S10) Anxiety Disorders

Question 1

Why is the stress response important?

Answer 1

causes a feeling of anxiety to enable us to escape from potentially dangerous situations.

Question 2

What is the stress response to allow us to get away from threat mediated by?

Answer 2

1. limbic system (neural elements of the stress response)
2. limbic-hypothalamo-pituitary- adrenal axis (endocrine elements of the stress response where the limbic system is able to act on the hypothalamus to stimulate secretion of stress hormones)

Question 3

What is the limbic system?

Answer 3

• The limbic system is a set of brain structures located on both sides of the thalamus, immediately beneath the cerebrum
• It supports a variety of functions including emotion, behavior, motivation, long-term memory, and olfaction

Question 4

Identify the components of the limbic system

Answer 4

• Hippocampal formation
• Septal area
• Amygdala
• ± Prefrontal cortex
• ± Cingulate gyrus

Question 5

Briefly outline the functioning of the limbic system

Answer 5

Hypothalamus - key organ related to stress response - releases CRH - corticotropin releasing hormone - key -links to SNS activation and wider effects via cortisol release.

Question 6

Describe the structure of the hippocampus.

Answer 6

– Curved piece of cortex

– Folded into medial surface of temporal lobe

– Occupies floor of temporal horn of lateral ventricle

– Three parts: subiculum, hippocampus proper, dentate gyrus

Question 7

What is the function of the hippocampus?

Answer 7

Involved in memory and expressions of emotion

Question 8

Describe the inputs and outputs of the hippocampus.

Describe what it leads to.

Answer 8

Inputs from: many parts of the cortex and processes their emotional content

Output: to the thalamus (and hence back to the cortex – the Papez circuit) and also to the hypothalamus (causing autonomic features of emotional responses, since the hypothalamus send projections down through the cord to autonomic preganglionic neurones – the hypothalamospinal tract.

This will lead to sympathetic nervous system activation, as well as release of adrenaline from the adrenal medulla – the acute stress response)
o Role in memory – already discussed
→ Papez circuit may be involved in memory consolidation

Question 9

Describe the structure of the amygdala?

Answer 9

– Almond shaped structure sitting near the tip of the hippocampus

– Buried in the roof of lateral ventricle

– Collection of nuclei

Question 10

What are the inputs and outputs of amygdala?

Answer 10

Inputs of sensory information, brainstem, thalamus, cortex

Outputs to cortex, brainstem and hypothalamus

Question 11

What is the function of the amygdala?

Answer 11

Drive related behaviours and processing of associated emotions

Like the hippocampus, it is involved in behavioural and autonomic emotional responses

Question 12

What is the function of the prefrontal cortex and anterior cingulate gyrus?

Answer 12

Both have modulatory effect on processes associated with the hypothalamus

Prefrontal cortex (classically not part of the limbic system but definite roles in emotion)
o Modulation of emotional responses (e.g. consciously suppressing features of anxiety)
o ‘Perception’ of emotion?

Question 13

Briefly outline the limbic-hypothalamo- pituitary-adrenal axis

Answer 13

Question 14

In the activation of a stress response, what does the SNS activation result in?

Answer 14

Increased heart rate and force of contraction

Dilated bronchi

Question 15

Endocrine elements of the stress response
• The limbic system is able to act on the hypothalamus to stimulate the secretion of stress hormones via the familiar hypothalamo-pituitary-adrenal axis

Describe the HPA axis.

Answer 15

Release of cortisol from the adrenal cortex is part of
the ‘chronic’ stress response

Question 16

What are the actions of cortisol?

Answer 16

• Increase of energy metabolite levels
• Suppression of immune system
• Inhibition of allergic and inflammatory processes

Question 17

Describe the fight or flight response.

Answer 17

Question 18

What is the general adaptation syndrome referring to?

Answer 18

The general adaptation syndrome refers to three stages that the body goes through
during prolonged exposure to stressors

Question 19

What are the three components of the general adaptation syndrome?

Answer 19

Stage 1 - the alarm reaction

Stage 2 - Resistance (effect of adrenaline starts to wear off)

Stage 3 - Exhaustion (when you cannot escape an ongoing stressor)

Question 20

Which three process occur in the alarm reaction part of general adaptation syndrome?

