Block 3 PSYCH Exam -- Shizo & Psychotic Disorders (# 11-12)
Terms
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- % of U.S. population w/ Schizophrenia
- 1%
-
% of schizo pts. that attempt suicide
% of schizo pts. that die by suicide -
30%
10% - DSM (short) definition of Schizophrenia
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Decline in functioning
6 months or greater of symptoms (at least 1 month active) - Schizophreniform Disorder
-
Same criteria as schizophrenia, BUT SHORTER
1 - 6 MONTHS - Brief Psychotic Disorder
- < 1 MONTH
- Schizoaffective Disorder
-
Criteria for BOTH schizo and Mood disorder
Symptoms occur together
Preceded/followed by >= 2 weeks of delusions W/O mood symptoms - Delusional Disorder
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NON-bizarre delusions >= 1 month
ABSENCE of other active-phase Schizo symptoms
NOTE: this is often MORE REFRACTORY to anti-psych meds - Shared psychotic disorder (Folie a deux)
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Disturbance in individual influenced by someone w/ an established delusion
Disturbances have similar content - What is a positive symptom
- Symptom that is present in schizophrenia, but NOT seen in normal people
- What is a negative symptom
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Area where schizo pt. is lacking normal abilities
Also called "deficit" symptom - Which type of schizo symptom do traditional anti-psychotics affect LESS?
- Negative symptoms
- Prevalence of positive symptoms in Type I vs Type II schizo
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Type 1 -- Prominent positive symptoms
Type 2 -- LESS prominent positive symptoms - Premorbid functioning in Type I vs. Type II schizo
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Type 1 -- GOOD premorbid functioning
Type 2 -- POOR premorbid functioning - Onset in Type I vs. Type II schizo
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Type 1 -- ACUTE
Type 2 -- INSIDIOUS - Efficacy of traditional antipsychotics in Type I vs Type II schizo
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Type 1 -- responds to traditional anti-psychotics
Type 2 -- poor response - Cognition in Type I vs. Type II schizo
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Type 1 - Good cognition between episodes
Type 2 - Prominent cognitive impairment - Neuroimaging in Type I vs. Type II schizo
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Type 1 -- Normal
Type 2 -- Atrophy & enlarged ventricles - Three Dimensions of the 3-D model os Schizo
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Psychotic
Disorganized
Negative - Time frame of disturbance/symptoms to qualify as Schizo
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6 MONTHS of signs of the disturbance
At least 1 MONTH of two or more of following:
Delusions, hallucinations, disorganized speech
Disorganized/catatonic behavior
Negative symptoms - When is only ONE Criterion A symptom required for a diagnosis of Schizo?
-
When delusions are bizarre
OR
Hallucinations are a running commentary or >= 2 voices conversing - Does Schizophrenia have any mood components?
- NO
- When can Schizo be classified in terms of its longitudinal course?
- Only after at leat 1 year has elapsed since onset
- Paranoid Type Schizo
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One or more delusions or frequent auditory hallucinations
Doesn't meet criteria for other types - Disorganized Type Schizo
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ALL of the following are prominent:
Disorganized speech
Disorganized behavior
FLAT/INAPPROPRIATE AFFECT
Criteria is not met for Catatonic Type - Catatonic Type Schizo
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AT LEAST TWO of the following:
Motoric immobility
Excessive motor activity
Extreme negativism
Peculiarities of voluntary movment
Echolalia or echopraxia - Undifferentiated Type Schizo
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Criterio A Schizo symptoms are present
BUT, doesn't fit any subtype - Residual Type Schizo
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Continued evidence of the disturbance
Indicated by negative symptoms OR two or more Criterion A symptoms - Criterion A symptoms for Schizo (5)
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Hallucinations
Delusions
Negative symptoms
Disorganized speech
Disorganized/catatonic behavior - Age of onset of Schizo in men? women?
