neuro: anxiety

Question 1

what does anxiety mean?

Answer 1

anxiety is a feeling of unease (worry or fear) which can range from mild to severe

Question 2

anxiety can be an innate adaptive response and a learned adaptive response. Explain this.

Answer 2

• innate: fear is an adaptive response to a threatening response.
  Fear responses compromise of several types: defensive behaviours, autonomic responses and increased alertness. Example someone throwing something directly at your face

Learned: fears can be learned through life experiences, ex: touching a hot stove. Fear response can occur in an anticipatory manner, sometimes independently of the stimuli.

Question 3

what is intermittent and chronic anxiety?

Answer 3

intermittent: triggered due to certain events, and situations
chronic: irrational, leading to social disturbances, avoidance behaviours, excessive worry and concentration/memory issues

Question 4

what are some physiological and psychological symptoms?

Answer 4

psychological:
-stress
-suspense
-agitated

Physiological:
- tachycardia
-shortness of breath
- pins and needles
-shaking and sweating

Question 5

what can cause symptoms of anxiety?

Answer 5

-past experiences
-everyday life and habits (money concerns, academia etc)
-diet
-physical and mental health
-alcohol and drugs can trigger anxiety like symptoms

Question 6

why does alcohol trigger anxiety like symptoms?

Answer 6

• alcohol is a CNS depressant; increases GABAergic neurotransmission and can block glutamatergic neurotransmission.
  -balance between glutamate and GABA is crucial for an optimal brain function: alcohol disrupts this balance
• our brains adapt to counteract this inbalance- leads to low levels of GABA and high levels of glutamate, which can trigger anxiety symptoms.

Question 7

what can be derived from genetic studies about anxiety disorders?

Answer 7

• anxiety disorders are not based on one single gene, but likely have a more complex genetic basis which can be affected by environmental factors.

Question 8

explain the pathophysiology of anxiety?

Answer 8

• the stress response is regulated by the HPA axis. (Hypothalamus pituitary adrenal axis)
  -HPA regulates the release of cortisol (a glucocorticoid) which contributes to the bodies physiological response to stress.
• an experiment was done in rodents that proved that CRH (corticotopin releasing hormone) plays a key role in regulating the stress response
• overexpression of CRH -> increased anxiety like behaviours

-knocking out CRH receptors -> less anxiety like behaviours

Question 9

what brain regions can influence the HPA axis and it’s level of activity?

Answer 9

• amygdala and hippocampus
• amygdala - role in emotion and fear response
  -stimulates HPA axis, promotes cortisol release
  -hyperactivity of amygdala linked to anxiety disorders

hippocampus: suppresses HPA axis, prevents release of cortisol
- hippocampus under activity is linked to anxiety disorders.

Question 10

what is the DSM-5 2013 classification of anxiety disorders?

Answer 10

-diagnostic and statistical manual of mental disorders
classified into:

-anxiety disorders
-OCD (obsessive compulsive disorders)
-trauma and stressor related disorders

Question 11

what do classifications of the anxiety disorders include?

Answer 11

Anxiety disorders:
-generalised anxiety disorder
-specific phobias
-social phobias
-panic disorders

OCD:
Body dysmirohic disorder
-hoarding disorder
-trichotillomania (hair pulling disorder)

Trauma and stressor related dusorders:
-PTSD

Question 12

explain generalised anxiety disorder?

Answer 12

• characterised by an ongoing state of extreme anxiety lacking clear reason or focus

Associated with three or more of these 6 symptoms:

• restlessness
  -fatigue
• increased muscle archness or soreness
• impaired concentration
• irritability
• difficulty sleeping

These symptoms should not be classified as generalised anxiety disorder if the symptoms are due to substance abuse or better explained by another anxiety disorder

GAD sufferers symptoms are likely to be different from another persons experience with GAD

Question 13

explain specific phobias?

Answer 13

extreme fears if anxieties due to exposure to a particular situation or object - leads to avoidance behaviours.
- phobia is persistent and typically persists for atleast six months, impairs activities of daily living.

Question 14

explain social phobias?

Answer 14

• significant anxiety provoked by exposure to certain types of social or performance situations.
  -includes social interactions, being observed and performing in front of others.
  -phobia is persistent for at least six months and impairs activities of daily living
  Not attributable to a substance or mental condition or better explained by another type of anxiety disorder

Question 15

what is panic disorder?

Answer 15

• characterised by recurring panic attacks, without a seemingly clear cause or trigger
• a panic attack is an abrupt surge of intense fear or discomfort reaching a peak within mins
  -associated with four or more of thirteen symptoms:

Symptoms are: increased heart rate, sweating/trembling/shaking, shortness of breath and fear of dying

-individual worries about further panic attacks which may lead to another panic attack- panic cycle
- panic attacks can either occur spontaneously, or be a feature of a number of different anxiety disorders

Question 16

what is OCD?

Answer 16

• characterised by compulsive behaviour driven out of irrational anxiety
• as it is called ‘obsessive compulsive disorder’ this consists of 2 actions: obsession and compulsion

obsession: recurrent intrusive/impulsive thoughts or ideas
Compulsions: repetitive behaviours or mental acts that are performed to reduce anxiety associated with the obsessions.
- obsessions and compulsions are time consuming (taking up over an hour of your day), impairing activities of daily living

Question 17

explain PTSD?

