Major Depressive Disorders Flashcards
Two major forms:
MDD is depression characterized by…
Incidence of major depression is
Women have a 2 – 3 times…
Major depression
Bipolar disorder
severe reductions in mood
15 – 20%
higher risk
BD
Depressive phases are…
Manic phases are…
Bipolar I: Mania
Bipolar II: Hypomania – the manic phases are not as obvious and not as intense as in Bipolar I.
Cyclothymia: does not have manic phases, has hypomanic phases, also the depressive phases are not that intense
depressive phases are interspersed with period of elated mood (positive symptoms) - called manic phases
longer and more pronounced
shorter and less often occurring
Concordance rate in monozygotic twins is about…
60 – 70%
Potential Genetic Factors
- Serotonin
- Tryptophan Hydroxylase (synthesis of 5-HT)
- Serotonin Transporter
- 5-HT1A receptors
- Monoamine Oxidase A - Dopamine
- PCLO (involved in dopamine release)
- Dopamine transporter - Stress related proteins
- Corticotropin Releasing Hormone Receptors
- FKBP5 (involved in cortisol functioning)
Tryptophan Hydroxylase –enzyme that synthesizes serotonin mutations or genetic variations in those increased risk of developing major depressive disorder.
Monoamone Oxidase A – metabolizes serotonin, changes mutations/genetic variations linked to increased risk of developing depression
Genes related to serotonin, dopamine and stress-related proteins have been implicated in the etiology of depression.
The interaction between a genetic mutation in the serotonin transporter and stressful life events on the development of major depression.
impact of stressful life events (SLE) on the risk of developing depression was studied in individuals with a normally functioning serotonin transporter (LS or LL) and individuals with a serotonin transporter that was only functioning at about 50% of its normal capacity (SS).
early stressful life events enhanced the risk of developing depression especially in those individuals with a vulnerable genotype. The effect was seen both in males and females, more in females.
The regulation of cortisol:
Major player in regulating cortisol is the…
Part of the hypothalamus is the median eminence where BBB is weaker – hormones can go out.
CRH gets out of the hypothalamus in order to the reach the…
It stimulates the pituitary gland to release a hormone called…
ACTH gets into the blood and reaches the…
When the ACTH molecules in the blood reach the adrenal cortex, there are receptors there, that leads to the release of…
If there is a stressor the system gets activated, CRH is released reaches the pituitary gland that releases ACTH reaches the adrenal cortex, and releases cortisol (increases the blood pressure/heart rate – response to the stressor).
Cortisol inhibits it’s own release – negative feedback system.
If cortisol levels start to rise, after a while it will inhibit the hypothalamus leading to a reduction in the release of CRH and ACTH, decreasing the cortisol levels back to normal.
hypothalamus (hormonal regulation) pituitary gland ACTH adrenals (small glands on top of the kidneys) cortisol gives flight or fight ability.
The response to stress is regulated by the…
When a stressor activates our brain, the hypothalamus releases….
This neurohormone then stimulates the…
This hormone enters the bloodstream and releases…
This hormone then activates our body so that it can respond to the external stimulus that triggered it by stimulating specific cortisol receptors.
Since Cortisol receptors are also located in the hippocampus, the hypothalamus and the pituitary gland, cortisol also stimulates these receptors, leading to a reduction of…
Thus, cortisol regulates its own release via a…
hippocampus and the HPA-axis CRF adrenal cortex to release the hormone ACTH. cortisol from the adrenal glands. CRH and ACTH and ultimately cortisol. negative feedback mechanism.
Dexamethasone is a…
Dexamethasone inhibits release of ACTH from…
Dexamethasone induced suppression of cortisol is much less in…
direct cortisol agonist
the pituitary gland, resulting in lower cortisol in the blood.
patients with depression than in healthy controls, thus leading to chronically high levels of cortisol.
The effects of cortisol on the hippocampus Corticosteroids inhibit... Corticosteroids inhibit... Corticosteroids decrease... Corticosteroids decrease... Corticosteroids decrease...
neurogenesis - development of new cells
gliogenesis - development of new astrocytes, glia cells, microglia and oligodendrocytes)
dendritic branching - influence out-growth of dendritic branches in neurons
spine formation
concentration of BDNF
The effects of cortisol on the hippocampus
Dendritic spines are small protrusions on dendrites where…
Increase in stress hormones leads to a reduction in spines and further reduction in….
BDNF is involved in increasing…
Cortisol can inhibit the production of BDNF, suggesting that the reduction in spines is due to…
Patients with MDD have chronically lowered…
the dendrites receive synaptic input from other cells
synaptic communication
spine formation
lack of BDNF
plasma levels of BDNF
The effects of cortisol on the hippocampus
Dendritic spines are small protrusions on dendrites where…
Increase in stress hormones leads to a reduction in spines and further reduction in….
BDNF is involved in increasing…
Cortisol can inhibit the production of BDNF, suggesting that the reduction in spines is due to…
Patients with MDD have chronically lowered…
During depression, high levels of cortisol inhibit the effects of…
After high levels of cortisol, decrease in…
As a result reduction in…
A reduction in the number of…
the dendrites receive synaptic input from other cells
synaptic communication
spine formation
lack of BDNF
plasma levels of BDNF
BDNF and therefore reduce plasticity, such as spine formation
BDNF
outgrowth of spines (less branching of the dendrites)
spines - a lack of communication between brain regions and the hippocampus.
The monoamine hypothesis of antidepressants (1) Reserpine: Used as an... Induced severe signs of... Rapidly decreases... Inhibits uptake of....
antihypertensive drug
depression
high blood pressure
NT in vesicles, especially monoamines
The monoamine hypothesis of antidepressants (1) Reserpine: Blocks... Decreases... Increases...
Blocking the transport of monoamines into these vesicles, reducing the release of NT when an AP arrives at the terminal region leads to depressive symptoms.
Irreversible inhibitor of the transporter that takes up monoamines into the vesicles of the presynaptic terminal (different transporter than the re-uptake transporter that takes up extracellular NT into the presynaptic terminal)
uptake of NT in vesicles
monoamines
depression
The monoamine hypothesis of antidepressants
(2) Iproniazid:
Used in the treatment of…
Appeared to have…
Blocks…
Increases…
Indirect monoamine agonist
Decreases…
tuberculosis
antidepressants action
MAO (enzyme that breaks down monoamines)
Monoamines
Block the breakdown of NT, increase the actions of NT.
Depression
Monoamineoxidase
- Localised on the…
- Two forms:
mitochondrial wall
MAOA: metabolism of NE and 5-HT
MAOB: metabolism of DA