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Men - early to mid 20s
Women - late 20s - Prodromal phase of Schizo
- Gradual development of NEGATIVE symptoms
- Active phase of Schizo
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Development of POSITIVE symptoms
Often occurs abruptly -- PSYCHOTIC BREAK - Akinetic Depression
- Depression presenting in Schizo from anti-psychotic-induced Parkinsonism
- Typical course of Schizo
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EPISODIC exacerbations
CHRONIC social disability
Negative symptoms get worse with time
Positive symptoms often lessen with time - Good prognostic factors in Schizo
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Good premorbid adjustment
Acute onset
Precipitating events
Being FEMALE
FAMILY HISTORY OF MOOD DISORDER
NO family history of Schizo - Relapse rate if pts. stop taking their meds
- 10% PER MONTH
- Ultimate relapse rate w/o meds
- 70%
- Relapse rate for pts. who are compliant w/ meds
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30 - 50%
15% in the 1st yr. - Family risks of Schizo
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One parent - 5-6%
One sibling - 10%
One sibling & parent - 17%
Two parents - 46% - Risk in twins for Schizo
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Dizygotic - 15%
Monozygotic - 50% - What does Dopamine Theory of Schizo postulate?
- That Schizo is due to EXCESS Dopamine
- Problems w/ "classic" DA theory
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NOT cofirmed by CNS studies
Doesn't explain negative symptoms
Cocaine psychosis resembles POSITIVE symptoms, NOT NEGATIVE
D2 blocking antipsychotics may actually exacerbate negative symptoms - In addition to being weak D2 blockers, what do ATYPICAL antipsychotics block
- They are serotonin antagonists
-
How do atypical antipsychotics compare to traditional ones?
(in terms of symptoms they treat) -
More effective against positive symptoms
(PSYCH notes)
More effective against negative symptoms
(PHARM notes) - Mesolimbic tract
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Involved in "reward circuitry"
Overstimulation may lead to hallucinations/delusions
D2 blockers may work here to treat POSITIVE symptoms - Nigrostriatal tract
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Degeneration of this --> Parkinson's
Increased DA activity --> choreoform, dystonic movements
Increased D2 sensitivity here is responsible for Tardive Dyskinesia - Mesocortical tract
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Mediates effects of DA on attention & planning
Involved in GABA-mediated feedback on brainstem DA neurons - Neuroimaging in Schizo shows decreased activity where?
- Frontal lobe
- Tuberoinfundibular tract
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DA here INHIBITS prolactin release
SO, blockade --> Increased prolactin --> galactorrhea
Antipsychotics suppress LH & FSH (can cause amenorrhea, anorgasmia) - Efficacy wise, how do traditional antipsychotics stack up against each other?
- They are all equally efficiacious
- Receptor types that traditional anti-psychotics interact with
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Histamine-1
Alpha-1
M1 ACh
D2 - blockade causes EPS, Inc. prolactin - Type of relationship between ACh and DA in nigrostriatal pathway
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Reciprocal
DA neurons synapse on ACh neurons --> Decr. ACh release
D2 blockade --> Inc. ACh --> EPS - Benztropine or Trihexyphenidyl
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Anti-cholinergic drugs that reduce Parkinsonism
Do so, W/O affecting anti-dopaminergic effect - Akathisia
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Severe motor restlessness
Very common
LESS responsive to anti-cholinergic medication - Acute Dystonia
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Sustained, involuntary muscle spasms
Most often involves muscles of face/neck - When does acute dystonia usually occur?
- During 1st week of treatment with previously unexposed pts.
- In what situation(s) is acute dystonia more common (2)?
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Young male patients
High potency medications - How is acute dystonia treated (2)?
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Anticholinergic (benztropine)
OR
Antihistamine (diphenhydramine)
Many clinicians start antichilinergics before antipsychotics - What parts of body are most likely involved in tardive dyskinesia?
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Tongue & Jaw
Limbs (50%) -
Incidence of tardive dyskinesia
(age groups) -
Younger pts. - 5% per yr.; 20-30% after several yrs.
Older pts. - 30% 1st yr.; 50% w/ long-term treatment - Who usually first notices TD?
