Genetics of Psychiatric Illness

Question 0

What’s different about the nicotinic Ach receptor when people have the A allele of CHRNA5? Actual effect on the experience of nicotine?

Answer 0

It “fluxes” Ca++ less well…
It may be protective against the negative effects of nicotine… thus promoting use.
(but this allele confers very small increased risk……………)

Question 1

What’s one type of gene that predisposes people to nicotine addiction? Specifically?

Answer 1

Polymorphisms in nicotinic Ach receptor subunits.

A allele of CHRNA5, if it comes to that.

Question 2

What gene polymorphism can be protective against alcoholism by increasing the negative effects of EtOH?

Answer 2

Loss of function of acetaldehyde dehydrogenase, especially if homozygous.

Question 3

Polymorphisms in what gene may confer increased risk for alcoholism by increasing euphoria gotten from EtOH?

Answer 3

GABA-A receptor alpha 2 subunit gene. (aka GABRA2)

Question 4

What’s probably the most important reason that it’s so hard to find genetic causes of psychiatric diseases?

Answer 4

With the DSM criteria we’re almost definitely lumping together heterogenous diseases that have similar features.

Question 5

4 endophenotypes in SZ associated with cognitive deficits? How do you measure each?

Answer 5

Low activity in dorsolateral frontal cortex in cognitive tasks. (fMRI)
Enlarged lateral ventricles. (CT)
Delayed latency P300 evoked potentials (EEG) <- aka mismatch negativity?
Impaired gamma oscillations. (EEG)

Question 6

What’s P300?

Answer 6

Mismatch negativity (see the neurobiology of SZ lecture: hearing “the odd man out”)

Question 7

Polymorphisms in what gene related to SZ cause alterations in the P300 / mismatch negativity?

Answer 7

DISC1 (it causes P300 of decreased amplitude)

Question 8

Importance of copy-number variants in SZ?

Answer 8

Rare, but “strongly” correlated with recurrent psychosis and cognitive impairment….

Question 9

Gene associated with enlarged lateral ventricles in SZ?

Answer 9

MIR137

there’s a mnemonic involving space stations somewhere in there…

Question 10

Four genes found to be related to bipolar disorder in GWAS studies?

Answer 10

ANK3
SYNE1
CACNa1c
ODZ4
(I'm having trouble caring, too)

Question 11

What does ANK3 do?

Answer 11

Associated with V-gated Na channels to help them orient properly in the membrane.

Question 12

What’s CACNa1c?

Answer 12

L-type Ca++ channel alpha subunit….
associated with Timothy Syndrome, (autistic Sx + long QT)
and… apparently bipolar disorder
(and it illustrates that ion channels are important…. …)

Question 13

What’s an endophenotype that might be used for MDD?

Answer 13

Reduced hippocampus volume. (but no genes associated with this were mentioned…)