Depression

Question 1

What is depression?

Answer 1

unipolar: common mood disodrer (unhappy mood, less happiness rather than increased sadness), anhedonia, difficulty in concentration (more in slides)

Externally triggered -stronger reaction or with no apparent cause (reactive or endogenous)

Question 2

When is depression pathalogical

Answer 2

• disproportionate symtpoms or prolonged.
• high comorbitidy with other conditions (that are stressors themselves that can cause depression)
• many different pathologies (presents over 200 different ways)

Question 3

what are the costs to society of depression?

Answer 3

• risk of suicide increases 7-15%
• relatives and friends impaced
• productivity costs

Question 4

what are epidemiological factors of depression?

Answer 4

Unipolar: alternates between normal and episodes that last 6-9 months
- reoccur through life and increase in frequency and intensity if not treated
- can end ontheir own tho
15-20% population at any time

women: more likely than men (maybe hormonal things like post partum depression, menopause, ovarian hormones related to cortisol )

Incidence increased over last 50 years and age of onset has decreased.

maybe some genetic influence? maybe not

Question 5

Describe stress and depression?

Answer 5

Depression: stress related disorder, related to anxiety.
- stress and anxiety precede depression

linked to HPA axis and higher cortisol and CRF activities

some poeple are more resiliant to stressors

Question 6

what is CRF?

Answer 6

stress related peptide transmitter that effects limbic regions and stimulates cortisol release

Question 7

what is cushings syndrome?

Answer 7

high levels of glucocorticoids and being more prone to depression

Question 8

what does it mean to have high cort levels?

Answer 8

higher CORT in depressed patients (but not all the time)

Question 9

What is the dexamethasone suppression test?

Answer 9

Show excessive CORT release. Dexamethasone is a synthetic glucocorticoid that suppresses cort in normal people but in depressed patients it can’t suppress it.
- DEX can fool HPA axis at adrenal glands into thiniking there are higher levels of cort and activating negative feedback, so in healthy controls there is a drop.

Negative feedback mechansisms are disrupted in depressed patients.

Question 10

what are neural abnormalities associated with depression?

Answer 10

Increased blood flow in amygdala and ventral medial PFC.

• increased amygdala cause of increased anxiety (may lead to stress and depression)
• aspects may be caused by bad communication between PFC and amygdala (PFC usually tells amyg to tone it down)
• maybe makes everything seem worse, no reappraisal.

This can be revered with antidepressant treatment.
- NE and 5HT input.

Also reduced hippocampal volume (can’t remmeber a time being happy)

Question 11

Describe the glucocorticoid hypothesis… What does early life stress do to these systems?

Answer 11

Stress related neuro-endocrine abnormalities of depression.

• other areas can contribute to HPA axis release of CRF and cortisol
• amyg (stimulates)
• hippo (inhibits)
• pfc (inhibits)

Early life stress increases CRF in hypothalamus, increases amygdala sensitivity to stress and decreases glucocorticoid receptors in hippocampus (which usually act as a negative feedback mechansim)

Question 12

What do high levels of glucocorticoids do to hippocampus?

Answer 12

cause excitotoxicity with sustained levels. (atrophy of hippocampal and PFC neurons which usually turn town stress response)
- impaired hippo and PFC leads to loss of inhibitory regulation of HPA axis (no negative feedback systems)

Could contribute to not remembering a time when they were happy

Antidepressants reduce CRF levels and reverse hipopcampal dendritic loss.

Question 13

Describe HPA axis

Answer 13

hypothalamus releases CRF, pituitary and adrenals are involved in sending feedback information.

Question 14

What are the animal models of depression?

Answer 14

No one model -very heterogenous presentation
Use repeated uncontrollable and unpredictable stressors.

Chronic mild stress: lots of different types over a few weeks

Chronic social defeat: put a submissive rat in a dominant rats cage for a while. Models depression.

Early maternal separation: separated for an hour at first few weeks of life. Change HPA axis perhaps?

Question 15

What are behavioral tests for depression?

Answer 15

FST or Tail suspension

• behavioral despair
• passive coping
• acute antidepressants reduce despair behaviors and increases active coping (different from long term effects in humans

social avoidance: used with social defeat model, moniter how much they avoid conspecifics
- model social withdrawal

Sucrose preferecne:

• model anhedonia (but not the best cause depressed ppl still like stuff they might just not wanna work for it)
• chronic antidepressants reverse this effect.

Question 16

What does early life stressors (materal separation) do to HPA axis?

Answer 16

Increase stress induces cortisol and CRF and greater depressed like symptoms (despair)

• reversed with antidepressents
• but when treatment stops they revert back.

makes HPA axis over- responsive and increases risk of depression.

Question 17

What is the monoamine hypothesis?

Answer 17

Depression is result of abnormal reductions in brain monoamine levels (5ht and NE)

EVIDENCE
- Reserpine (blocks packaging) induces depression
MOA inhibitors (block metabolism) alleviate depression
Tricyclic antidpressant (block reuptake NE and 5HT) imipramine alleviates depression, impulse dependent
Fluoxetine (prozac) SSRI treats depression

Question 18

What are issues with the monoamine hypothesis?

Answer 18

1) increase monoamine levels quickly but long lag between drug treatment and redcution of symptoms (maybe needs longer lasting effects)
2) not all depressed patients respond to these drugs, there is also a large placebo effect (especially in severely depressed patients)
3) depletion of 5ht or NE doesn’t cause a depresive phenotype
4) tryptophan depleted cocktail induces depression in people with remission or with a family history but not healthy subjects. having low serotonin doesn’t just cause depression.