Depression and bipolar disorder

Question 1

Depression symptoms

Answer 1

For diagnosis with MDD, a patient must meet 5/9 symptoms and at least one of the first two:
Depressed mood
Loss of interest or pleasure
Change in weight or appetite
Insomnia or hypersomnia
Psychomotor retardation or agitation
Loss of energy or fatigue
Feelings of worthlessness or guilt
Impaired concentration or indecisiveness
Suicidal ideation or suicide attempt

Question 2

Monoamine hypothesis

Answer 2

Depression is due to a functional deficit of monoamine transmitters (5-HT, DA, NA), while mania is due to a functional excess.
Drugs that increase monoamine neurotransmission increase mood. Examples include:
TCAs that block reuptake, and MAOIs that inhibit metabolism.
Drugs that decrease monoamine neurotransmission decrease mood. Examples include reserpine, α-methyltyrosine and methyldopa that inhibit synthesis or storage.

Question 3

HPA axis in depression

Answer 3

Depressed patients express HPA hyperactivation.
There is increased plasma cortisol, but also increased CRH in the CSF and limbic brain regions → dysregulation, as cortisol release normally inhibits CRH release by negative feedback.
There is an increased size and activity of the pituitary and adrenal glands.
Antidepressants enhance negative feedback to decrease HPA axis hyperactivity.

Question 4

Neuroplasticity and neurogenesis

Answer 4

10% decrease in hippocampal volume in depression.
The hippocampus and subventricular zone of the lateral ventricles are the only regions capable of adult neurogenesis.
Neuroplasticity hypothesis - atrophy of mature neurons occurs. Dendrites are shortened and spine density decreases.
Neurogenesis hypothesis - decreased adult neurogenesis occurs, resulting in a decreased number of new neurons and neural precursors.
Both hypothesis are supported.
Ketamine, a rapid onset antidepressant, has no effect on monoamine signalling, but it increases the number and function of spines in the prefrontal cortex → neuroplasticity hypothesis
Many antidepressants increase adult neurogenesis
May involve BDNF

Question 5

Inflammation and depression

Answer 5

Depressed patients have an increased number of inflammatory markers.
Inflammation can precipitate depression.
Systemic diseases with an inflammatory component increase the risk of depression.

Question 6

Depression treatments

Answer 6

CBT aims to stop the negative cycle that influences emotion and behaviour.
MAOIs, such as phenelzine and tranylcypromine, inhibit monoamine metabolism. Can have food interactions → cheese reaction → reduced tyramine breakdown leading to hypertension.
SSRIs - citalopram, fluoxetine, sertraline, paroxetine
SNRIs - venlafaxine and duloxetine
TCAs - amitriptyline and imipramine → inhibit reuptake of 5-HT and NA, with some antagonism of H1 receptors and cholinergic signalling
Reboxetine - NA reuptake inhibitor.
Mirtazapine - antagonist at α2 and 5-HT2 autoreceptors → increases NA and 5-HT release

Question 7

Next generation depression treatments

Answer 7

Ketamine - NMDA antagonist → decreases hyperglutamatergic activity associated with depression.
Ketamine also affects mTOR and BDNF signalling → increases the number and function of neuronal spines in the prefrontal cortex.
Psychedelics - Psilocybin and COMP360 → 5-HT2A agonists
Vagal nerve stimulation may be used for treatment-resistant depression.

Question 8

What is bipolar disorder?

Answer 8

Bipolar disorder is a mental health condition that affects moods, which can swing from one extreme to another.
Involves episodes of depression and mania.
Mania symptoms include:
- inflated self esteem and grandiosity
- decreased need for sleep
- more talkative than usual or pressure to keep talking
- flight of ideas or racing thoughts
- distractibility
- increase in goal-directed activity
- excessive involvement in activities with potential for painful consequences
3/7 symptoms are required for diagnosis.

Question 9

Mania treatment

Answer 9

Lithium reduces excitatory dopamine and glutamate neurotransmission and increases inhibitory GABA neurotransmission. The therapeutic window is narrow so careful monitoring is required.
Antipsychotics, such as olanzapine, quetiapine, risperidone and cariprazine, reduce monoamine activity as they act as D2 and 5-HT2A antagonists.
Anticonvulsants such as valproate, carbamazepine and lamotrigine, reduce excessive electrical activity in the brain.