Mer Scott
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PHCY320 (Psychiatry) Quiz on PSY7 Schizophrenia, created by Mer Scott on 13/10/2019.

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PSY7 Schizophrenia

Question 1 of 23

1

Which of these is not a disorder in which psychosis is defined?

Select one of the following:

  • Psychotic disorder due to a general medical condition

  • Substance-induced psychotic disorder

  • Schizophrenia

  • Schizoaffective disorder

  • Delusional disorder

  • Bipolar

Explanation

Question 2 of 23

1

Schizophrenia:
~ % of population, psychotic illness, mostly people, (regular/irregular psychotic episodes), lifelong and highly disabling.

Positive and negative symptoms:
- A positive symptom is one that a behavior, thought or feeling. Positive symptoms associated with schizophrenia also occur in other disorders such as , psychotic depression, and 's. Positive symptoms are – (paranoid), hallucinations, thought , other abnormal behaviors e.g. aggression.
- Negative symptoms a behavior, thought or feeling. Negative symptoms – flattened response, social , apathy, anhedonia.

Cognitive symptoms:
- - poor methodical planning in brain makes basic tasks difficult
- Difficulty representing and maintaining , allocating , evaluating/monitoring performance
- Impaired fluency
These are the best predictor of outcome.

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    1
    young
    chronic
    adds
    bipolar
    Alzheimer
    delusions
    disordered
    take away
    emotional
    withdrawal
    Executive dysfunction
    goals
    attention
    verbal

Explanation

Question 3 of 23

1

Burden of illness
• 25-50% attempt suicide and % eventually succeed
• Mortality rate 8 times higher than general population due to high rate of etc,
• Life expectancy years shorter than the general population
• Patients - early onset, intellectual , relationships, risk of suicide, stigma, self treatment:
• Family/Care Giver - stressors, financial , pressure on
• Community – healthcare, economic, stigma
• Duration of (DUP) has major impact on outcomes

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    10
    CV disease, suicide
    25-30
    development
    drugs, alcohol and smoking
    cost
    relationships
    untreated psychosis

Explanation

Question 4 of 23

1

Early symptoms indicating the onset of schizophrenia:
• Worrisome drop in
• New trouble
• Suspiciousness, ideas or uneasiness with others
• Withdrawing socially, spending a lot more time than usual
• Unusual, overly intense new , strange feelings or having feelings at all
• Decline in
• Difficulty telling reality from fantasy
• Confused or trouble communicating

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    grades or job performance
    thinking clearly or concentrating
    paranoid
    alone
    no
    ideas
    self-care or personal hygiene
    speech

Explanation

Question 5 of 23

1

Match the symptoms to the region:
Positive symptoms -
Affective symptoms (anxiety, suicidality) -
Aggressive symptoms -
Cognitive symptoms -
Negative symptoms -

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    mesolimbic pathway
    ventromedial prefrontal cortex
    orbitofrontal cortex, amygdala
    dorsolateral prefrontal cortex
    mesocortical pathway, prefrontal cortex

Explanation

Question 6 of 23

1

Diagnosis
• Based on patient and often family following presentation of first psychotic episode
• Clinical status/rating determined using psychiatric examination with (PANSS) and Clinical Global Impression scales (CGI) - commonly use Diagnostics and Statistics Manual (DSM-V) or ICD-11
• Also use At Risk Mental State (ARMS) Brief Psychiatric Scale (BPS)
not otherwise specified often in patient notes due to associated with the term schizophrenia

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    interviews
    Positive and Negative Symptom Score
    Psychosis
    stigma

Explanation

Question 7 of 23

1

Five dopaminergic pathways:
a) – controls motor function/movement
b) - pleasurable sensations, euphoria & delusions/hallucinations (positive sypmtoms)
c) - mediates cognition and affect (and negative symptoms)
d) - prolactin secretion
e) there's another one he didn't tell us it's name i don't think it's important??

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    Nigrostriatal
    Mesolimbic
    Mesocortical
    Tuberoinfundibular

Explanation

Question 8 of 23

1

Schizophrenia - the Dopamine Hypothesis.
Majority of symptoms explained by dysregulation of dopaminergic pathways:
- activity of mesolimbic pathway explains pos symptoms
- activity of mesocortical pathways explains cog, aff, neg symptoms
- activity of nigrostriatal and tuberoinfundibular

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    Integrated
    High
    Low
    Normal

Explanation

Question 9 of 23

1

Order these drugs from lowest affinity for D2 Rs (low potency, to highest affinity for D2 Rs (high potency); low being 1 and high being 4.
1.
2.
3.
4.

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    Haloperidol
    Prochlorperazine
    Clozapine
    Chlorpromazine

Explanation

Question 10 of 23

1

NMDA receptor hypofunction hypothesis:

There are NMDA receptors in the brain. NMDA receptors in the have glutamate projections. A glutamate projection is a pathway that uses glutamate, an neurotransmitter. Schizophrenia may be caused by activity in these glutamate projections.
When the glutamate projections are -active, downstream of the mesolimbic DA pathway does occur, meaning the DA pathway is . This causes positive symptoms.
Also low of the excitatory NT glutamate means , and DA pathways become . This may cause the cognitive, negative, and affective symptoms.

TLDR; Low activity of in the causes low activity of in connected pathways, causing high activity in the and low activity in the .

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    cortical brainstem
    descending
    excitatory
    low
    hypo
    inhibition
    not
    mesolimbic
    hyperactive
    activity
    tonic excitation is lost
    mesocortical
    hypoactive
    NMDR receptors
    brainstem
    glutamate
    mesolimbic pathway
    mesocortical pathways

Explanation

Question 11 of 23

1

Therapy - Antipsychotics
• Note that DA (e.g. methamphetamine) can produce behavioural phenomenon indistinguishable from acute schizophrenia, so this supports the dopamine hypothesis
• Nearly all antipsychotics are but some also block to varying degrees
• Potency correlates with at D2 receptors - not but dose correlate effectiveness.
• “Typicals” are effective at treating symptoms vs “atypicals”
• Days/weeks/months to work suggests effects e.g.

