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Module 202 Theme 3 > Schizophrenia: Neurobiology and treatment > Flashcards

Schizophrenia: Neurobiology and treatment Flashcards

1
Q

Describe how genes cause schizophrenia

A

Genetic Risk:
1% general population up to ~50% risk in monozygotic twin

Partial penetrance

Likely to be polygenic multiple susceptibility genes

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2
Q

What is partial penetrance?

A

Interaction of the genes and environment

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3
Q

What do the genetics of schizophrenia overlap with?

A

Genetics of autism and other neurodevelopmental disorders

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4
Q

What is the peak age of onset for males?

A

20-28

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5
Q

What is the peak age of onset for females?

A

26-32

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6
Q

List some environmental events which may give rise to schizophrenia

A 
Obstetric complications - prenatal infection, nutritional deficiency 
Adverse life effects
Substance abuse (cannabis use 6X risk)
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7
Q

Describe some structural changes of schizophrenia

A

Ventricular enlargement
Reduced brain volume (less gray matter - temporal lobes, frontal lobes, subcortical structures)
Cytoarchitectural differences in cortex and hippocampus

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8
Q

Which structure in the brain is associated with hallucinations?

A

Paracingulate sulcus

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9
Q

What is the paracingulate sulcus used in?

A

Reality monitoring

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10
Q

Describe the neurodevelopmental model of schizophrenia

A

During adolescence grey matter is lost, if this happens excessively then this may cause early-onset schizophrenia

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11
Q

Describe the wisconsin card soring task

A

You are told to match the sample, but not how to match it (what the rule of matching is in the current trial). Sensitive to executive dysfunction, set-shifting, cognitive flexibility etc.

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12
Q

Describe the neurophysiology of schizophrenia

A

Hypofrontality

Hyper-excitable sensory cortex

Abnormal neural oscillations

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13
Q

What is pruning?

A

Pruning is a sort of clean-up job conventionally thought to eliminate weak synapses and leave strong ones.
Occurs in adolescence

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14
Q

Describe hypofrontality

A

Increases on activity in dIPFC seen in healthy volunteers absent in schizophrenics
Correlate with negative and cognitive symptoms

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15
Q

Describe the fMRI evidence of auditory cortex activation during hallucinations

A

Patients press a button during
auditory verbal hallucinations –
Correlation with BOLD signal

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16
Q

What are oscillations?

A

important organizers of brain activity, plasticity and connectivity (*maturation)

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17
Q

What is meant by neuronal synchrony?

A

well-timed coordination and communication between neural populations

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18
Q

What happens to the oscillations during schizophrenia?

A

High frequency oscillations and synchrony emerge during the transition from adolescence to adulthood.

Differences in neural oscillations and synchrony between controls and patients with schizophrenia.

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19
Q

How are dopamine neurons arranged in the brain?

A

Cell bodies in the midbrain which project to the forebrain

20
Q

What are the components of the dopaminergic system?

A

Nigrostriatal system -
Mesolimbic system
Mesocortical system

21
Q

What is the gamma rhythm used for?

A

Attention
Perception
Working memory

22
Q

What is the mesocorticolimbic system used for?

A

Reward and reinforcement, provides stimulus salience

23
Q

What was the first antipsychotic drug?

A

Chlorpromazine

24
Q

What is haloperidol?

A

More potent than chlorpromazine

25
Q

Which drugs are given to prevent positive symptoms?

A

Typical antipsychotic (nuroleptic) drugs

26
Q

What are typical antipsychotics?

A

D2 receptor antagonists

27
Q

What are the side effects of typical antipsychotics?

A

Parkinsonian-like side effects:

Antipsychotic dosage correlates with their potency as D2 receptor antagonists

28
Q

Give some examples of dopamine agonists

A

cocaine, amphetamine, L-DOPA

29
Q

What can dopamine agonists do?

A

cause positive symptoms of schizophrenia (e.g. psychosis)

30
Q

How are drug induced psychosis treated?

A

treated with the D2 antagonist antipsychotic drugs.

31
Q

Which G protein is the DR receptor coupled to?

A

Gi

32
Q

What are atypical antipsychotics?

A

Atypical antipsychotics can work in patients resistant to typicals
Atypicals do not have same extra-pyramidal side effects (lower activity at D2 receptor)

33
Q

What is the main atypical antipsychotic?

A

Clozapine

34
Q

Where does clozapine act?

A

activity mainly at D4 receptors (also binds D3, D1, D2, D5)
5HT receptors
improves positive and negative symptoms

35
Q

Give the side effects of clozapine

A

weight gain, sedation, hypersalivation, tachycardia, hypotension, neutropenia (needs to be watched - blood tests)

36
Q

List some other atypical antipsychotics

A

Risperidone, Olanzapine - differing affinities for receptor subtypes, varying levels of side effects.

37
Q

Give evidence of the glutamate hypothesis in schizophrenia?

A

PCP Causes many positive, negative and cognitive symptoms of schizophrenia
NMDA receptor antagonist

Genetically engineered mice with
fewer NMDA receptors.

38
Q

Describe PCP treatment results in animal studies

A

NMDA antagonism in PFC - less glutamatergic firing to VTA GABA neurons
Less GABAergic inhibition of VTA-NAcc DA neurons
Greater DA release in NAcc
Less activation of VTA-PFC DA neurons - less Glu - hypofrontality

39
Q

What are dopamine agonists?

A

Causes psychosis

40
Q

What are dopamine antagonists?

A

Antipsychotic

41
Q

Where do dopamine agonists and antagonists act?

A

Nucleus accumbens

42
Q

What do atypical antipsychotic drugs do?

A

Increase DA activity in PFC
and
Decrease DA in NAcc

43
Q

How do the different drugs affect the enduring symptoms of the disease?

A

typical antipsychotics - no effect on these symptoms

atypicals - some improvement, e.g. increase verbal fluency

44
Q

List the neurocognitive deficits of schizophrenia

A 
Lower IQ
Attentional deficits (e.g. Stroop Test)
Working memory (e.g. Wisconsin Card Sorting Test)
Planning and information processing deficits
45
Q

How do schizophrenia patients perform on the stroop test?

A

Patients with schizophrenia are slower and less accurate (hard time inhibiting the other contextual information and attending to the colours)

Module 202 Theme 3 (11 decks)

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