Answer 20

• NA release from sympathetic nerves
• Adrenaline and NA release from adrenal medulla
• Cortisol release from adrenal cortex

(Release of adrenaline and cortisol as well as sympathetic activation)

Question 21

What occurs in the resistance part of general adaption syndrome?

Answer 21

Resistance – action of cortisol is longer lasting than adrenaline, allows maintenance of response to stress

Resistance (effect of adrenaline starts to wear off)

Chronic stress response, prolonged release of cortisol

Question 22

What occurs in the exhaustion part of general adaptation syndrome?

Answer 22

Exhaustion – prolonged stress causes continued cortisol secretion, leading to muscle wastage, suppression of immune system and hyperglycaemia

(when you cannot escape an ongoing stressor)

Chronic side effects of prolonged cortisol secretion start to occur

Question 23

What is anxiety?

Answer 23

Anxiety is a feeling of worry, nervousness or unease about something with an uncertain outcome

Anxiety is the term used for a pathological stress response

Question 24

Why do we get anxious?

Answer 24

– part of normal/ necessary thing esp with linkage to threat

– has an evolutionary process, makes us safer?

need to be anxious to get away from a threat

Question 25

What are the symptoms of anxiety?

Answer 25

Symptoms – primarily attributable to sympathetic activation - Palpitations - Sweating - Trembling/ shaking - Difficulty breathing - Chest pain - Dry mouth - Nausea or abdominal distress (e.g. butterflies in stomach) - Feeling dizzy, unsteady, faint or light-headed

Question 26

So when does the stress response become a problem? (it is usually a normal thing for evolutionary necessity and safety- to run away from a threat)

Answer 26

**When you can't run away** **The stress response can become pathological when you cannot escape a stressor(s), or when ‘trivial’ stressors elicit a strong stress response. However, patients with anxiety disorders may go through all of the stages above** * when it is a psychological threat e.g. social embarrassment, fear of having a panic attack, fear of failing - more of a cognitive involvement resulting to same effects of stress response, if anything exaggerated

Question 27

What is the stress performance curve?

Answer 27

Stress is an inevitable part of life - it is a subjective experience when you feel a demand is placed upon you it can be good for you in terms of completing work/ tasks - gets you more focussed - optimal stress but too much stress - overload - too much arousal/ prolonged stress → can become exhausting and can trigger adverse reactions - chronic release of steroid hormones can also have physical effects

Question 28

Identify six different types of anxiety disorders

Answer 28

- Social phobia • Anxiety about being in social situations - Specific phobias • Spiders, heights etc - Generalised anxiety disorder • Persistent anxiety about a variety of things - Panic disorder • Recurrent, unexpected panic attacks (severe episodes of acute stress response) - Obsessive compulsive disorder (OCD) - Post-traumatic stress disorder (PTSD)

Question 29

Describe the pathophysiology of anxiety disorders.

Answer 29

– Unclear – Equivocal findings in studies of brain activation patterns – GABA levels appear to be low in some anxiety disorders (maybe explaining action of benzodiazepines) – Increasing serotonin levels can help treat anxiety disorders (mechanism unclear, but hippocampus may be involved)

Question 30

In terms of the functional neuro-imaging, explain the effect of common anxiety disorders on the following parts of the brain: - Amygdala - Cingulate cortex - Hippocampus

Answer 30

- (+) Increased function - (-) Decreased function - (-/+) Both increased and decreased function - (?) Too little information

Question 31

What is GABA?

Answer 31

GABA is the **main inhibitory** neurotransmitter → inhibits neurotransmission

Question 32

Explain the relationship between GABA levels and anxiety (and the treatment of such)

Answer 32

- **GABA levels are decreased** in cortex in patients with panic disorder - Benzodiazepines **increase GABA transmission** so reduce anxiety

Question 33

Describe the treatment for anxiety disorders.

Answer 33

**Biological:** * Short term benzodiazepines * SSRIs **Psychological:** * Cognitive behavioural therapy o Getting patients to reflect on their feelings/thoughts/behaviours **Social:** * Support groups, charities etc

Question 34

How does Benzodiazepines act to reduce anxiety?

