Anxiety disorders: Neurobiology, neurochemistry and treatment Flashcards
The amygdala is a part of the brain that derives its name from the greek word for almond. It is composed of lots of connected nuclei, that then go on to connect to lots of parts of the brain. What is its primary function in the brain?
1 - movements
2 - hearing
3 - sight
4 - emotional processing
4 - emotional processing
- also part of the limbic system (emotion and memory)
The amygdala is a part of the brain that derives its name from the greek word for almond. It is composed of lots of nuclei connected, that then go on to connect to lots of parts of the brain. Its primary function in the brain is emotion, however, what is potentially the strongest emotion that it seems to be strongly associated with?
1 - happiness
2 - sadness
3 - fear
4 - anxiety
3 - fear
- surgery to remove the amygdala oddly removes fear
The amygdala is a part of the brain that derives its name from the greek word for almond. It is composed of lots of connected nuclei, that then go on to connect to lots of parts of the brain. Its primary function in the brain is emotion, with fear being a key emotion it processes. Label the 4 key parts of the brain that feed sensory information into the amygdala using the labels below:
- anterior cingulate gyrus
- thalamus
- somatosensory cortex
- hippocampus (relates fearful memories to current context)
1 - somatosensory cortex
2 - anterior cingulate gyrus
3 - thalamus
4 - hippocampus (relates fearful memories to current context)
When we are scared, the sensation of fear is sent to the amygdala. Once here it excites the lateral hypothalamus, causing an autonomic response. What is this response?
- excited the sympathetic nervous system
- initiating the acute stress response (bodies response to fear)
- fight or flight response (hypothalamus is driver in brain)
When we are scared, the sensation of fear is sent to the amygdala, which then transmits the signal to the hypothalamus. The hypothalamus then transmits the signal to the locus coeruleus causing a behavioural response, which is fight of flight. Which group of nuclei is stimulated in the brain to initiate this behavioural response?
1 - nucleus accumbens
2 - ventral tegmental
3 - locus coeruleus
4 - raphe nuclei
3 - locus coeruleus
- principal site for brain synthesis of norepinephrine
What is the locus coeruleus, which is latin for blue spot?
1 - primary site in brain for synthesis of norepinephrine
2 - primary site in adrenal gland for the synthesis of norepinephrine
3 - primary site in brain for synthesis of serotonin
4 - primary site in brain for synthesis of dopamine
1 - primary site in brain for synthesis of norepinephrine
- located in the rostral pons of the brainstem
- part of the reticular activating system (important in descending pathways)
When we are scared, the sensation of fear is sent to the amygdala. Once here it excites the periventricular hypothalamus, and HPA axis activation causing an endocrine response. What is this response?
- HPA axis is important in out stress response
- initiating the acute stress response (bodies response to fear)
- release of cortisol from the adrenal cortex as a glucocorticoid
The amygdala signals different parts of the brain when we are scared. What are the 3 functions that make up the acute stress response?
1 - autonomic, behavioural, endocrine
2 - emotional, behavioural, endocrine
3 - autonomic, emotional, endocrine
4 - autonomic, behavioural, emotional
1 - autonomic, behavioural, endocrine
- autonomic (fight of flight)
- behavioural (fear)
- endocrine (cortisol response)
What is the flow of the HPA axis, which is part of the acute stress response?
- amygdala activates hypothalamus
- hypothalamus releases corticotrophin releasing hormone (CRH), which acts on the pituitary
- pituitary releases adrenocorticotropic hormone (ACTH) which acts on adrenal glands
- adrenal cortex releases cortisol (CORT: stress hormone, glucocorticoid)
The HPA axis (hypothalamus, pituitary, adrenal gland) has a negative feedback look, what is this?
- cortisol released from adrenal cortex
- signals hypothalamus, pituitary and hippocampus
- too much cortisol generally turns off the HPA axis
The HPA axis (hypothalamus, pituitary, adrenal gland) has a negative feedback look, where cortisol released from adrenal cortex signals the hypothalamus, hippocampus and pituitary gland. How is the hypothalamus regulated by cortisol?
- hippocampus and hypothalamus contain glucocorticoid receptors
- cortisol is a glucocorticoid so it binds to receptors
- hippocampus provides inhibitory action on hypothalamus and inhibits release of corticotrophin releasing hormone
Dysregulation of the he tHPA axis (hypothalamus, pituitary, adrenal gland) will affect the levels of cortisol, where it may be chronically continually stimulated. What disorders has this been associated with?
1 - anxiety, stress, mood related disorders
2 - depression, stress, mood related disorders
3 - anxiety, delirium, mood related disorders
4 - anxiety, stress, generalised anxiety disorder
1 - anxiety, stress, mood related disorders
When we are scared, the sensation of fear is sent to the amygdala. Once here it excited the locus coeruleus causing a behavioural response. The locus coeruleus is the principal site for brain synthesis of norepinephrine, which can initiate a behaviour of the acute stress response (bodies response to fear). What are the 2 behaviours if can trigger?
