Anxiety and Depression

Question 1

Define anxiety disorder.

Answer 1

An anxiety disorder is an inappropriate or excessive anticipatory manifestation of the fear response.

Question 2

List 4 responses typical of anxiety disorders.

Answer 2

Responses of anxiety disorders include:

1 - Defensive behaviours.

2 - Autonomic reflexes.

3 - Corticosteroid secretions.

4 - Negative emotions.

Question 3

List 3 types of anxiety disorder.

Answer 3

Types of anxiety disorder include:

1 - General anxiety disorder.

2 - Phobic anxiety.

3 - Panic disorder.

Question 4

Which endocrine axis is involved in the stress response?

Describe this axis.

List 2 conditions in which this axis is impaired.

Answer 4

• The hypothalamic-pituitary-adrenal axis is involved in the stress response:

1 - The paraventricular nucleus of the hypothalamus releases corticotropin-releasing factor (CRF) to stimulate the anterior pituitary.

2 - The anterior pituitary releases adrenocorticotropic hormone (ACTH) to stimulate the adrenal gland.

3 - The adrenal gland produces cortisol, which has an inhibitory effect (negative feedback) on the hypothalamus.

• This axis is impaired in anxiety and depression (it’s in the name of the deck duh).

Question 5

What is the source of input to the hypothalamus to trigger the hypothalamic-pituitary-adrenal axis in response to stress?

Answer 5

The limbic system triggers the HPA axis in response to stress:

• The cortex sends information to the amygdala and hippocampus.
• The amygdala has an excitatory effect on the hypothalamus (triggers the stress response).
• The hippocampus has an inhibitory effect on the hypothalamus (prevents the stress response).
• Remember this circuit is known as the Papez circuit.

Question 6

List 2 physiological abnormalities in the stress response in individuals suffering from anxiety disorders and major depressive disorder.

Answer 6

1 - Cortisol loses its inhibitory effect at the hypothalamus.

2 - Neuroplastic changes in the Papez circuit that precedes the hypothalamus, resulting in a loss of inhibition or increased excitation.

Question 7

List 3 treatments of anxiety disorders.

Answer 7

1 - Psychological, e.g. CBT.

2 - Prescribed medications.

3 - Self-medication (alcohol, cannabis etc.).

Question 8

Give an example of a potential mechanism for psychological treatments for anxiety disorders.

Answer 8

Psychological treatments might reverse neuroplastic changes in the Papez circuit.

Question 9

List 2 factors that determine the choice of anxiolytic drugs (drugs for treating anxiety disorders).

Answer 9

1 - Nature of predominant symptoms.

2 - Duration of treatment needed.

Question 10

List 3 anxiolytic drug classes.

Answer 10

1 - Beta antagonists.

2 - Benzodiazepines.

3 - Monoaminergic drugs.

Question 11

Describe the mechanism of action of beta antagonists for the treatment of anxiety disorders.

For which type of anxiety disorder are they most useful?

Answer 11

• Beta antagonists reduce somatic symptoms, e.g. by reducing heart rate.
• They are most useful for phobic anxiety disorders, as they can be taken in preparation or in response to a particular stressor in the medium-short term.

Question 12

Give an example of an effect of benzodiazepines other than anxiolysis.

Answer 12

Benzodiazepines are hypnotic (sleep-inducing) as well as anxiolytic.

Question 13

Briefly describe the mechanism of action of benzodiazepines.

Answer 13

Benzodiazepines bind to benzodiazepine allosteric sites on GABA receptors to enhance the action of GABA, increasing Cl- influx upon GABA binding.

Question 14

List 2 structures of the limbic system that are affected by benzodiazepines.

Answer 14

1 - Prefrontal cortex.

2 - Amygdala.

*GABA receptors are ubiquitous in the brain so benzodiazepines aren’t specific to the limbic system.

Question 15

What is the combined effect of benzodiazepines and alcohol?

Answer 15

The combined effect of benzodiazepines and alcohol is respiratory depression.

Question 16

What is the recommended duration of benzodiazepine use?

Answer 16

The recommended duration of benzodiazepine use is <4 weeks.

Question 17

List 5 effects of benzodiazepine withdrawal.

Answer 17

Effects of benzodiazepine withdrawal include:

1 - Anxiety.

2 - Tremor.

3 - Seizure.

4 - insomnia.

5 - Depression.

Question 18

List 3 benzodiazepines.

Answer 18

Examples of benzodiazepines:

1 - Diazepam.

2 - Nitrazepam.

3 - Midazolam.

Question 19

Give an example of a monoaminergic drug class.

List 4 drugs within this class.

Answer 19

• Serotonin-selective reuptake inhibitors (SSRIs) are an example of a monoaminergic drug class. They include:

1 - Fluoxetine.

2 - Paroxetine.

3 - Sertraline.

