Depression

Question 1

What is depression ?

Answer 1

Affective disorder: extreme or inappropriate exaggeration of mood. 5% of the population are depressed at any point in time. 30% of the population have had at least 1 episode of depression. 30,000 suicides in the USA per year are due to depression (9th leading cause of death).

Question 2

Major Depression: Genetics

Answer 2

Family studies:
Relatives of those with a mood disorder are two to three times more likely to have a mood disorder (usually major depression)
Twin studies:
If one identical twin has a mood disorder the other twin is 3 times more likely than a fraternal twin to have a mood disorder (particularly for bipolar disorder)
Severe mood disorders may have stronger genetic contribution than less severe disorders
Heritability rates are higher for females

Question 3

Evidence for monoamine hypothesis of depression in patients

Answer 3

There may be lowered levels of the 5-HT metabolite 5-HIAA in the cerebrospinal fluid (CSF) of depressed individuals (especially suicidal patients) (Asberg et al. 1976).

There may be lowered levels of dopamine metabolites (e.g. HVA) or norepinephrine metabolites (e.g. MOPEG) in the CSF of depressed individuals.

Question 4

Reserpine

Answer 4

Reserpine blocks the packaging of monoamines into vesicles

When neurons activated no transmitter released

Question 5

Tryptophan

Answer 5

Tryptophan depletion study (Delgado et al., 1990)
Tryptophan – precursor of 5-HT
amino acid normally available in the diet decrease in 5-HT
Symptoms of depression re-occurred
Once tryptophan was returned to the diet, the symptoms abated

Question 6

Monoamine Oxidase Inhibitors

Answer 6

MAO inhibitors: e.g. iproniazid (Crane, 1957) or phenelzine
Inhibit the breakdown of monoamines in the presynaptic terminal
Increase the proportion of monoamine that is taken up into the vesicles
Side effect: increased sympathetic tone & “Cheese effect”

Question 7

“Cheese Effect”

Answer 7

Cheese-type products contains tyramine which is normally deactivated by MAO in the liver. In the presence of MAO inhibitor tyramine is not broken down which results in the stimulation of the sympathetic system and an increase in heart rate and blood pressure.

Question 8

Reuptake inhibitors

Answer 8

Tricyclic antipressants: imipramine
Inhibit the reuptake of NA and 5-HT into the presynaptic terminal
Increase the length of time that NA and 5-HT are available in the synaptic cleft

Question 9

Depression and the Brain

Answer 9

Hippocampal atrophy in people with depression. They have a reduced volume.

Question 10

Stress hypothesis of depression

Answer 10

HPA axis

Hypothalamus releases CRH
Pituitary gland releases ACTH
Adrenal cortex releases cortisol
	(stress hormone)
     CRH: corticotrophin releasing hormone
  ACTH: adrenocorticotropic hormone

Cortisol – action at Glucocorticoid receptors (GRs) in hippocampus

In healthy people this axis is self-inhibited. In people with depression it does not self-regulate so they are just staying depressed.

Question 11

In situations of chronic stress how Ca is affected

Answer 11

Chronic activation of glucocorticoid receptors (GRs) in hippocampus
- increased Ca2+ entry into neurons
- too much Ca2+ - excitotoxic - cells die
Hippocampus can’t feedback to limit cortisol production
Can result in loss of feedback to the HPA axis and diminished hippocampal function.