L26 - Mood disorders

Question 1

How is depression defined?

Answer 1

1) Minimum of 5 symptoms on a sustained level:
1) Depressed mood
2) Diminished pleasure/interest in activities
3) Weight gain
4) Sleep disturbances
5) Psychomotor agitation or retardation
6) Fatigue
7) Feelings of worthlessness
8) Diminished concentration
9) Suicidality

2) Symptoms causes clinically significant distress in social, occupational, or other important areass of functioning
3) Symptoms not due to substance abuse or a general medical condition
4) Symptoms are not better accounted for by bereavement
5) Symptoms do not meet criteria for a mixed episode

Question 2

Are there any SNPs that can cause depression?

Answer 2

No

Question 3

Environmental factors that make you depressed are changes in the brain before or after birth?

Answer 3

Before

*Could be triple hit: genetics, environment pre birth, environment post birth

Question 4

People with arthritis have high rates of depression. People treating arthritis and the people had less or more depression symptoms? Why?

Answer 4

Less - Depression was brought about by cytokines in blood going into brain. Decreased inflammation = decreased cytokines = decreased depression

Question 5

Studies need to consider certain factors before determining cytokines from inflammation is a cause of depression. What factors?

Answer 5

Levels of inflammation-receptor proteins in blood vary with:

• sleep disturbance
• body weight
• glycaemic state
• diurnal variation
• sample storage conditions

Question 6

Altered expression in genes involved in inflammation and apoptosis in frontal cortex in major depression are? How about in BP disorder?

Answer 6

Changes in levels of mRNA for IL-1α, 2, 3, 5, 8, 9, 10, 12, 13, 15,18 as well as interferon γ and lymphotoxin αu.

BP - IL1 Beta

Question 7

What necrosis factor is increased in people with depression? And by how much?

Answer 7

TNF alpha - tumour necrosis factor alpha

Increase in TM TNF alpha and decrease in TNFR2.

As TM TNF binds to TNFR2, perhaps the system is downregulating amount of TNFR2 to prevent deleterious effects from occurring

Question 8

What necrosis factor is increased in people with BP disorder? And by how much?

Answer 8

TM TNF alpha increased and TNFR2 decreased

Question 9

What role does TNFR1 have? TNFR2?

Answer 9

TNFR1 = apoptosis or gliosis activation

TNFR2 has a role in cytoprotection

Question 10

What inactivates sTNF and TM TNF?

Answer 10

Monoclonal antibodies

Question 11

TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers. E.g. cytokines

Answer 11

TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers. E.g. cytokines

Question 12

People with depression had low/high levels of 5HTR2A receptor but low/high levels of TM TNF

Answer 12

Low, high

Question 13

People with depression have decreased/increased levels of muscR M2

Answer 13

decreased
*Interaction between TM TNF + M2 receptor= TNF R2 – in people with depression low TNF R2 and high TM TNF HENCE we think that the high TM TNF here is also leading to the decrease of M2

Question 14

Scopolamine

Answer 14

MuscR antagonist – used at the right dose, it can have long lasting rapid onset antidepressant effects, only works in a proportion of people resistant to classic anti-depressant treatments that don’t target Ach system in general