Answer 34

It is an **anxiolytic drug** Benzodiazepines **increase GABA transmission** so **reduce anxiety**

Question 35

Explain the relationship between serotonin levels and anxiety (and the treatment of such)

Answer 35

- **Increased levels of serotonin** (due to SSRIs) may stimulate serotonin receptors in hippocampus - Leads to neuroprotection, neurogenesis and **reduction of anxiety**

Question 36

What is the treatment for anxiety disorders?

Answer 36

Mainstay of treatment is **SSRIs**- can be given to panic and OCD, usually given as an antidepressant

Question 37

How do SSRIs work?

Answer 37

Block the reuptake of Serotonin .: more remain in the synaptic cleft

Question 38

Benzodiazepines should not be used in the long-term of anxiety disorders. In light of this, discuss other treatment options

Answer 38

- SSRIs (mainstay) / pregabalin (GABA analogue) - Cognitive behavioural therapy (SSRIs- e.g. Prozac - response is not instant/ quick - in depression might not see effects till weeks/ months Benzodiazepines - have a quick response)

Question 39

Why are benzodiazepines **not given for long term treatment** for anxiety disorders?

Answer 39

– Benzos - they make you feel good quickly like alcohol - .: you like them – you can get a crave and tolerance of them if you take more of them. - if you do it regularly, u need more and more and build a tolerance of it – you can get withdrawal effects if you stop taking them - of abrupt stop of Benzos **they are effective for short term, but long term wise, you build tolerance and dependency and hard to get off them**.

Question 40

Briefly illustrate the steps involved in cognitive behavioural therapy

Answer 40

v effect non drug based treatment for anxiety

Question 41

What is an obsession? aka intrusive thoughts

Answer 41

An **obsession** is a thought that **persists and dominates** an individual’s thinking despite their awareness that the thought is either **entirely without purpose**, or has persisted and dominated their thinking **beyond the point of relevance** or **usefulness** Often causes great anxiety and guilt Particularly **repugnant** to individual Reflect changes in society

Question 42

What is a compulsion?

Answer 42

A **compulsion** is an obsessional **motor acts** which may result from an obsessional impulse that **leads directly to the action**, or they may be mediated by an obsessional **mental image** or fear *E.g. I need to turn the light switch on and off ten times or my family will die* Acting out a compulsion may relieve the anxiety provoked by its associated obsession, but frequently carrying out the compulsion is also unpleasant

Question 43

Obsessions/ compulsions/ both present on most days for a period of at least 2 weeks. Obsessions and compulsions share some features. Describe four of them

Answer 43

- Originate in the mind of the patient - Repetitive and unpleasant - Acknowledged as **excessive or unreasonable** - Patient tries to resist, but at least one obsession/compulsion is unsuccessfully resisted

Question 44

What is the diagnostic criteria for obsessions / compulsions?

Answer 44

- Carrying out the obsessive thought/act is not itself pleasurable - Obsessions/compulsions must cause distress / interfere with the patient’s social or individual functioning - Obsessions and/or compulsions present on **most days for a period of at least 2 weeks**

Question 45

What is the epidemiology of OCD?

Answer 45

– Fairly common – 1 in 50 will suffer from it at some point in their lives# – 1/3 of cases start between 10 and 15 years of age – ¾ have started by age 30 – Equal prevalence in males and females

Question 46

OCD is primarily characterised by …?

Answer 46

Primarily characterised by **obsessions** and **compulsions**

Question 47

Identify three **suggested** **theories** for the pathophysiology of OCD - .: acc unknown

Answer 47

The pathophysiology is actually unclear but there are some suggested theories. - **Re-entry circuits in basal ganglia** - **Reduced serotonin** (hence why SSRIs tend to help) - **PANDAS** - Altered activity in a range of cortical areas (cause or effect?) - Autoimmune aetiologies o There may be cross-reactivity with certain streptococcal antigens and the basal ganglia

Question 48

What is Tourette's syndrome?

