SZ - Basic Science Flashcards

1
Q

Which NIMH research domains is SZ studied under?

A

Cognitive impairment

Anhedonia

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2
Q

Which aspects of SZ can be modelled in rodents?

A
Locomotor changes
Psychomotor agitation 
Sensory gating abnormality 
Alteration in NTM levels 
Changes in cellular function
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3
Q

Describe the speech abnormalities in SZ

A

Word salad and knights move thinking
Perseveration
Rhyming

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4
Q

What abnormalities in action are seen in SZ?

A

Difficulty starting or finishing tasks
Bizarre behaviours with lack of purpose
Unpredictable emotional response

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5
Q

Describe frontal lobe activity in SZ?

A

Low

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6
Q

What is the DISC-1 mutation?

A

Translocation between chromosome 1 and 11 which truncates and activates the DISC-1 gene

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7
Q

What does the DISC-1 mutation put you at risk of?

A

SZ, bipolar and depression

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8
Q

What is the normal function of DISC-1?

A

Required for pyramidal cell migration

Tomita et al 2011

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9
Q

What is observed in DISC-1 KO mice?

A

Abnormal social behaviour
Reduced staining and abnormal interneuron activity

Pletnikov et al 2008

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10
Q

What does an inducible expression of DISC-1 in mice show?

A

Hyperactivity
Abnormal social behaviour
Ventricular enlargement
Reduced gamma synchrony

Pletnikov 2008

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11
Q

Give a brief outline of the neurodevelopmental hypothesis of SZ

A

There is hyperconnectivity between some neurons, and hypoconnectivity between others
Due to the aberrant neuronal migration (seen with the DISC-1 mutation)
This causes synaptic change

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12
Q

Outline the schizophrenia hypothesis of developmental oxidative stress

A

Oxidative stress damages cortical interneurons
Causing altered parvalbumin staining in the prodromal phase
This leads to E/Iimbalance
Then causing EEG alterations and cognitive defects

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13
Q

What is observed when monitoring rats with early hippocampal lesions?

A
Hyperactivity
Hypersensitivity to stress
Working memory deficits
Reduced PPI 
Reduced parvalbumin staining 
Developmental changes in DA 
Altered E/I balance
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14
Q

What are endophenotypes?

A

Simple, quantifiable and heritable biological or behavioural traits
Which segregates an illness

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15
Q

What do endophenotypes need to be?

A

Heritable
Stable across symptom state
Easily and rapidly measured
Reliable

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16
Q

What risk factor at age 15/16 can greatly contribute to SZ onset? How?

A

Cannabis consumption

Greatly decreases the density of glutamatergic synapses

17
Q

Where are the defects which lead to abnormal sensory gating?

A

Near the alpha 7 nicotinic receptor on chromosome 15

18
Q

What does the P50 wave abnormality on EEG mean?

A

SZ patients cannot filter out repetitive sensory stimuli

Clock ticking, etc

19
Q

Which other group of people is the P50 Wave defect seen in?

A

Relatives of SZ patients who don’t have SZ

20
Q

Which abnormal wave form in SZ in associated with “oddball detection”?

A

p300 wave

21
Q

What is pre-pulse inhibition?

A

When a prior stimuli gives a warning of a secondary event

There should be less of a startle response to the secondary event

22
Q

Describe PPI and startle inhibition in SZ

A

Both deficient

Unable to reduce the startle response

23
Q

Why do we think that dopamine is relevant to PPI?

A

Haloperidol is a d2 receptor antagonist
This reverses the PPI impairment in rodents
Implies too much dopamine is the cause

24
Q

Explain the dopamine hypothesis

A

Antipsychotics seem effective and they block d2 receptors
Elevated number of d2
receptors in SZ post-mortem
DA administration causes psychosis

25
Q

What evidence goes against dopamine being the only pathology in SZ?

A

DA altering drugs (ie haloperidol) can take minutes/hours to modify the DA levels
But weeks to become effective as antipsychotics

26
Q

Which other systems may be abnormal in SZ?

A

GABA and GLU

27
Q

Abnormalities in the mesolimbic system are responsible for which group of symptoms?

A

Positive

28
Q

Abnormalities in the PFC account for which group of symptoms?

A

Negative

29
Q

What evidence is there that cholinergic pathways are involved in SZ?

A

Treatment with alpha-7 agonists improves memory and attention
Defects in sensory gating are in the gene locus of the alpha 7 receptor
Post-mortem studies show reduced alpha 7 recs in the PFC
Increased smoking levels in SZ

30
Q

Outline the glutamate hypothesis in

A

GLU reduced in CSF in SZ

Mutations found in genes which code for GLU postsynaptic density proteins

Under-expression of GluN1 shows social isolation, motor problems and hyperactivity which is reversed by antipsychotics (Bear et al 2016)

31
Q

What evidence is there that NMDAR is involved in SZ?

A

Reduced NMDAR-mediated excitation of parvalbumin-positive interneurons
Ketamine also causes reduced staining (ket is an NMDAR antag) (Keilhoff et al 2004)

32
Q

Explain the GABA hypothesis of SZ

A

Reduced GABA synthesis and reuptake in parvalbumin positive interneurons

33
Q

What other environmental factors affect schizophrenia risk?

A

Intrauterine stress
Perinatal infection
City living

34
Q

What does mismatch negativity mean in terms of SZ?

A

SZ patients have no EEG pattern to suggest they are aware of an “odd one out” of a group
ie a tone with a higher pitch than others

35
Q

How does mismatch negativity error correlate to clinical disease?

A

There is more error (ie wave is less negative) with the symptom progression

(Control, at risk, recent onset, chronic)
(Rissling and Light 2010)

36
Q

Why is the pharmacological stimulant model of SZ not perfect?

A

Stimulant induced hyperactivity as this causes psychosis in humans
Antipsychotics suppres this
hyperactivity not specific to SZ thought (its seen in mania and ADHD)
And doesn’t develop, SZ is progressive like
Probs more info about drugs

37
Q

How can hyperactivity be measured in rodent models?

A

Open field activity

Intellicage