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MOHD 4 Exam 5 > #97 - Psychosis (1.5 hours) > Flashcards

#97 - Psychosis (1.5 hours) Flashcards

1
Q

define psychosis and its core symptoms

A

Psychosis is a loss of contact with reality and consists of delusions, hallucinations, and/or disorganization in speech/thoughts/behaviors.

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2
Q

Broad overview of neural circuit dysfunction in schizophrenia

A

Alterations in GABA and glutamate signaling ultimately lead to dysfunctions in dopaminergic pathways, which contribute to positive and negative symptoms of schizophrenia.

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3
Q

What category of disease is schizophrenia?

A

neurodevelopmental disorder, with genetic and environmental risk factors.

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4
Q

What are the positive symptoms of schizophrenia?

A
  • delusions

- hallucinations

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5
Q

What are the negative symptoms of schizophrenia?

A
  • flat affect (lack of range of emotion)
  • alogia (decreased speech)
  • avolition (loss of motivation)
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6
Q

What is the primary mechanism of antipsychotic medications?

A

All antipsychotics (except aripiprazole, block the D2 dopamine receptor.

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7
Q

Which antipsychotic does not block the D2 dopamine receptor?

A

aripiprazole - it is the only one. (it is a partial D2 agonist).

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8
Q

What are the main side effects of antipsychotics due to dopamine blockade?

A
  • parkonsinism
  • dystonia (abnormal mm tone)
  • akathisia (feeling of restlessness/increased mvmt)
  • tardive dyskinesia
  • can make negative / cognitive symptoms worse, due to decreasing dopamine in mesocortical pathway
  • galactorrhea/ gynecomastia/ amenorrhea
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9
Q

What are the main side-effects of antipsychotics due to neuroleptic effects (ie, at other receptors)

A

anticholinergic (dry mouth, urinary retention, constipation, blurry vision)

antihistamine (sedation/ weight gain)

alpha-1 adrenergic blockade (sex dysfunction)

QTc prolongation

Increased blood pressure, lipid and blood sugar (especially 2nd gen)

Neuroleptic malignant syndrome (very bad - muscle rigidity, fever, autonomic instability)

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10
Q

Which anti-psychotic is the only one shown to be more efficacious, but reserved for treatment-resistant schizophrenia due to its side effects??

A

clozapine

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11
Q

What is the primary dangerous side effect of clozapine?

A

agranulocytosis - mandates close monitoring of WBC and ANC (absolute neutrophil count)

  • myocarditis
  • orthostatic hypotension and tachycardia.
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12
Q

What are the similarities and differences between first (typical) and second (atypical) generation antipsychotics?

A

-efficacy is similar
-both types are
-2 gen (atypical): lower affinity for D2 receptor
2 gen (atypical) has significant serotonin antagonism

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13
Q

How does potency relate to side effects?

A

Low potency =
decreased dopamine side effects
-increased non-dopamine side effects

High potency =

  • increased side effects due to dopamine blockade
  • decreased side effects due to binding of other receptors
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14
Q

Review: what is agranulocytosis?

A

a deficiency of granulocytes in the blood, causing increased vulnerability to infection.

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15
Q

Which antipsychotics are low potency?

A

Chlorpromazine

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16
Q

Which antipsychotics are high potency??

A

haloperidol and fluphenazine

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17
Q

What are the common atypical / 2nd gen antipsychotics? Suffix? There are 9

A 
suffix = apine & idone
-asenapine
-clozapine
-olanzapine
-quetiapine
-lurasidone
-paliperidone
-risperidone
-ziprasidone
ANDDDDD
aripiprazole, the lone wolf partial D2 agonist
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18
Q

What are the common 1st gen/ typical antipsychotics.? Suffix? There are 6

A 
most have -azine suffix
-Chlorpromazine
-fluphenazine
-perphenazine
-thioridazine, 
-trifluoperazine
ANDDD
-haloperidol
19
Q

which neurotransmitters are involved in schizophrenia?

A

All of them!! GABA, Glutamate, and dopamine are the main ones, though.

20
Q

What is the area of the brain that is responsible for hallucinations?

A

secondary auditory association cortex (hyperactivated in schizophrenia)

21
Q

Which 2 groups of structures input into the secondary auditory association cortex/ language centers, and cause auditory hallucinations when they have an abnormal level of activity?