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    agonists
    overactivity
    D2 antagonists
    5-HT2A
    activity
    not
    negative
    secondary
    ↑ D2 receptors in limbic structures
    less

Explanation

Question 12 of 23

1

“Typical” antipsychotics – D2 antagonists - and how they affect the dopaminergic pathways:
1. Mesolimbic - reduces to activity, stopping positive symptoms and the response.
2. Mesocortical - still low activity
3. Nigrostriatal - reduced to activity, explains side effects
4. Tuberoinfundibular - to low activity, explains elevated

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    normal
    pleasure/reward
    low
    parkinsonian
    reduced
    prolactin

Explanation

Question 13 of 23

1

‘Typicals’ aka ‘First generation antipsychotic’ side effects:
- Extrapyramidal side effects – direct block of nigrostriatal DA receptors
- Muscle spasm within hours, can be fatal
- subjective tension & need to move, objective restlessness, distress
• Pseudo-Parkinsonism - gait disturbance
• Tardive Dyskinesia - movements, reversible?
- Dry , blurred , constipation, weight , sedative, -prolongation, dyscrasia’s, postural , elevated prolactin
- Sexual common with both typical and ‘atypicals’

Role in current treatment - history of response, of depots, good for management e.g. chlorpromazine, haloperidol, zuclopenthixol, fluphenazine.

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    Dystonia
    Akathisia
    rigidity, tremor, bradykinesia,
    abnormal involuntary
    mouth
    vision
    gain
    QT
    hypotension
    dysfunction
    range
    good
    acute

Explanation

Question 14 of 23

1

“Atypical” antipsychotics
• D2 antagonists AND - defining property of ‘atypicals’
• Critically, likely to induce dystonia/akathisia/ in the antipsychotic naïve
• Reduced symptoms in contrast to the ‘typicals’- debatable?
• Perceived side effects with atypicals? e.g. olanzapine, risperidone etc.
• Metabolic syndrome - weight , elevated , insulin , diabetes
• Less effect on prolactin - except
• ~ 30-50% of all patients are treatment-resistant to varying degrees and need

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    5-HT2A antagonism
    less
    Parkinsonism
    negative
    less common
    gain
    lipids
    resistance
    risperidone
    clozapine

Explanation

Question 15 of 23

1

Antipsychotic antagonism of WHICH RECEPTORS is associated with weight gain?

Select one of the following:

  • 5-HT2c & H1

  • 5-HT2c & H2

  • 5-HT1a & H1

  • 5-HT1a & H2

Explanation

Question 16 of 23

1

Antipsychotic M3 antagonism impairs:

Select one of the following:

  • insulin regulation

  • prolactin regulation

Explanation

Question 17 of 23

1

Which of these drugs is MOST likely to cause hypotension?

Select one of the following:

  • Chlorpromazine

  • Haloperidol

  • Quetiapine

Explanation

Question 18 of 23

1

Which 2 drugs are the most sedating?

Select one of the following:

  • Chlorpromazine, Clozapine

  • Clozapine, Olanzapine

  • Olanzapine, Zuclopenthixol

Explanation

Question 19 of 23

1

Which 3 drugs are most likely to cause extra-pyrimidal SEs?

Select one of the following:

  • Zuclopenthixol, Haloperidol, Chlorpromazine

  • Chlorpromazine, Risperidone, Aripiprazole

  • Aripiprazole, Zuclopenthixol, Haloperidol

Explanation

Question 20 of 23

1

Treatment resistant schizophrenia
• Defined by - treatment with a minimum of antipsychotics for at least weeks at maximum dose
• Occurs in ~% of patients with schizophrenia
• Clozapine induces remission in ~% of patients with TRS, and is the only antipsychotic shown to decrease rates, and increase rate of living
• Takes about 9 on average post-first-psychotic-episode before used in NZ due to significant side effects - during this time patients typically have very poor quality of life

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    2
    6
    tolerated
    30
    30-50
    suicide & re-hospitalization
    independent
    years

Explanation

Question 21 of 23

1

Which of these is NOT a side effect of clozapine?

Select one of the following:

  • Tachycardia

  • Hypotension

  • Seizures

  • Constipation

  • Weight gain

  • Hypersalivation

  • Nausea and vomiting

  • Sedation

  • Diarrhoea

Explanation

Question 22 of 23

1

Clozapine monitoring:
- Verbal for - toxic megacolon risk
- Blood monitoring for (0.8% of patients, during the first year peaks at 8-10 weeks of Tx) and (3-4%)
• Monitor for the first 18 weeks, then every 2 weeks for the remainder of the year, then
• 2.4 fold higher incidence in versus caucasians with a 5% increase in risk/decade
% experience a further issue following re-challenge after neutropenia...
• NO re-challenge following

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    constipation
    agranulocytosis
    neutropenia
    weekly
    monthly
    Asians
    38
    agranulocytosis or myocarditis

Explanation

Question 23 of 23

1

Clozapine Interactions
• Metabolised by CYP450 1A2 and less so by 2D6)
– levels decreased by high levels of , cigarette smoking
- levels increased by ,
may increase sedation and respiratory depression
may increase constipation risk, pyrexia
• Evening oil and may increase seizures
may exacerbate ADRs

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    caffeine, valproate, carbamazepine
    clarithromycin, rifampicin, erythromycin
    fluoxetine, paroxetine
    Benzodiazepines
    Anticholinergics
    primrose
    tramadol
    Lithium

Explanation