Depression and Mania

Question 1

Depression was thought to be a build up of what in the olden days ?
what was the treatment ?

Answer 1

build up of black bile

blood letting / purging

Question 2

a country with one of the highest antidepressant use is ?

Answer 2

iceland

Question 3

brief episodes of severe depression are referred to as

Answer 3

brief recurrent depression

Question 4

More prolonged recurrence of depression is referred to as ?

Answer 4

recurrent depressive disorder

Question 5

what percentage of patients are resistant to treatment ?

Answer 5

20-30%

Question 6

what is Dysthmia ?

Answer 6

persistent mild depression

Question 7

Is Dysthmia and MDD more common in males or females ?

Answer 7

females

Question 8

Brain area believed to be involved in depression ?

Answer 8

Orbital prefrontal cortex and the ventromedial prefrontal cortex
Dorsolateral prefrontal cortex
Hippocampus and amygdala
Anterior cingulate cortex

Question 9

what happens to the HPA axis in depressed patients ?

Answer 9

its upregulated with downregulation of negative feedback mechanisms

Question 10

upregulation of HPA axis leads to ….

Answer 10

Hypersecretion of CRF induces increased ACTH release from the pituitary.

Leads to increased cortisol release and also adrenal hypertrophy.

Impaired negative feedback -> the system can’t shut down -> continual release.

Cortisol receptors become desensitized leading to increased activity of pro-inflammatory mediators and disturbances in neurotransmission.

Increased activation can lead to hippocampal atrophy.

Question 11

How does depression affect neurogenesis ?

Answer 11

decrease in BDNF
dendritic spines
and synaptic connections

Question 12

what happens to the Hippo C in depression ?

Answer 12

it shrinks

Question 13

A theory as to why anti-depressant medication takes weeks to have an effect ?

Answer 13

Antidepressants may stimulate neurogenesis which takes weeks thus there effects aren’t felt until longterm use

Question 14

what neurotransmitters do the current antidepressants target ?

Answer 14

monoamines

Question 15

Examples of TCA and SSRIs what do they target ?

Answer 15

TCA - imipramine
SSRI - fluoxetine

inhibt action of SERT at synaptic cleft - less uptake of 5HT

Question 16

How do MAOIs work ?

Answer 16

prevent breakdown of monoamines

Question 17

how long does it take for antidepressants to take effect ?

Answer 17

4-6 wks

Question 18

Unwanted side-effects of SSRIs include?

Answer 18

nausea, fatigue, reduced libido, insomnia.

Question 19

transferring the microbiota of a depressed rat into a germ free rat causes ?

Answer 19

the germ free rat to exhibit depressive symptoms

probiotics can improve depressive symptoms

Question 20

what diet has benn shown to improve depressive scores ?

Answer 20

Mediterranean diet

Question 21

Why was ketamine thought to be a good antidepressant ?

Answer 21

rapid antidepressant effect that lasts for 2 weeks

Question 22

why wont ketamine be used as a longterm treatment ?

Answer 22

its a Dissociative anesthetic. Less efficacy after first dose.
Only approved for patients with treatment resistant depression when an immediate intervention is needed.

Question 23

How does ketamine bring about its antidepressant effects ?

Answer 23

inhibits NMDA receptors leads to activation of AMPA and downstream signalling of mTOR - synapse formation

Question 24

What is bipolar disorder ?

Answer 24

episodes of depression and mania occur across lifespan. Between these episodes patients are often symptom free.

Question 25

Two types of biopolar disorder?

Answer 25

Bipolar I disorder: which involves recurrent episodes of mania and depression Bipolar II disorder: Some people, however, never develop severe mania but instead experience milder episodes of hypomania that alternate with depression;

Question 26

Rapid cycling betwee episodes of mania and depression occurs more commonly in which sex ?

Answer 26

females

Question 27

Switching from a depressive to a manic state can occur spontaneously, but can also be influenced by exposure to ?

Answer 27

stress, sleep deprivation or illict drugs

Question 28

what have been known to induce switching ?

Answer 28

ECT, antipsychotics and some antidepressant therapies can induce switching

Question 29

what is the underlying neurobiology of bipolar disorder ?

Answer 29

``` Dysfunctional neurotransmission (↑NA, ↓5-HT, ↑ DA) GABA/glutamate imbalance ``` HPA-axis dysfunction - Bipolar patients more vulnerable to cycling when treated with GCs. - Failure to regulate cortisol release -> hypercortisolemia Disrupted intracellular signaling pathways (e.g GSK3β, role of calcium) Redox dysregulation Neuroinflammation

Question 30

what is lithium ?

Answer 30

a mood stabiliser for treatment of mania, is often very effective in controlling mania and preventing the recurrence of both manic and depressive episodes (prophylaxis)

Question 31

side-effects of lithium ?

Answer 31

``` Narrow therapeutic index Long duration of action Toxicity includes Cerebellar effects, Nephrogenic diabetes insipidus Renal failure Thyroid problems and cognitive effects (chronic use) Dose must be adjusted according to [plasma] Diuretics can increase toxicity ```

Question 32

Mechanism of action of lithium ?

Answer 32

readjusts balances between excitatory and inhibitory activities, and decreased glutamatergic activity and may contribute to neuroprotection Inhibition of hydrolysis of myoinositol phosphate reducing level of free myoinositol for synthesis of phophatidylinositides. PIs involved in intracellular calcium regulation modulates signals impacting on the cytoskeleton, a dynamic system contributing to neural plasticity, at multiple levels, including glycogen synthase kinase-3 , cyclic AMP-dependent kinase, and protein kinase C, which may be critical for the neural plasticity involved in mood recovery and stabilization. Inhibition of glyogen synthase kinase Inhibition of phospholipase C signalling

Question 33

Examples of other mood stabilisers ?

Answer 33

Anticonvulsant medications, such as valproate or carbamazepine, also can have mood-stabilizing effects and may be especially useful for difficult-to-treat bipolar episodes

Question 34

Possible biomarkers for depression ?

Answer 34

Abnormal CV function Sexual dysfunction Changes in brain morphology Functional GI disturbances