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BB2 > Schizophrenia > Flashcards

Schizophrenia Flashcards

1
Q

Schizophrenia is a chronic mental disorder characterised by a triad of core symptoms. What are they?

A

Positive - hallucinations, delusions, agitation, disorganised thinking
Negative - introversion, apathy, low self-esteem leading to personal neglect
Cognitive - poor memory, attention deficit, executive dysfunction

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2
Q

What does alogia mean?

A

The inability to speak because of mental defect, mental confusion, or aphasia.

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3
Q

What does avolition mean?

A

A severe lack of initiative or motivation. A lack of interest to become engaged in goal-oriented behaviour.

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4
Q

According to the DSM-IV criteria, how long do symptoms have to be present for to make a diagnosis of schizophrenia? How many symptoms are needed?

A

Two or more of the symptoms, present for a significant portion of time during a 1-month period.

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5
Q

What symptoms are on the DSM-IV criteria? (5)

A

Delusions
Hallucinations
Disorganised speech
Grossly disorganised or catatonic behaviour
Negative symptoms (e.g. affective flattening, alogia, or avolition)

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6
Q

Identical twins – if one has schizophrenia, what is the lifetime risk of the other developing it? What about with fraternal twins?

A

48%

17%

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7
Q

What genes are associated with schizophrenia? Which has the most evidence and which has the least?

A
  1. Dysbindin (may affect dopamine D2 receptor levels and glutamate and GABA transmission) – strongest evidence in schizophrenia
  2. Neuregulin 1 (neuroplasticity)
  3. DISC 1 (neurodevelopment and signalling in corticolimbic areas)
  4. DAOA (glutamatergic transmission)
  5. and 6. COMT (dopaminergic transmission) and BDNF (neurotrophic factor) – weakest evidence in schizophrenia
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8
Q

There is a spectrum - prototypical schizophrenia, prototypical mood disorder, and schizoaffective disorder. Which susceptibility genes correlate to which one?

A

Dysbindin – prototypical schizophrenia
DAOA, BDNF – prototypical mood disorder
DISC 1, NRG1 – schizoaffective disorder

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9
Q

What is the classification of schizophrenia according to DSM-IV? (5)

A 
Paranoid
Disorganised
Catatonic
Undifferentiated
Residual
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10
Q

Cognitive dysfunction - why is it important in schizophrenia? How can it be tested?

A

It is an important predictor of outcome

Wisconsin Card Sorting Test

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11
Q

Is schizophrenia associated with structural changes in the brain?

A

Larger ventricles

Smaller mesial temporal lobe structures

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12
Q

What can be seen in PET scan imaging in schizophrenia?

A

Differences in regional blood flow - decrease

in pre-frontal cortex and increase in thalamus and cerebellum

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13
Q

A subset of patients with schizophrenia have brain loss. When is it more significant? What is it correlated with?

A

Frontal grey matter/brain loss is more significant in the first period of the disease. It is correlated with cognitive performance.

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14
Q

What is the Kraepelinian definition of poor outcome? What is this form of schizophrenia closer to?

A

Progressive deteriorating course

A form of neurodegeneration

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15
Q

What can be seen in Kraepelinian schizophrenia?

A

Prominent temporal sulcal markings and enlarged left temporal horn (temporal lobe volume loss and lateral ventricular enlargement).

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16
Q

When does schizophrenia start and why?

A

Schizophrenia is associated with decreased synaptic spines and decreased dendritic complexity in the cortex. At least some forms of schizophrenia are likely to be due to abnormalities in the formation and maturation of brain circuits.

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17
Q

Corticolimbic circuits - where are there excitatory connections?

A

Between…

  • Prefrontal cortex and temporal/parietal association cortices
  • Prefrontal cortex and anterior cingulate cortex
  • Prefrontal cortex and hippocampus and parahippocampal cortices
  • Prefrontal cortex and thalamus
  • Thalamus and anterior cingulate cortex

From…
- Prefrontal cortex to caudate/putamen

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18
Q

Corticolimbic circuits - where are there inhibitory connections?

A

From GP to thalamus and from caudate/putamen to GP

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19
Q

Corticolimbic circuits - where are there dopamine connections?