Answer 48

Question 49

In terms of the following layout, illustrate how the normal pathway of the basal ganglia

Answer 49

Question 50

In terms of the following layout, illustrate how the pathophysiology of OCD might be due to re-entry circuits in the basal ganglia

Answer 50

– The cortex projects to the basal ganglia, and these then project back up to the cortex via the thalamus – This is an example of a ‘re-entrant’ loop, where obsessional thoughts can re-enter the cortex having entered the basal ganglia – This may be due to overactivity in the direct pathway – Treatments that inhibit thalamic (and hence cortical) activity by reducing the direct pathway or increasing the indirect pathway may hold promise (e.g. subthalamic nucleus stimulation)

Question 51

What is PANDAS?

Answer 51

**Paediatric autoimmune neuropsychiatric disorder associated with streptococcal infection** is a hypothesis that children develop OCD / tic disorders due to group A beta-hemolytic streptococcal infections

Question 52

Describe the onset, presentation, cause and treatment of PANDAS

Answer 52

- **Onset**: sudden onset of OCD symptoms or tics after infection with Group-A beta-haemolytic strep - **Presentation**: dramatic onset of psychiatric or behavioural problems - **Cause**: antibodies ‘cross-react’ with neurons in basal ganglia, causing symptoms - **Treatment**: Antibiotics and usual OCD management

Question 53

Describe the treatments for OCD.

Answer 53

**Biological:** – High dose SSRIs +/- antipsychotics – Deep brain stimulation **Psychological:** – Cognitive Behavioural Therapy (CBT) and variety of other interventions **Social:** – Family support – Groups etc.

Question 54

Briefly illustrate how OCD is treated with cognitive behavioural therapy

Answer 54

**Cognitive behavioural therapy** – exposure response prevention expose them to the thoughts and feelings and then they don't do the response - not appealing to them at the beginning, do this gradually. gradually lessens - process of habituation or extinction learning.

Question 55

Describe the pharmacological treatment of OCD

Answer 55

- High dose SSRIs (higher dose + longer treatment course than depression) - (sometimes) Augmentation with antipsychotics (don't just block dopamine but also have effects other) *e.g. clomipramine (Tricyclic antidepressant - TCA)* - sig blocks serotonin reuptake

Question 56

What is deep brain stimulation?

Answer 56

– where you have electrodes placed deep within the brain – deep promising results but v small numbers in trials **NON- ABLATIVE** (DOESN'T DESTROY PARTS OF BRAIN TISSUE) PROCEDURE (EMERGING THERAPEUTIC APPROACHES- NOT FIRST LINE THERAPIES)

Question 57

PSYCHOSURGERY FOR OCD - i don't think we need to know this!

Answer 57

NOT SUPPORTED BY NICE GUIDELINES DOUBTS ABOUT EFFICACY

Question 58

What is PTSD?

Answer 58

- **Post-traumatic stress disorder** is an anxiety disorder caused by very stressful, frightening or distressing events - It occurs **within 6 months** of a traumatic event of **exceptional severity** e.g. rape, battlefield trauma

Question 59

What characterises PTSD?

Answer 59

- Evidence of trauma - causes repetitive, intrusive recollection or re-enactment of the event in memories, daytime imagery, or dreams - There is a conspicuous emotional detachment, numbing of feeling, and avoidance of stimuli that might arouse recollection of the trauma (re-experiencing the experience)

Question 60

Describe the pathophysiology of PTSD

Answer 60

Pathophysiology is actually **unclear** but suggested theories: - **Hyperactivity of amygdala –** causing exaggerated response to perceived threat - **Lower cortisol level –** hence, ↓ inhibition of traumatic memory retrieval and sympathetic response

Question 61

How can PTSD be treated?

Answer 61

**Biological:** **Medical treatment** – same as other anxiety disorders – some SSRIs – maybe short term benzodiazepines **Psychological:** – Cognitive behavioural therapy – Eye Movement Desensitisation Reprocessing (EMDR) - type of CBT - get ppl to go back to the memory even though they don't like it and get them to hold it in a particular way so they have a form of exposure to it in order to process that memory - .: facilitating their processing of the memory In conventional CBT- we do it with narratives in EMDR - get them to follow your fingers - evidence that it speeds up processing, unknown cause behind it **Social:** – Charities are particularly active, such as ‘Help for Heroes’