Anxiety and Depression Flashcards
Define anxiety disorder.
An anxiety disorder is an inappropriate or excessive anticipatory manifestation of the fear response.
List 4 responses typical of anxiety disorders.
Responses of anxiety disorders include:
1 - Defensive behaviours.
2 - Autonomic reflexes.
3 - Corticosteroid secretions.
4 - Negative emotions.
List 3 types of anxiety disorder.
Types of anxiety disorder include:
1 - General anxiety disorder.
2 - Phobic anxiety.
3 - Panic disorder.
Which endocrine axis is involved in the stress response?
Describe this axis.
List 2 conditions in which this axis is impaired.
- 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).
What is the source of input to the hypothalamus to trigger the hypothalamic-pituitary-adrenal axis in response to stress?
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.
List 2 physiological abnormalities in the stress response in individuals suffering from anxiety disorders and major depressive disorder.
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.
List 3 treatments of anxiety disorders.
1 - Psychological, e.g. CBT.
2 - Prescribed medications.
3 - Self-medication (alcohol, cannabis etc.).
Give an example of a potential mechanism for psychological treatments for anxiety disorders.
Psychological treatments might reverse neuroplastic changes in the Papez circuit.
List 2 factors that determine the choice of anxiolytic drugs (drugs for treating anxiety disorders).
1 - Nature of predominant symptoms.
2 - Duration of treatment needed.
List 3 anxiolytic drug classes.
1 - Beta antagonists.
2 - Benzodiazepines.
3 - Monoaminergic drugs.
Describe the mechanism of action of beta antagonists for the treatment of anxiety disorders.
For which type of anxiety disorder are they most useful?
- 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.
Give an example of an effect of benzodiazepines other than anxiolysis.
Benzodiazepines are hypnotic (sleep-inducing) as well as anxiolytic.
Briefly describe the mechanism of action of benzodiazepines.
Benzodiazepines bind to benzodiazepine allosteric sites on GABA receptors to enhance the action of GABA, increasing Cl- influx upon GABA binding.
List 2 structures of the limbic system that are affected by benzodiazepines.
1 - Prefrontal cortex.
2 - Amygdala.
*GABA receptors are ubiquitous in the brain so benzodiazepines aren’t specific to the limbic system.
What is the combined effect of benzodiazepines and alcohol?
The combined effect of benzodiazepines and alcohol is respiratory depression.
What is the recommended duration of benzodiazepine use?
The recommended duration of benzodiazepine use is <4 weeks.
List 5 effects of benzodiazepine withdrawal.
Effects of benzodiazepine withdrawal include:
1 - Anxiety.
2 - Tremor.
3 - Seizure.
4 - insomnia.
5 - Depression.
List 3 benzodiazepines.
Examples of benzodiazepines:
1 - Diazepam.
2 - Nitrazepam.
3 - Midazolam.
Give an example of a monoaminergic drug class.
List 4 drugs within this class.
- 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.
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?
- Buspirone is a monoaminergic drug that is not classed as an SSRI.
- The mechanism of action is unknown.
List 4 symptoms of major depressive disorder.
1 - Misery.
2 - Loss of motivation.
3 - Loss of appetite.
4 - Suicidal thoughts.
What proportion of cases of major depressive order is reactive (to some stimulus) and what proportion is endogenous?
- 75% of cases of major depressive disorder are reactive.
- 25% are endogenous.
What is the monoamine theory of depression?
The monoamine theory of depression suggests that depression is due to hypoactivity at monoaminergic synapses in the brain.
List 3 treatments for depression.
1 - Antidepressant drugs (monoaminergic drugs).
2 - Psychotherapy (as with anxiety).
3 - Electroconvulsive therapy (inducing currents in the brain to induce a brief seizure).
What is the physiological effect of antidepressant drugs?
How long do antidepressant drugs take to work?
- Antidepressant drugs rapidly increase monoamines in the brain.
- Despite this, the drugs take 1-3 weeks to have an effect on symptoms.
List the classes of antidepressant drugs.
List the classes in order of side effect intensity from strongest to weakest.
1 - Selective serotonin reuptake inhibitors (SSRIs).
2 - Tricyclic antidepressants (TCAs).
3 - Monoamine oxidase inhibitors (MAOIs).
List 3 side effects of selective serotonin reuptake inhibitors (SSRIs).
1 - GI symptoms (nausea / vomiting).
2 - Weight changes.
3 - Suicidal thoughts.
Give an example of a monoamine oxidase inhibitor (MAOI).
Moclobemide.
Which type of monoamine oxidase enzyme is targeted by moclobemide?
Why is this advantageous?
How strongly does moclobemide bind to monoamine oxidase?
- Moclobemide selectively binds to monoamine oxidase-A.
- This is advantageous because MAO-A handles serotonin in particular.
- Moclobemide binds reversibly to the enzyme.
List 3 side effects of monoamine oxidase inhibitors (MAOIs).
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.
Give an example of a tricyclic antidepressant.
Amitriptyline.
Briefly describe the mechanism of action of tricyclic antidepressants.
Tricyclic antidepressants inhibit the reuptake of both serotonin and noradrenaline.
List 2 side effects of tricyclic antidepressants.
1 - Antimuscarinic effects.
2 - Sedation (due to H1 receptor antagonism - remember histamine has a role in sleep).
Give an example of a newer antidepressant drug.
Briefly describe the mechanism of action of this drug.
- Agomelatine is a new antidepressant drug.
- It is a melatonin receptor agonist which adjusts the circadian rhythm.
Describe the network hypothesis of depression.
- 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.
How is the network hypothesis of depression explained by changes in the neuroendocrine stress response (HPA axis)?
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.
How might the network hypothesis of depression explain the 1-3 week latency for antidepressant drugs?
- 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.
