mental health 1

Question 1

why is there an increasing need in investigating mental health?

Answer 1

• 10% of disease burden
• are few resources worldwide to fund necessary research - treatment gaps are large and there is unmet care and support
• leading cause of disability worldwide

Question 2

give some exmaples of neuropsyciatric disorders

Answer 2

depression
anxiety
mental health of childhood
eatng disorders
schizophrenia
bipolar
alcohol and drug abuse

Question 3

what is DISC1?

Answer 3

disrupted in schizophrenia?

Question 4

how was DISC1 discovered?

Answer 4

-discovered in an inbred family who had high risk of mental problems
(DISC1 was mutated in inbred family)

Question 5

what social and environmental factors can act as triggers for neuropsyciatric disorders?

Answer 5

shows is genexenvironment interactions

- stress, substance abuse, lack of sleep

Question 6

why is it hard to understand the cause of mental health conditions?

Answer 6

• is much variation - gene x environment
• many variables - hard to dissect mechanism
• important to analyse high numbers so a robust conclusion can be made (zebrafish and drosophila useful for this)

Question 7

what areas are involved in the stress pathway?

Answer 7

• hypothalamus
• pituitory gland
• interrenalgland/adrenal gland (release cortisol)
• is negative feedback loops

Question 8

why is negative feedback important in the stress pathway?

Answer 8

the stress pathway cannot be maintained so negative feedback loopsstops the release of cortisol

Question 9

what was shown by zebrafish DISC1 mutants?

Answer 9

• hypothalamic progenitors develop abnormally (differentiate prematurely)
• hypothalamic neurons differentiate abnormally (fewer pomc neurons, more sf1 and crh neurons)
• fail to upregulate cortisol levels
• stress response is abnormal

Question 10

how was stress response analysed in zebrafish DISC1 mutants?

Answer 10

• addition of NaCl or Schreckstoff should cause a stress response in fish - swim faster and change direction lots
• in DISC1 mutants fish did not show stress response when these were added to tank - abnormal stress ehaviour

Question 11

what is upregulated in WT zebrafish which is not upregulated in DISC1 mutant siblings?

Answer 11

• in WT fish ff1b and cotisol is upregulated when stressed but this does not occur in DISC1 mutant fish (no upregulation of stress hormones)
• mutants cannot upregulate cortisol levels in response to stress (altered crh nlevels?)

Question 12

what is DISC1 essential for?

Answer 12

DISC1 is essential for the normal development ofthe hypthalamus and for the correct function of the HPI/HPA axis (stress pathway)
- has a role in the stress response - evolutionary conserved

Question 13

what happens to hypothalamic progenitors in 2 stains of DISC1 mutant zebrafish?

Answer 13

• proliferating rx3+ hypothalamic progenitors are not maintained properly and neuronal differentiation is compromised - premature?
• rx3 and pomc neurons are disorganised

Question 14

WHat does a GWAS do?

Answer 14

investigates the entire genome of a population of individuals e.g. dieased and on-diseased

• identifies SNPs and DNA variations which associate with disease- increasing suseptibility
• seen on manhatten plot - SNPs plotted

Question 15

what is a sNP?

Answer 15

single nucleotide polymorphism

• variation at a single site in DNA
• identified using SNP arrays