anxiety

Question 1

What is anxiety?

Answer 1

Anxiety can be defined as a feeling of unease (e.g. worry or fear), which can range from mild to severe.

Question 2

Anxiety is an innate response

Answer 2

• Fear is an adaptive response to a threatening stimuli
• Fear response comprises several components (e.g. defensive behaviours, autonomic reflexes, increased alertness)
• Many fears are innate and species specific

Question 3

Anxiety is a learned adaptive response

Answer 3

• Fears can also be learned through life experiences (e.g. not touching a hot stove)
• However, fear is not an appropriate response in all circumstances
• Fear response can occur in an anticipatory manner, sometimes independently of stimuli

Question 4

Negative aspects of anxiety

Answer 4

Social disturbances
Avoidance behaviours
incessant worry
Concentration/memory problems

Question 5

Some physiological symptoms

Answer 5

• Tachycardia
• Shortness of breath
• Excessive sweating
• Trembling or shaking
• Headache and dizziness
• Pins and needles
• Gastrointestinal disturbances
• Nausea
• Fatigue
• Insomnia

Question 6

Some Causes symptoms of anxiety?

Answer 6

Past experiences
Everyday life and habits
Diet
Physical and mental health

Question 7

How alcohol and drugs can trigger anxiety

Answer 7

• Alcohol is a central nervous system (CNS) depressant – increases GABAergic neurotransmission and can block glutamatergic neurotransmission
• Balance between GABA and glutamate crucial for optimal brain function – alcohol disrupts this balance

Question 8

Genetics as a possible cause

Answer 8

• Research has linked genetic factors to several anxiety disorders (e.g. panic disorder)
• However, the only clear result that can be derived from genetic studies is that anxiety disorders are not based on a single gene but likely have a complex genetic basis, which can be affected by environmental factors

Question 9

Balance of GABA and glutamate disrupted by Drugs and alcohol

Answer 9

Our brain adapts to counteract this imbalance – leads to low levels of GABA and high levels of glutamate can trigger anxiety symptoms
•	Recreational drugs of abuse (e.g. psychostimulants) can also trigger anxiety symptoms via mechanisms unique to a drug or class of drugs

Question 10

Stress mechanism

Answer 10

The stress response is the co-ordinated reaction to threatening stimuli:
• The stress response is regulated by the hypothalamus-pituitary-adrenal (HPA) axis
• The HPA axis regulates the release of cortisol (a glucocorticoid), which contributes to the body’s physiological response to stress

Question 11

How anxiety disrupts the stress mechanism

Answer 11

It is evident that the activation of CRH-releasing hormones of the hypothalamus play a key role in regulating the stress response:
• Overexpressing CRH in rodent models lead to increased anxiety-like behaviours
• Knocking out CRH receptors in rodent models leads to less anxiety-like behaviours

Question 12

What does CRH stand for?

Answer 12

Corticotropin-releasing hormone

Question 13

Amygdala’s role in emotion and fear

Answer 13

• Stimulates HPA axis (green) to promote cortisol release
• Amygdala hyperactivity linked to anxiety disorders
too much = anxiety

Question 14

Hippocampus’ role in emotion and fear

Answer 14

• Hippocampus – role in learning and memory
• Suppresses HPA axis (red) to prevent excessive cortisol release
• Hippocampus underactivity linked to anxiety disorders

Question 15

Anxiety disorders

Answer 15

• Generalised anxiety disorder (GAD)
• Specific phobias
• Social phobias
• Panic disorder

Question 16

Obsessive compulsive disorders

Answer 16

Obsessive-compulsive disorder (OCD)
Other disorders include:
Body dysmorphic disorder
Hoarding disorder
Trichotillomania (hair-pulling disorder)

Question 17

Generalised Anxiety disorder (GAD)

Answer 17

Generalised anxiety disorder (GAD) is characterised by an ongoing state of excessive anxiety lacking clear reason or focus.
Excessive anxiety and worry occurring for at least six months, which is difficult to control and impairs activities of daily living
• Associated with three or more (of six) symptoms
• Not attributable to a substance or medical condition or better explained by another type of anxiety disorder
• GAD sufferers’ symptoms likely to be different from another person’s experience with GAD

Question 18

Specific phobias

Answer 18

Specific phobias are extreme fears or anxieties provoked by exposure to a particular situation or object – often leads to avoidance behaviours.

