MENTAL HEALTH I - GxE studies/Stress

Question 1

Common mental health disorders that are having large burden on global disease?

Answer 1

-Depression -anxiety -bipolar disorder - addiction -schizphorenia

Question 2

What is the % burden on global disease and why is mental health such a big problem?

Answer 2

• Patients face systematic discrimination

- 10% of global disease burden

Question 3

What is ‘mental health’?

Answer 3

Refers to factors which influence the health of the mind, brain and CNS/PNS

Question 4

What are the advantages of GWAS?

What were used before this?

Answer 4

Can identify genes that correlate with the emergence of a disorder
Before this, risk factors were identified in inbred families

Question 5

DISC1 - what was shown re DISC1 in schizophrenic patients?

How was this identified?

Answer 5

• DISC1 was identified as being disrupted in Schizophrenia therefore seen as a genetic risk factor of mental illness
• This was identified through genetic analysis of INBRED FAMILY

Question 6

Why are genetic factors not the full story in mental illness?

Answer 6

Other factors can act as triggers too - - social and environmental factors act as TRIGGERS such as

• lack of sleep
• stress
• substance abuse

Question 7

Common model used in study of mental health, why are these models used?

Answer 7

-Zebrafish
-Fly
These models have a short generation time and a lot of them can be observed at once - because mental health is so poorly understood this is a great advantage because it means that more robust conclusions can be made

Question 8

What was shown re DISC1 and the zebrafish hypothalamus?

Answer 8

DISC1 was shown to be expressed in the developing hypothalamus and hypothalamic stem cells

Question 9

WHat is the hypothalamus and why is it important?

What are some of the relevant populations of neurons in the hypothalamus important for?

Answer 9

Hypothalamus is the central regulator of the brain and is a highly conserved ancient structure.
Has diff popultions of neurons involved in the STRESS PATHWAY

Question 10

What are the roles of the different populations of neurons found in the hypothalamus?

Answer 10

• SF1 - helps to form active hormones
• Crh - releases corticotropin hormone (which will eventually become cortisol)
• Pomc - produce Pomc which is a precursor protein that produces ACTH

Question 11

DISC1 fish - what was seen upon the production of 2 transgenic lines of zebrafish with point mutations whereby DISC1 mRNA (therefore protein) production didn’t happen?

Answer 11

• Mutants make fewer Pomc neurons and Crh/SF1 neurons too quickly
• The neurons differentiate too quickly so LESS HYPOTHALAMIC STEM CELLS are seen
• Abnormal number (less) progenitor cells

Question 12

How is stress response measured in model organisms?

Answer 12

• BEHAVIOURAL ASSAYS

- NEUROENDOCRINE FUNCTION (are certain hormones such as cortisol upregulated after stress?)

Question 13

What was the DISC1 response showed by mutants?

Answer 13

SHowed an abnormal stress response – didn’t respond to stress stimulation!

Question 14

What are the 2 ways you can stress zebrafish?

Answer 14

• Add NaCl to solution they are in

- Add a bit of dead zebrafish

Question 15

Outline the events that occur along the biological stress axis?

Answer 15

Organism is presented with a stress stimulus
-ACTH is released from the pituitary gland and binds to the adrenal gland, causing release of cortisol. Cortisol is released into the bloodstream and impacts cells to coordinate the stress response