiety:
- Many different forms:
- Depend on…
- Occurs about twice as frequent in…
Important concepts
- Fear: the emotional response to…
- Anxiety: anticipation of…
- Panic: Abrupt surge of…
Anxiety has generally both a…
stimulus eliciting anxiety
females than males
real or perceived imminent threat
future threat
intense fear and/or discomfort
CNS and ANS component
Development of Anxiety Disorders (Age of Onset)
- Separation Anxiety
- Selective Mutism
- Specific Phobias
- Social Phobias
- Panic Disorder
- Agoraphobia
- GAD
- 3 to 12
- 2 to 5
- 7 to 11
- 8 to 15
- 20 to 24
- 17 to 25
- 18 to 35
Epidemiology of Anxiety Disorders
Lifetime Prevalence - ? % out of 100 develop AD
Female to Male Ratio
14 / 100
1 : 1
Twin studies have indicated clear heritability for most subgroups…%?
(roughly between 25 and 40%)
There is a common liability for anxiety which increases the risk for…
This common liability has a genetic component of…
and individual environmental component of…
and shared environmental component of…
phobias, GAD, panic disorders, PTSD
G 54%
Ei 40%
Es 6%.
Genes:
Neurotransmitter related genes
1. ?
2. ?
Neurodevelopment
- BDNF
- Tmem132
What type of genes are involved in major depression or anxiety disorders?
- Serotonin
- Dopamine
- Brain Derived Neurotrophic Factor
- involved in neuronal sprouting and connectivity
genes related to NT or genes related to neurodevelopment.
The neuroanatomy of fear and anxiety
Animal Research
In conflict paradigms, animals are confronted with two opposing drives one of which is fear (typically for open spaces). Thus in the open field and the elevated plus maze, animals are confronted with a novel environment that evokes both a drive to explore as well as a drive to be safe (i.e. close to a wall). The percentage of time spent out in the open is generally considered a measure of anxiety.
In conditioning paradigm, animals are exposed to a stimulus (such as a noise) which is paired with a small electric shock. Upon re-exposure to the stimulus, animals will show a fear response (which can be measures as an increase in freezing or a bodily change, such as an increase in heart rate).
Rats with the mutations called HOM, spend less time on the open arms than the alley 4
A genetic reduction in SERT leads to
anxious behaviour in rats
Amygdala plays a crucial role in…
Basolateral amygdala predominantly…
Central Amygdala promotes…
fear
dampens
fear
AD is associated with an…
There is a reduction in the inhibitory control from the..
Dysconnectivity disorder in which…
Deficits in GABA (inhibitory NT, interacts with ionotropic GABAA receptor)…
overactive amygdala
medial prefrontal (mPFC) and anterior cingulate
(ACC) cortex
the normal communication between brain regions is disturbed.
patients with AD have reduced levels of GABAA receptors in the brain
Genetic alterations in the SERT gene show signs of…
dysconnectivity and hyperreactivity of the amygdala when confronted with fearful or scary faces
mPFC activates the BLA, dampens the…
When the mPFC activity is lower, the BLA activity will be…
This leads to increased…
In part mediated by…
Serotonergic cells in the Dorsal R project to…
Reduction in serotonin transporter, mediates the…
Reduced capacity of mPFC, in part mediated via…
Normal people would have active control over fearful stimulus via…
AD patients do not, when a fearful stimulus occurs…
Under normal circumstances BLA controls inhibits the action of CeA. In patients with ADs the influence of mPFC on the BLA has…
As a result BLA activity is…
CeA and keeps it in check
lower, therefore, less control over the CeA
hyper-activity of the CeA, increased fearful response to stimuli – central to the neuroanatomy of ADs.
serotoninergic neurotransmission
all three key areas (mPFC and CeA and BLA)
dysconnectivity between the mPFC and BLA.
serotoninergic input into the mPFC, leads to a reduced activation of BLA, therefore, reduced control over the CeA.
mPFC and BLA
respond more intensely to the anxiety provoking response.
decreased
decreased, therefore the CeA is disinhibited.
Treatment of AD
- Antidepressants (takes time to work)
- TCA/MAOi/SSRI/SNRI
- Increase…
- Reduce amygdala…
- Inhibits the hyperactivity…
- Restores the balance between…
5-HT and/or NE neurotransmission
hyperreactivity
in the CeA, by increasing the control of the BLA over the CeA.
PFC and BLA, helps to the control the hyperactivity.
Treatment of AD
- Benzodiazepines (works faster)
- diazepam, clonazepam and oxazepam
- Increase…
- More…
- Act as…
- dampen CNS in the…
GABA receptors is a ion channel, allows Cl- ions to flow into the cell. Inside of cell -80mV, voltage-gated Na ion channels open at -60mV, make inside of cell more negative, it’s more difficult for the cells to become activated.
By stimulating GABA receptors dampens the neuronal activity.
GABAA receptor is an ionotropic receptor composed of... Total of... Leading to a... GABA binds to... Benzodiazepines bind to... Different α subunits have different... α1: ? α2 and α3: ? α2 and γ: ?
GABA activity side effects positive allosteric modulators of the GABAA receptor. amygdala and hypothalamus activity
five peptides
19 different subunits
large variety of GABAA receptors
the interface between alpha and beta subunits
the interface between alpha and gamma subunits
localization in the brain and play different roles
sedation and amnesia
vigilance
fear, anxiety (highly localized in amygdala/hypothalamus/ basal ganglia and hippocampus)
Treatment of AD
- Beta-Blockers
- propranolol, atenolol
- inhibit the peripheral consequences (e.g., increased heart rate/sweating and blood pressure) of fear and anxiety by acting on the…
sympathetic autonomic nervous system
ANS consists of…
Behave like…
- SNS
- Most active during…
- Flight or fight reaction
- Activating - PNS
- Most active during…
- Recuperation/regeneration
Sympathetic nervous system and Parasympathetic nervous system
Functional antagonists
active situations (day) rest (night)