A

emotional regulation / attention structures cause hallucinations when HYPERACTIVE

Monitoring/ volitional function centers cause hallucinations when HYPOactive.

22
Q

what is thought withdrawal?

A

the perception that someone/something is taking thoughts from your mind. Example of delusion

23
Q

what is thought insertion?

A

Perception that thoughts are planted in your mind from external source/individual. Example of delusion

24
Q

What are delusions of reference?

A

The perception that messages from the tv/radio are meant specifically for you. Example of delusion

25
Q

What are some examples of delusion?

A 
paranoia/ persecution
conspiracy theories
grandue (think you're jesus)
passivity - someone is controlling you
thought withdrawal
thought insertion
thought broadasting
delusions of reference.
26
Q

What is a very broad mechanism of delusions?

A

“mismatches between expectations and experience” - aberrations in how the brain computes and responds to prediction errors.

27
Q

What are the three circuits for different delusions? Which structures are common to each circuit?

A

Salience (delusions of reference)

Agency/others

Fear / Paranoia

Pre-frontal cortex and Midbrain are involved in them all!!

28
Q

t/f: cognitive deficits are part of the diagnostic criteria for schizophrenia

A

FALSE. They are common, but not part of the diagnostic criteria.

29
Q

What changes occur in neurodevelopment in a schizophrenic brain?

A
  • excessive excitatory pruning
  • reduced prefrontal inhibitory synapses
  • deficient myelination
30
Q

what is the mechanism for positive symptoms?/what is the pathway/neurotransmitter in the brain affected?

A

increased dopamine in the mesolimbic pathway = positive symptoms

31
Q

What is the mechanism for negative symptoms?/what is the pathway in the brain affected?

A

decreased dopamine in the mesocortical pathway.

32
Q

heritability of schizophrenia

A

80%

33
Q

definition of heritability

A

proportion of variation in a phenotype due to genetic variation. IT IS NOT the proportion due to genetics compared to environment.

34
Q

t/f - thousands of genes have been identified that put you at risk for schizophrenia.

A

TRUE!

35
Q

T/F - common genetic variants are more important in schizophrenia, since they have larger effects (odds ratios)

A

FALSE. Common variants, like SNPs, have smaller effects than rare variants, like mutations/CNVs. They are equally important.

36
Q

What are example types of “rare” genetic variants in schizophrenia?

A
  • mutations (large)
  • CNVs (copy number variants)

IMPORTANT: rare genetic variations have larger odds ratios than the common genetic variations!!

37
Q

What are the 2 most important genes in schizophrenia?

A

22q11 deletion

DISC1 gene

38
Q

How does 22q11 deletion cause schizophrenia? protein/pathway

A

22q11 deletion results in decrease of DGCR8 protein expression, resulting in a lack of microRNA that normally suppresses mutations.

22q11 is common in other disorders, like nearly all genes associated with schizophrenia?

39
Q

How does DISC1 gene mutation cause schizophrenia?

A
  • translocation between chromosome 1 and 11
  • it impacts GSK3/ WNT signalling
  • it is associated with many other psychiatric illnesses (autism, bipolar, depression) - which is very common in schizophrenia genes!
40
Q

how does the course of schizophrenia differ from that of bipolar disorder?

A

schizophrenia = chronic (constantly affected) with exacerbations.

bipolar = periods of normal (different from schizophrenia) - with relapses of mood disturbances.

They are possibly on a continuum…

41
Q

a patient is treated with an antipsychotic. At 3 week follow up, he has gained 10 lbs, also notes gynecomastia(man boobs) and galactorrhea (milk discharge). What medication is he likely on?

A

Risperidone
-also associated with amenorrhea and hyperprolactinemia

Due to the tuberoinfundibular pathway.

42
Q

T/F: Antipsychotics are effective for positive and negative symptoms for schizophrenia.

A

FALSE. Only help with positive symptoms (delusions/ hallucinations). Since negative symptoms are due to lack of dopamine (mesocortical pathway), they do not help with them, actually they quite often make them worse..

43
Q

Which drugs are associated with weight gain?

A

clozapine, olanzapine, other 2nd gen drugs.

44
Q

Which side effects are worse in 2nd gen drugs?

A

Neuroleptic side effects.

  • weight gain
  • increased blood pressure/lipids/blood sugar.

MOHD 4 Exam 5 (13 decks)

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