Epidemiology of major depressive disorder:
• 1 in ❌ primary care patients present with depressive symptoms.
• Lifetime risk of depression is 15% and 12 month prevalence is 4.1%.
• NZ - 17.9% of ❌ and 10.4% of ❌
• Highest rates in ❌ (21%)
• Mean age of onset is 27 years with 40% having a first episode by the age of 20
• 54% recover within 6 months, 70% within one year, 12–15% fail to recover and develop a chronic unremitting illness
• Economic cost in NZ > $2 billion/year

Match the symptoms/performances affected with their associated regions:
PFC, ❌ concentration, interest, pleasure, mental fatigue, guilt, worthlessness, suicidality, mood
S, striatum; ❌
NA, nucleus accumbens; ❌
HY, hypothalamus; ❌
A, amygdala; ❌
C, cerebellum; ❌

Diagnosis of depression requires ONE of: ❌.
Also requires at least ❌ of: appetite/weight change, sleep disturbances, cognitive ❌, agitation/restlessness, fatigue, suicidal ideation, worthlessness.

Major depressive disorder is the most ❌ mood disorder, defined by occurrence of at least a single major depressive episode - most people experience ❌ episodes.

Pathophysiology:
• Inefficient/dysfunctional ❌ projections to amygdala and VMPFC are linked to depression
• Poor information processing in the ❌ and NAc (NA, 5HT and DA projections) linked to psychomotor ❌/retardation
• ❌-active monoaminergic projections from the brain stem to the hypothalamus, basal forebrain and PFC linked to ❌ disturbances
• Feelings of guilt/worthlessness regulated by amygdala and VMPFC - inefficient or dysfunctional ❌ projections
• Suicidal ideation regulated by ❌ control of the amygdala, VMPFC and ❌ cortex (OFC)
• Weight and appetite 5-HT projections in the ❌

Monoamine receptor hypothesis of depression:
There is no clear convincing ❌ that monoamine deficiency accounts for depression – i.e., there is no “real” monoamine deficit, but increasing monoamines as a treatment is effective. The monoamine ❌ hypothesis of depression extends the classic monoamine hypothesis of depression, positing that ❌ activity of monoamine ❌ causes ❌regulation of ❌synaptic monoamine neurotransmitter ❌ which leads to depression.

SSRI mechanisms:
- Block 5-HT ❌ pump (❌)
- Increase ❌ (initially)
- Desensitize somatodendritic ❌
- Turn on ❌ and increase 5-HT ❌ from ❌ terminals
- Finally desensitize ❌ receptors

Mirtazepine - α2 ❌ - noradrenergic & specific serotonergic antidepressant (also blocks a couple ❌ receptors).
• α2-adrenergic receptors are mostly autoreceptors and heteroreceptors which enhance adrenergic and serotonergic neurotransmission. This:
a) stops ❌ turning off its own release (❌ feedback) so ❌ is increased
b) blocks ❌synaptic α2 ❌ i.e. the “brakes” on ❌ neurons, so there is enhanced ❌
• SEs - somnolence(excess ❌), sedation, ❌ mouth, weight ❌, increased ❌, ❌ and fatigue.

Agomelatine acts as a MT1 and MT2 receptor ❌ (involved in ❌) and 5HT(2C) antagonist.
- Stimulation of ❌ receptors helps ❌ depression-altered circadian rhythms, which potentially can optimize these changes in monoamines
- Binds to ❌ receptors on ❌ interneurons, prevents 5-HT from ❌ and prevents ❌ of NA and DA release in the ❌ cortex - ie facilitates their releases.

Venlafaxine (SNRI)
- Inhibits ❌ at low doses and also ❌ at increased doses
- Converted to active ❌, desvenlafaxine, by ❌2D6
- Desvenlafaxine also inhibits SERT and NAT but its ❌ effects are greater than venlafaxine - new drug...