#97 - Psychosis (1.5 hours) Flashcards by Jordan Harbaugh-Williams

define psychosis and its core symptoms

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

How well did you know this?

Not at all

Perfectly

Broad overview of neural circuit dysfunction in schizophrenia

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

How well did you know this?

Not at all

Perfectly

What category of disease is schizophrenia?

neurodevelopmental disorder, with genetic and environmental risk factors.

How well did you know this?

Not at all

Perfectly

What are the positive symptoms of schizophrenia?

delusions

- hallucinations

How well did you know this?

Not at all

Perfectly

What are the negative symptoms of schizophrenia?

flat affect (lack of range of emotion)
alogia (decreased speech)
avolition (loss of motivation)

How well did you know this?

Not at all

Perfectly

What is the primary mechanism of antipsychotic medications?

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

How well did you know this?

Not at all

Perfectly

Which antipsychotic does not block the D2 dopamine receptor?

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

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

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)

How well did you know this?

Not at all

Perfectly

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

clozapine

How well did you know this?

Not at all

Perfectly

What is the primary dangerous side effect of clozapine?

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

myocarditis
orthostatic hypotension and tachycardia.

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

How does potency relate to side effects?

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

How well did you know this?

Not at all

Perfectly

Review: what is agranulocytosis?

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

How well did you know this?

Not at all

Perfectly

Which antipsychotics are low potency?

Chlorpromazine

How well did you know this?

Not at all

Perfectly

Which antipsychotics are high potency??

haloperidol and fluphenazine

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

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

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

which neurotransmitters are involved in schizophrenia?

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

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

secondary auditory association cortex (hyperactivated in schizophrenia)

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?

emotional regulation / attention structures cause hallucinations when HYPERACTIVE

Monitoring/ volitional function centers cause hallucinations when HYPOactive.

what is thought withdrawal?

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

what is thought insertion?

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

What are delusions of reference?

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

What are some examples of delusion?

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

What is a very broad mechanism of delusions?

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

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

Salience (delusions of reference) Agency/others Fear / Paranoia Pre-frontal cortex and Midbrain are involved in them all!!

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

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

What changes occur in neurodevelopment in a schizophrenic brain?

- excessive excitatory pruning - reduced prefrontal inhibitory synapses - deficient myelination

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

increased dopamine in the mesolimbic pathway = positive symptoms

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

decreased dopamine in the mesocortical pathway.

heritability of schizophrenia

80%

definition of heritability

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

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

TRUE!

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

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

What are example types of "rare" genetic variants in schizophrenia?

- mutations (large) - CNVs (copy number variants) IMPORTANT: rare genetic variations have larger odds ratios than the common genetic variations!!

What are the 2 most important genes in schizophrenia?

22q11 deletion | DISC1 gene

How does 22q11 deletion cause schizophrenia? protein/pathway

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?

How does DISC1 gene mutation cause schizophrenia?

- 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!

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

schizophrenia = chronic (constantly affected) with exacerbations. bipolar = periods of normal (different from schizophrenia) - with relapses of mood disturbances. They are possibly on a continuum...

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?

Risperidone -also associated with amenorrhea and hyperprolactinemia Due to the tuberoinfundibular pathway.

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

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..

Which drugs are associated with weight gain?

clozapine, olanzapine, other 2nd gen drugs.

Which side effects are worse in 2nd gen drugs?

Neuroleptic side effects. - weight gain - increased blood pressure/lipids/blood sugar.