A

Ventral mesencephalon to…

  • Hippocampus and parahippocampus
  • Caudate/putamen
  • Prefrontal cortex
  • Anterior cingulate cortex
20
Q

What is the default mode network?

A

A network of brain regions that show synchronised activity when subjects rest and allow their minds to wander.

21
Q

How is brain connectivity altered in schizophrenia patients?

A

Altered brain connectivity of default brain network - the synchrony, which reflects the strength of functional connections between the different areas, is increased .

22
Q

Schizophrenia is associated with hyperactivity in which pathway? What about hypoactivity?

A

Mesolimbic pathway

Hypoactivity in the mesocortical pathway

23
Q

What are the major pharmacological target of drugs used to treat schizophrenia? What do these drugs act as?

A

Dopamine D2 receptors

Antagonists

24
Q

What are the two main families of dopamine receptors?

What sub-types belong to each family?

A

D1 type: D1, D5

D2 type: D2, D3, D4

25
Q

What is a neuroleptic drug also known as?

A

Antipsychotic

26
Q

What was the first antipsychotic drug?

A

Chlorpromazine (Largactil)

27
Q

Name some typical antipsychotics.

A 
Chlorpromazine
Thioridazine
Fluphenazine
Haloperidol
Flupenthixol
28
Q

Name some atypical antipsychotics.

A 
Risperidone
Olanzapine
Clozapine (blocks D4 receptors)
Quetiapine
Paliperidone
Aripiprazole (partial agonist)
29
Q

Is fluphenazine atypical or typical?

A

Typical

30
Q

Is clozapine atypical or typical?

A

Atypical

31
Q

Is paliperidone atypical or typical?

A

Atypical

32
Q

According to NICE guidelines, which type of antipsychotic is first choice? Which receptor do these all have antagonist activity at?

A

Atypical

5-HT2 receptors

33
Q

What is a major advantage of atypicals compared to typical antipsychotics?

A

They may improve cognition

34
Q

What explains the adverse effects of antipsychotics?

A

They have affinity for various receptors: D2, alpha 1 noradrenergic, 5-HT2, D1, histamine H1, muscarinic…

35
Q

Antipsychotics are associated extra-pyramidal effects - what do these include?
Is this more associated with typical or atypical?
How many % of D2 receptors have to be blocked for this to happen?

A

Acute dystonias, parkinsonism, tardive dyskinesia
Typical
80% (60% –> antipsychotic efficacy)

36
Q

List some side effects of typical antipsychotics.

A 
Rise in prolactin
Weight gain
EPS (e.g. tardive dyskinesia)
Cardiac toxicity (QT interval prolongation)
Sudden death
37
Q

List some side effects of atypical antipsychotics.

A

Weight gain
Dyslipidemia
Type 2 diabetes
Cardiovascular disease

38
Q

Which antidepressants are associated with anticholinergic effects?

A

Clozapine, haloperidol

39
Q

What is tardive dyskinesia?

A

Involuntary movements of the lips, jaw, face
Grimacing
Constant chewing
Tongue thrusting

40
Q

What is neuroleptic malignant syndrome?

A

A potentially lethal complication of antipsychotics. Symptoms/signs are:
Hyperpyrexia, muscle rigidity, tremor, confusion, autonomic instability.

41
Q

Some antipsychotics can be offered as depot intramuscular injections for slow-release - name two.

A

Fluphenazine and haloperidol

42
Q

How many % of schizophrenic patients do not respond to treatment

A

30%

43
Q

What is the drug of choice in drug resistant schizophrenia? Why must blood be monitered?

A

Clozapine

Risk of agranulocytosis

44
Q

What are the non-pharmacological treatments?

A

CBT and family Therapy

45
Q

Schizophrenia is associated with decreased glutamatergic transmission (hypoglutamatergic state in the cortex) - how could this be targeted for treatment?
Why is this beneficial over current antipsychotics?

A

It may be possible to potentiate the activity of the NMDA receptor in order to modulate glutamatergic transmission, to alleviate both positive and negative symptoms e.g. activate mGlu2/3 receptors.
No weight gain, increased prolactin or extra-pyramidal effects.

BB2 (32 decks)

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