Question 19

Social phobias

Answer 19

• Social phobia may relate to one or more social situations in which the individual is exposed to possible scrutiny by others
• Includes social interactions, being observed and performing in front of others
• Social situations almost always provokes immediate fear or anxiety – this is out of proportion to the actual danger posed by the object or situation
• Phobia is persistent and typically persists for at least six months, impairing activities of daily living
• Not attributable to a substance or medical condition or better explained by another type of anxiety disorder

Question 20

OCD

Answer 20

Obsessions

Recurrent, intrusive thoughts, images, ideas or impulses
Compulsions

Repetitive behaviours or mental acts that are performed to reduce anxiety associated with the obsessions

Question 21

Post-traumatic stress disorder (PTSD)

Answer 21

Post-traumatic stress disorder (PTSD) is 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

Question 22

Anxiety disorder treatment

Answer 22

Psychological - Cognitive behavioural therapy (CBT)

Pharmacological - Anxiolytics

Question 23

Anxiolytic drugs

Answer 23

Anxiolytics are a class of drugs used to treat anxiety disorders.

Question 24

Benzodiazepines

Answer 24

Benzodiazepines are a class of GABAA receptor positive allosteric modulators.
• Benzodiazepines bind to a distinct regulatory site on GABAA receptors
• Benzodiazepines stabilise the GABAA receptor binding site for GABA in the open configuration
• Benzodiazepines therefore increases GABA affinity for its binding site and produces a general enhancement of its neuroinhibitory actions
• Benzodiazepines are therefore classed as positive allosteric modulators

Question 25

Midazolam

Answer 25

Ultrashort (< 6 hours) | Anaesthetic

Question 26

Lorazepam

Answer 26

Short (12-18 hours) | Anxiolytic, hypnotic, anti-convulsant

Question 27

Alprazolam

Answer 27

Medium (24 hours) | Anxiolytic

Question 28

Diazepam

Answer 28

Long (24-48 hours) | Anxiolytic, anti-convulsant

Question 29

Benzodiazepines

Answer 29

Benzodiazepines act as positive allosteric modulators at the GABAA receptor to stabilise the GABAA receptor binding site for GABA in the open configuration. Tolerance This serves to restore the initial imbalance seen in the symptomatic stage. An individual therefore needs to take a higher dose of benzodiazepines to address this new imbalance between inhibitory and excitatory neurotransmission. Withdrawal If the individual suddenly withdraws from taking these high doses of benzodiazepines, there is a sudden decrease in inhibitory GABA neurotransmission. Coupled with increased excitatory glutamate neurotransmission, this can lead to heightened anxiety and various other side-effects

Question 30

5-HT1A receptor

Answer 30

Serotonin (5-HT) is a neurotransmitter in the peripheral nervous system (PNS) and in the central nervous system (CNS).

Question 31

The function of 5-HT receptor

Answer 31

Important roles in sleep and wakefulness, in addition to mood and emotional behaviours

Question 32

5-HT1A receptor function

Answer 32

* Buspirone’s side-effects are less troublesome than benzodiazepines – include dizziness, nausea and headache * Buspirone activates 5-HT1A auto-receptors – this inhibits 5-HT release * Buspirone also inhibits the activation of noradrenergic neurons – decreases arousal reactions

Question 33

Noradrenaline function

Answer 33

* Noradrenaline is the major neurotransmitter of the sympathetic nervous system (e.g. cardiovascular tone) * Noradrenaline also has roles in attention, arousal and sleep and wakefulness

Question 34

Drug noradrenaline function

Answer 34

• A drug target for peripheral manifestations of anxiety (e.g. 𝝱-noradrenergic receptor antagonists)

Question 35

𝛽-noradrenergic receptors antagonists

Answer 35

``` 𝛽-noradrenergic receptor antagonists (e.g. propranolol) are a class of drugs that can be used to treat some forms of anxiety. • Propranolol is non-selective between 𝛽1 and 𝛽2 noradrenergic receptors • 𝛽-noradrenergic antagonists reduce some of the peripheral manifestations of anxiety ``` Include tachycardia, sweating, gastrointestinal problems and tremor