Depression

Question 1

What are the risk factors for depression?

Answer 1

• Personal/family psychiatric history (major depression might result from a polygenic disorder)
• Loss of a parent in childhood
• Abuse in childhood
• Use of alcohol, nicotine and recreational drugs
• Anxiety and panic syndrome
• Stress in the workplace
• Household type and composition
• Recent threatening life events
• Puberty, pregnancy and perimenopause in women

Question 2

Way are the three core features of depression?

Answer 2

• Pervasive low mood
• Loss of interest and enjoyment (anhedonia)
• Reduced energy, diminished activity

Question 3

What are the ‘other features’ of depression?

Answer 3

• Poor self-esteem, self-confidence, self-control
• Negative view of past, present and future
• Fatigue
• Disturbed sleep (terminal insomnia)
• Diminished (or increased) appetite
• Poor concentration and attention
• Ideas or acts of self harm or suicide
• Feelings of helplessness

Question 4

How are the different severities of depressive disorder differentiated?

Answer 4

• Dysthymia: a few mild but persistent symptoms leading to a persistent low grade condition
• Depressive disorder: more numerous and more severe symptoms
• Severe depression: psychotic symptoms (delusions, hallucinations) or depressive stupor

Question 5

What areas of the brain are involved in depression and how are these related to the Papez circuit?

Answer 5

Brain areas involved in depression symptoms are:

• the lymbic system (recall, emotions)
• higher cortical areas (reasoning, cognition)
• hypothalamus-pituitary axis (stress)

These broadly map on the Papez circuit, involved with the experience and expression of emotion, and a more updated version of it, which includes the amygdala.
This circuitry is influenced by the monoamine neutransmitter systems.

Question 6

How do life stressful events impact upon monoaminergic systems?

Answer 6

• Stress activates HPA causing CRF release and production of glucocorticoids.
• Glucorticoids regulate components of the monoaminergic systems (receptors, transporters) and contribute to the modification of limbyc system structural connessions.
• Important to remember: not everyone with stress becomes depressed and someone with no stress can become depressed. Each individual reacts differently to the environment, with genetic and developmental factors contributing differentially to the onset or not of depression

Question 7

What does the amygdala do?

Answer 7

Best known for its role in conditioned fear.

Fear related information enters the amygdala its basal and lateral nuclei

and leaves it via its central nucleus whose projections go toward the hypothalamus, central monoaminergic nuclei, PAG.

It is also important for conditioned responses to rewarding stimuli.

Question 8

How is the amygdala thought to be involved in depression?

How might antidepressants be modulating brain function?

Answer 8

It has recently been shown that:

• following antidepressant treatment there is increased coupling between the amygdala and right lateral prefrontal cortex which might facilitate the prefrontal modulation of amygdala activity.

Antidepressants may increase corticolimbic coupling and enhance the cortical regulation of abnormal limbic activation. (Chen, 2007)

Question 9

In what proportion of depressed patients is there excessive activation of the HPA axis?

Answer 9

Excessive activation of the HPA axis is seen in half of depressed patients.

Question 10

What neural circuits are you aware of possibly being involved in depression ?

Answer 10

• GABAergic
• glutamergic
• dopaminergic
• peptidergic
• noradrenergic
• seratonergic

Question 11

See tutorial lecture for some useful diagrams etc.

Answer 11

-

Question 12

What is the monoamine hypothesis of mood disorders (specifically with regard to depression)?

Answer 12

Depressed: decreased concentration of monoamines is thought to be the cause of depression

(Blockade of re-uptake restores normal monoamine levels thus ameliorating mood)

Question 13

4 ascending monoamine NT systems?

Answer 13

NA

DA

Ach

5-HT

Question 14

What class of drug is amitriptyline and how does it work?

Answer 14

Tricyclic antidepressant

Block uptake of 5-HT, NA (+DA)

Question 15

What class of drug is fluoxetine (prozac) and how does it work?

Answer 15

Selective seratonin reuptake inhibitor (SSRI)

Blocks uptake of 5-HT > NA (> DA)

Question 16

What class of drug is veulafaxine and how does it work?

Answer 16

Seratonin and noradrenaline reuptake inhibitor (SNRI)

Blocks uptake of 5-HT = NA (>DA)

Question 17

What class of drug is reboxitine and how does it work?

Answer 17

Selective noradrenaline reuptake inhibitor (NSRI)

Blocks reuptake of NA > 5-HT (>DA)

Question 18

What class of drug is phenelzine and how does it work?

Answer 18

Monoamine Oxidase (MAO) inhibitor

Increases availability of 5-HT, NA (and DA)

Question 19

What class of drug is moclobemide and how does it work?

Answer 19

Reversible inhibitor of MAO (RIMA)

Increases availability of 5-HT, NA (and DA)

Question 20

What class of drug is Mirtazepine and how does it work?

Answer 20

Atypical drug
- release enhancer?

Inhibition of presynaptic alpha2 receptors - to enhance amine release (also block 5-HT2, 5-HT3)