Answer 17

• characterised by distress triggered by the recall of past traumatic experiences
  -triggered by exposure to certain situations; actual or threatened death, serious injury or sexual violence
• exposure may be direct, as a witness or learning that a close family member or friend experienced the traumatic event.
  -associated with one or more intrusion symptoms:
  -recurrent intrusive memories
  -nightmares
  -dissociative reactions (eg flashbacks)
• psychological and physiological distress at exposure to cues resembling the traumatic event
  -disturbances persist for atleast one month, imparting activities of daily living

Question 18

what are some psychological and pharmacological treatments for anxiety?

Answer 18

psychological: cognitive behavioural therapy

pharmacological: anxiolytics

Question 19

what are anxiolytics?

Answer 19

anxiolytics are a class of drugs used to treat anxiety disorders

Question 20

what are benzodiazepines and where do they bind?

Answer 20

-benzodiazepines are a class of GABA a receptor positive allosteric modulators
-they bind at a distinct site on the GABA a receptor
-when benzodiazepine binds, it increases the affinity of GABA to its own binding site, and produces a general enhancement of its neuroinhibitory actions. benzodiazepines stabilise the GABAa receptor for GABA once in the ‘open configuration’.
-GABA a receptor is the key target for anxiolytics
- the benzodiazepine binding site is present in between the alpha and gamma subtype
-therefore benzodiazepines are known as ‘positive allosteric modulators’. They are a cleaner compound compared to barbiturates, as they do not activate other receptors.

Question 21

examples of benzodiazepines?

Answer 21

midazolam: ultrashort (6 hours) —-> anaesthetic

lorazepam: short (12-18 hours) —> anxiolytic, anti convulsant

aprazolam: medium (24 hours) —> anxiolytic (ex xanax)

diazepam: long (24-48 hours) —-> anxiolytic, anti convulsant

Question 22

how do benzodiazepines contribute to tolerance and withdrawal?

Answer 22

if you take benzodiazepines, you have an increased amount of activity at the GABA A receptors
if you keep taking benzodiazepines, you can develop tolerances, a theory as to why this may happen is bc you get neuroadaptations occurring at the brain.

The brain tries to balance the activity between the inhibitory and excitatory activity in the brain.
How they do this is additional glutamate receptors may be trafficked to the post synaptic neurone to try and re address the balance.
Due to the increased activity at the glutamate receptors, the individual has to take more dose of benzodiazepines to balance out the excitatory activity and relive their symptoms of anxiety.

If someone were to go cold Turkey and stop taking benzodiazepines, there wld be a reduced activity at GABA a receptors and a higher one at the excitatory. Severe side effects will occur such as increased symptoms of anxiety, seizures and could even lead to death.

Question 23

overview on 5-HT?

Answer 23

• serotonin is a neurotransmitter in the PNS and CNS
• serotonin activates g-coupled protein subtypes (5HT1-7) with the exception of ligand gated ion 5-HT3
  -it’s function is involved in sleep and wakefulness in addition to mood and behaviours
  -serotonin is a key drug target for depression and anxiety disorders

Question 24

what are 5-HT 1a receptor agonists?

Answer 24

• 5-HT 1a receptor agonists (ex buspirone) are a class of drugs primarily used for treating generalis3 anxiety disorders.
  -buspirones side effects are less severe compared to benzodiazepines however they do include dizziness, nausea headache etc.

Question 25

how does buspirone work?

Answer 25

-it is a 5-HT 1a receptor agonist, therefore it activates the 5-HT 1a autoreceptor, which then causes an inhibition of 5-HT (serotonin) release.

Question 26

why does buspirone decrease serotonin levels for GAD whereas SSRI’s increase serotonin level for more long term anxiety/depression ?

Answer 26

• initially, buspirone activates the auto receptors which therefore blocks the release of 5-HT. however with time, the auto receptors start to desensitise, which leads to the down regulation of the 5-HT 1a auto receptors. The desensitisation and down regulation of the auto receptors results in heightened excitation of serotonergic neurones and increased 5-HT release.

Question 27

overview on noradrenaline?

Answer 27

-a neurotransmitter in the peripheral nervous system and CNS
-noradrenaline activates G protein coupled receptor subtypes: alpha noradrenerguc and beta noradrenergic receptors.
-noradrenaline is the major neurotransmitter in the sympathetic nervous system (ex: cardiovascular tone)
-noradrenaline also has roles in sleep, attention, arousal and wakefulness.
-a drug target for peripheral manifestations of anxiety

Question 28

talk about beta-noradrenergic receptor antagonists?

Answer 28

beta-noradrenergic receptor antagonists (eg propanolol) are a class of drugs that can be used to treat some forms of anxiety.
-betanoadrenergic antagonists reduce some of the peripheral manifestations of anxiety (nothing to do with psychological, more physiological)
- include tachycardia, sweating, tremors and GI problems
- effectiveness is dependant on blocking peripheral sympathetic responses (fight or flight) rather than centra, effects