4 - Citalopram.

*These drugs are also used to treat depression.

Question 20

Give an example of a monoaminergic drug that is not a serotonin-selective reuptake inhibitor (SSRI).

What is the mechanism of action for this drug?

Answer 20

• Buspirone is a monoaminergic drug that is not classed as an SSRI.
• The mechanism of action is unknown.

Question 21

List 4 symptoms of major depressive disorder.

Answer 21

1 - Misery.

2 - Loss of motivation.

3 - Loss of appetite.

4 - Suicidal thoughts.

Question 22

What proportion of cases of major depressive order is reactive (to some stimulus) and what proportion is endogenous?

Answer 22

• 75% of cases of major depressive disorder are reactive.

- 25% are endogenous.

Question 23

What is the monoamine theory of depression?

Answer 23

The monoamine theory of depression suggests that depression is due to hypoactivity at monoaminergic synapses in the brain.

Question 24

List 3 treatments for depression.

Answer 24

1 - Antidepressant drugs (monoaminergic drugs).

2 - Psychotherapy (as with anxiety).

3 - Electroconvulsive therapy (inducing currents in the brain to induce a brief seizure).

Question 25

What is the physiological effect of antidepressant drugs?

How long do antidepressant drugs take to work?

Answer 25

• Antidepressant drugs rapidly increase monoamines in the brain.
• Despite this, the drugs take 1-3 weeks to have an effect on symptoms.

Question 26

List the classes of antidepressant drugs.

List the classes in order of side effect intensity from strongest to weakest.

Answer 26

1 - Selective serotonin reuptake inhibitors (SSRIs).

2 - Tricyclic antidepressants (TCAs).

3 - Monoamine oxidase inhibitors (MAOIs).

Question 27

List 3 side effects of selective serotonin reuptake inhibitors (SSRIs).

Answer 27

1 - GI symptoms (nausea / vomiting).

2 - Weight changes.

3 - Suicidal thoughts.

Question 28

Give an example of a monoamine oxidase inhibitor (MAOI).

Answer 28

Moclobemide.

Question 29

Which type of monoamine oxidase enzyme is targeted by moclobemide?

Why is this advantageous?

How strongly does moclobemide bind to monoamine oxidase?

Answer 29

• Moclobemide selectively binds to monoamine oxidase-A.
• This is advantageous because MAO-A handles serotonin in particular.
• Moclobemide binds reversibly to the enzyme.

Question 30

List 3 side effects of monoamine oxidase inhibitors (MAOIs).

Answer 30

1 - Cheese reaction, e.g. increased blood pressure (due to unmetabolised tyramine from cheese, red wine and yeast extracts displaces noradrenaline out of sympathetic neurones as a result of monoamine buildup).

2 - Antimuscarinic effects.

3 - Alpha 1 receptor antagonism.

Question 31

Give an example of a tricyclic antidepressant.

Answer 31

Amitriptyline.

Question 32

Briefly describe the mechanism of action of tricyclic antidepressants.

Answer 32

Tricyclic antidepressants inhibit the reuptake of both serotonin and noradrenaline.

Question 33

List 2 side effects of tricyclic antidepressants.

Answer 33

1 - Antimuscarinic effects.

2 - Sedation (due to H1 receptor antagonism - remember histamine has a role in sleep).

Question 34

Give an example of a newer antidepressant drug.

Briefly describe the mechanism of action of this drug.

Answer 34

• Agomelatine is a new antidepressant drug.

- It is a melatonin receptor agonist which adjusts the circadian rhythm.

Question 35

Describe the network hypothesis of depression.

Answer 35

• The network hypothesis of depression suggests that hyperactivity and sensitisation of the neuroendocrine stress response (HPA axis) due to chronic stress is the cause of depression.
• It also suggests that depression is an exacerbated form of the impaired neuroendocrine stress response seen in anxiety.

Question 36

How is the network hypothesis of depression explained by changes in the neuroendocrine stress response (HPA axis)?

Answer 36

1 - Chronically high levels of cortisol act on the hippocampus (rather than on the hypothalamus directly) to exert an inhibitory effect on the hypothalamus, where there are many cortisol receptors.

2 - Chronic stimulation of cortisol receptors reduces the number of the receptors in the hippocampus.

3 - Chronic stimulation of cortisol receptors also reduces brain-derived neurotrophic factor, which is important for synapse maintenance.

4 - Chronic stimulation of cortisol decreases potential for neurogenesis and neuroplasticity.

Question 37

How might the network hypothesis of depression explain the 1-3 week latency for antidepressant drugs?

Answer 37

• The reduction in neurogenesis and neuroplasticity at the hippocampus is antagonised by the increase in monoamines caused by antidepressant drugs.
• This means that antidepressant drugs restore neuronal networks by restoring neurogenesis and neuroplasticity, which takes 1-3 weeks.