- fight or flight
Noradrenaline is released throughout the brain via projections from the locus coruleus (LC). The purpose of the LC is to modulate arousal states and adaptive behaviour. In stressful conditions and PTSD we get a large release of noradrenaline in the prefrontal cortex. What can this do to a patient in this example?
1 - dampen cognitive function
2 - dampen cognitive function due to hyper-sensitisation
3 - enhance cognitive function due to hyper-sensitisation
4 - enhance cognitive function due to desensitisation
1 - dampen cognitive function
- impaired cognitive function due to too much stimulus
- too much stimulation, similar to a mini seizure
Where do serotonergic receptors which can be inhibitory like GABA originate from in the brain?
1 - nucleus accumbens
2 - ventral tegmental
3 - locus coeruleus
4 - raphe nuclei
4 - raphe nuclei (Greek: ῥαφή, “seam”)
- a moderate-size cluster of nuclei found in the brain stem
The serotonergic receptors, which are inhibitory like GABA originate from the raphe nuclei (Greek: ῥαφή, “seam”), a moderate-size cluster of nuclei found in the brain stem. If a patient has a lot of serotonin, is this a good or bad thing for patients with anxiety and PTSD?
- good as serotonin reduces neuronal activity
- selective serotonin re-uptake inhibitors (SSRIs) are used to increase serotonin levels
- effective treatment in anxiety and depression where serotonin levels are low
The noradrenergic and serotinergic receptors do opposing roles in the brain. In anxiety disorders it has been suggested that there is an imbalance between the noradrenergic and serotinergic systems. Which is increased and decreased in anxiety disorders?
- increased = noradrenergic
- decreased = serotinergic
What type of receptors are GABA-A receptors?
1 - GPCR Gai
2 - ligand gated receptors (GABA-a)
3 - voltage gated ion channels
4 - receptor tyrosine kinase
2 - ligand gated receptors (GABA-a)
- GABA binds at A site on receptor, opens channel and Cl- floods in
- hyperpolarisation occurs and reduces neuronal activity
GABA-A receptors are ligand gates receptors, where GABA binds at the A site of the GABA ligand gated channel receptor. The channel opens and Cl- floods in, reducing the chance of an action potential. If a patient is prescribed a benzodiazepines (core drug is Diazepam), what happens to the level of activation of the GABA receptors?
- increased activation so inhibit neurons
- bind to GABA-A binding site, BUT different to GABA
- this is why we can increase the effect of GABA
- diazepam is the core drug
In the image we can see a Positron emission tomography (PET) scan of a control and a patient with a panic disorder. The PET study used a ligand that was able to bind with benzodiazepine binding site (GABA-A). What does this image tell us about panic disorders?
- patients with panic disorder have fewer benzodiazepine binding sites
- could indicate lack of sufficient inhibitory control (via GABA) in cortical and limbic regions to suppress inappropriate fear responses causing a panic attack (like a bath with no stop on the tap (GABA) the increased stimulus causes increased neuronal activity
In a similar way to the substantia nigra atrophying in parkinsons disease, there is some evidence to show that there is atrophy combined with hyperactivity of the amygdala. There are also some changes in the hippocampus, which is involved in the negative feedback of the hypothalamus, ultimately modulating the levels of cortisol (stress hormone) in the body. What can chronic stress do to the hippocampus?
- induce cytotoxicity, causing atrophy
- increased levels of cortisol result ion excessive levels of Ca2+ in hippocampus neurons
- increased Ca2+ causes excitotoxicity causing cell death
In a similar way to the substantia nigra atrophying in parkinsons disease, there is some evidence to show that there is changes in the amygdala. There are also some changes in the hippocampus, which is involved in the negative feedback of the hypothalamus, ultimately modulating the levels of cortisol (stress hormone) in the body. Chronic stress causes excessive levels of cortisol in the body, increasing Ca2+ in hippocampus neurons, ultimately leading to excitotoxicity causing cell death, as demonstrated in PTSD. If the hippocampus become damaged in chronic stress what happens to the cortisol levels?
1 - nothing hippocampus is not involved
2 - no negative feedback in hippocampus, so no inhibition of hypothalamus
3 - increased negative feedback so cortisol levels drop
4 - negative feedback causes a drop in cortisol levels acting on hypothalamus
2 - no negative feedback in hippocampus, so no inhibition of hypothalamus
- cortisol levels go unchecked by the hippocampus
- excessive cortisol and chronic stress continues
Cognitive behavioural therapy (CBT) is a talking therapy that can help you manage your problems by changing the way you think and behave. What are the 3 main components of CBT?
1 - fears, feelings, thoughts
2 - fears, feelings, behaviours
3 - feelings, thoughts, behaviours
4 - feelings, behaviours and fears
3 - feelings, thoughts, behaviours
- change in one can affect all 3