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Clinician
TD is subtle, so if often missed by patients and their families
TD is usually NOT progressive - Risk factors for TD
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Age
Greater number of drug holidays
Mood Disorder > Schizophrenia - What can TD be masked by
- INCREASED dose of anti-psychotic
- Which pts. is spontaneous dyskinesia more common in?
- Pts. w/ prominent negative symptoms and cognitive dysfunction
- What can you do to resolve TD?
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Gradual taper off of traditional anti-psychotics
Switch to atypical antipsychotics - Sex predilection for TD
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Equal prevalence among young men and women
More common in elderly women than in men - When does neuroleptic malignant syndrome usually develop?
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Within a month of first starting on antipsychotics
Most often within the first week - Treatment for NMS
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Sepsis workup
Discontinuation of meds
Anitpyeretics, IV fluids, COOLING BLANKETS
DA agonists (bromocriptine)
Muscle relaxants (dantrolene)
ECT is primary treatment strategy - How long does neuroleptic malignant syndrome take to resolve?
- Typically about 2 weeks
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How do traditional antispychotics worsen symptoms?
(pathway effects) -
DECREASED nigrostriatal DA --> Parkinsonism
DECREASED mesocortical DA --> problems w/ attention and planning - What relationship does 5-HT have to the nigrostriatal DA system?
- It inhibits it
- What relationship does 5-HT have to the mesocortical DA system?
- Inhibits it
- What relationship does 5-HT have to the mesolimbic system?
- Does NOT play a role in it
- Key points about Clozapine
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Atypical antipsychotic
WEAK D2 blocker
STRONG 5HT2 blocker
Virtually NO EPS
Effective against negative symptoms
More effective for positive symptoms - Problems w/ Clozapine (6)
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Anti-histaminergic -- WEIGHT GAIN, Sedation
Anti-cholinergic
Anti-alpha-1
AGRANULOCYTOSIS -- NEEDS weekly CBC
Seizures
Hypersalivation - When is clozapine used?
- In treatment-resistant cases
- Risperidone key points
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Lower weight gain
MORE D2 antagonism
--- Greater risk of EPS (esp. > 6 mg/day)
--- Greater likelihood of prolactin elevation - Olanzapine (Zyprexa) key points
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Most likely to cause significant weight gain
Lower EPS than Risperidone
Also approved for treatment of mania (acute) - Quetiapine (Seroquel) key points
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Very low rate of EPS
Very little weight gain - Ziprasidone (Geodon)
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Lowest risk of weight gain
Very low rate of EPS
NOTE: can lengthen QTc interval
--- Need to examine ECG and other meds - Atypical antipsychotic (non-clozapine) w/ most significant weight gain
- Olanzapine
- Atypical antipsychotic w/ least significant weight gain
- Ziprasidone
- What (pathway wise) are positive symptoms mostly due to?
- Overactivity in the mesolimbic pathway
- What (pathway wise) are negative symptoms mostly due to?
- Underactivity in the mesocortical pathway
- Aripiprazole (Abilify) key points
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Dopamine System Stabilizer
5HT2A antagonist
5HT1A partial agonist
D2 PARTIAL AGONIST
Like adding lukewarm water to a tub - Most consistent CT/MRI finding in Schizo
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Ventricular enlargment & sulcal dilatation
NOTE: non-specific
Remember, also found in Stage 3 Alzheimer's
NOTE: statistical finding; scans can also be normal - What brain finding in Schizo pts. correlates w/ auditory hallucinations?
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Temporal lobe atrophy
Especially in superior temporal gyrus - Common EEG finding in Schizo pts.
- Blunting and delay of P300 wave
- In Northen latitudes, Schizo is more common in what people?
- Those born in the winter
- Progression of symptomology after insult to mesocortical pathway
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Negative symptoms first
Ultimately, decreased negative feedback to limbic system
Decreased feedback --> positive symptoms - Erotomanic subtype of delusional disorder
- Believes another person, of higher status, is in love with them
- Persecutory subtype of delusional disorder
- Pt. is being malevolently treated somehow
- Somatic subtype of delusional disorder
- Pt. has some physical defect or medical condition
- Which atypical anti-psychotic can lengthen the QTc interval?
- Ziprasidone