Case 6 - Depression Pathophysiology

Question 1

what is major depression defined by

Answer 1

the DSM-V criteria.

Question 2

epidemiology of depression

Answer 2

10-16% of men and 20-24% of women will have some symptoms of depression

2-4% of men and 7-8% of women will have actual depression at any given time

Question 3

what is the most common GP diagnosis

Answer 3

depression and it is present in 17% of people who present to GP in any given year

Question 4

what is the mean onset age of depression

Answer 4

27

Question 5

how many depressed patients also suffer from anxiety

Answer 5

50%

Question 6

what are the differentials for depression

Answer 6

hypothyroidism
bipolar disorder
cancer or terminal diagnosis

Question 7

what is the DMS-V diagnostic criteria

Answer 7

diagnosing depression requires a relative short history of at least 2 weeks

Question 8

what is the actual criteria

Answer 8

at least five of the following almost every day for the last 2 weeks. number ONE and TWO are essential

• depressed mood
• loss of interest or pleasure in previously enjoyed activites
• changes in weight or change in appetite
• change in sleep - insomnia or hypersonmia
• psychomotor agitation or retardation
• fatigue or low energy
• feelings of worthlessness of guilt
• reduced concentration or decisiveness
• suicidal attempt or ideation

Question 9

what else must you have to fit the criteria

Answer 9

symptoms cause significant distress or impair functioning
- symptoms not due to a medication, or other substance
- symtoms are not better explained by a schizophrenia spectrum disorder or psychotic disorder
- no history of a manic or hyper main episode

Question 10

what are the three core symptoms

Answer 10

low mood
anhedonia: does not take measure from any activities patients will often withdraw from social activities
low energy levels

Question 11

what is a significant weight gain

Answer 11

5%

Question 12

what may be present

Answer 12

hallucinations and delusions

Schneider’s positive symptoms can occur In severe depression

Question 13

what is melancholia

Answer 13

this is where the patient feels unable to experience any emotions at all - emotional numbers

Question 14

what are the screening tools used

Answer 14

hospital anxiety and depression score (HADS) - despite its name is still used in general practice
Patient health questionnaire (PHG-9)
ICD-10 depression inventory (MDI)
DASS 21 or DASS 42
Also include assessment of anxiety and stress

Question 15

what is psychotherapy

Answer 15

the process of explaining the diagnosis and its effects

Question 16

what is CBT

Answer 16

a type of talking therapy which helps the patient to better understand their symptoms and helps them to recognise negative thought patterns, and how better to manage these thoughts, including teaching new ways of positive thinking

Question 17

why should u be careful of using anti depressants in bi polar disorder

Answer 17

anti depressants can worsen bipolar disorder, and these patients are instead treated with mood stabilisers (lithium)

Question 18

what is the aim of treatment

Answer 18

to induce remission

Question 19

what is the first line treatment for depression

Answer 19

ssri’S

Question 20

What are some examples of SSRI’s

Answer 20

fluoxetine, citalopram, sertraline, paroxetine

Question 21

how long should you allow for beneficial effects

Answer 21

4-6 weeks

Question 22

what are SSNRI’s

Answer 22

serotonin-noradrenaline re uptake inhibitors e.g venlafaxine. may be superior t SSRI in severe depression

Question 23

what happens if medication is successful

Answer 23

if medication is successful and remission is achieved, it is recommended to continue medication for at least 12 months

if there are further episodes = continue treatment for 2-3 years when it is restarted

Question 24

drug mechanism table

Answer 24

Question 25

what is the typical regimen for ECTq

Answer 25

1-3 sessions per weeks for 8-12 weeks

Question 26

what is the mechanism of ECT

Answer 26

It is thought that is induces grand mal type seizures and that there are necessary for antidepressant effect. it is also thought that seizures that originate in the lower brain areas are less effective that seizures that originate higher in the brain stem at reducing depression

using a high electrical current increases the therapeutic effect, but can incerease the risk of memory loss and conduction

Question 27

more on ECT

Answer 27

uilateral treatment to the non-dominant hemisphere also reduces the risk of confusion and memory loss, but again has reduced efficacy. patients who undergo this type of ECT require 2-4 more sessions than other individuals

ECT increases the acuity of 5-HT in the cell and increases the number of post synaptic 5-HT receptors. it also enhances dopamine activity and has similar effects on noradrenaline to anti depressant drugs

Question 28

what are patients given during ECT to reduce the risk of injury

Answer 28

a muscle relaxant

Question 29

what are they given to reduce bradycardia

Answer 29

atropine to reduce salivary and bronchial secretion and prevent bradycardia

Question 30

what are patients given before treatment begins

Answer 30

ventilated with 100% O2 which Is proven to reduce amnesia

Question 31

where are the electrodes placed

Answer 31

uni lateral - one on temporal region, one near vertex
bilateral - on each temporal region

Question 32

how long should depression treatment be continued for

Answer 32

minimum of 9 months otherwise there is a 80% risk of relapse

Question 33

what are factors that point to a good outcome

Answer 33

large loss event precipitating the depression
normal pre-morbid personality

Question 34

what is the mitochondrial dropout theory of depression

Answer 34

increased glucocorticoids in response to stress leads to excessive mitochondrial and subsequent neuronal death

Question 35

what glional death

Answer 35

brain derived neurotrophic factor (BDNF) is a protein in the brain that protects neurones from damage
the neurotransmitter serotonin, noradrenaline, and to a lesser extent dopamine, all cause increased synthesis of BDNF

the end result of these factors is decreased brain activity in the prefrontal cortex, and increased activity in the limbic system
microscopically, the brains of those with chronic depression can be seen to have neuronal cell death.
macroscopically on MRI there may be seen up to 1/3 reduction inside of the hippocampus

Question 36

what is the mopoaimine theory

Answer 36

it states that depression results of under activity of mopoaimine transmitters, and conversely that mania results from overactivity of monoamine transmitters

Question 37

what is main transmitter I the monoamine theory

Answer 37

serotonin

Question 38

where to most serotonergic neurones arise

Answer 38

in the Raphe area of the midbrain, and project to the limbic system and cerebral cortex

Question 39

where are most noradrenaline neurones found

Answer 39

in the locus cereleus and lateral tegumental areas of the brain steam

Question 40

where does the evidence for this theory come from

Answer 40

there are reduced levels of 5-HT in the brains of depressed people
- there are increased numbers of 5-HT receptors in the brains of suicidal patients

Question 41

what is the hypothalamic involvement in depression

Answer 41

hypothalamic neurones relieve 5-HT input, which alters their output. in turn, they release CRH which controls ACTH and ultimately steroid levels. in depressed patients, cortisol levels are usually high because the hypothalamic neurones are not suppressed as much as normal,

Question 42

what happens when there is excess CRH

Answer 42

actually causes some of the symptoms of depression, such as anxiety, reduced activity etc and CRH level are also usually raised in depression

Question 43

what about neuroplasiticty and hypotrophy in depression

Answer 43

in depressed patients, there is often neurone loss in the hippocampus and prefrontal cortex. also many of the theories used to treat depression, and thus ultimately 5-HT itself actually promotes neurogenesis