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Psychosis
A symptom of severe psychiatric and non-
psychiatric (medical) disorders that may be short
lived or chronic
It is often misunderstood
The individual suffers a break in reality that
influences all aspects of their life
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Differential Diagnosis of
PsychosisPrescription medications causing symptoms-anticholinergic medications
Illicit drugsintoxication from
methamphetamines, cocaine, PCP,hallucinogens, or withdrawal from alcohol, orbenzodiazapenes - xanax, ativan
Medical conditions like seizure, CNS infections,
neurosyphilis, brain tumors
Metabolic abnormalitiesthyroid disease,nutritional deficiencies
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Definition of Psychosis:
Mental StatusBreak from reality evidenced by delusions,hallucinations, illusions, disordered thinking, loss
of ego boundaries, or failed reality testing
Affects thought contentor thought process
A symptom of various disorders, but not a
disorder in itself
Lifetime prevalence of 3% in the US
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On the mental status
exam: Thought ContentDelusions: fixed, false beliefs based on anincorrect reference about an external reality that
fail to correct with reasoning & are inconsistent
with patients education/cultureTypes include bizarre, delusional jealousy,
erotomanic, grandiose, persecutory, somatic, of
being controlled, thought broadcasting, thought
insertion
Ideas of reference: words or actions that have
personal, special meaning but not full delusions
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On the mental status
exam: Distorted
perceptionsHallucinations: a sensory perception that has thecompelling sense of reality of a true perception
but that occurs without external stimulation of the
relevant sensory organ.May or may not have insight
Mood congruent versus incongruent
Illusions: actual external stimulus is misperceivedor misinterpreted
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What about during
Dreams?Hypnagogic: when falling asleepHypnopompic: when awakening
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Illogical Thought Process
CircumstantialityTangentiality
Derailment
Loose associations
Thought blocking
Neologismsmade up words
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Schizophrenia
Serious and lifelong mental disorder
Affects 1% of population
Men >Women
Onset: Men 18-25, women 25-mid 30s
Urban born > rural born
Striking disturbances in mental functioning
Positive & negative signs and symptoms
Disruption in experience of reality
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Schizophrenia
Functionally impaired patients with at least 2
characteristic symptoms (delusions,
hallucinations, disorganized or catatonic
behavior, or negative symptoms) with effectslasting at least 6 months.
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Positive symptoms
an excess or distortion of normal functions
Delusions, hallucinations
Disorganized speech
Catatonic behavior: motoric immobility, excessive
motor activity, extreme negativism, mutism,
pecularities of voluntary movement, echolalia
Disorganized thinking (formal thought disorder)
that impairs effective communication
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Negative Symptoms
A diminution or loss of normal function
Decreased emotional expressivity (affective
flattening)
Restricted speech fluency
Alogiarestricted thought production
Avolitiondecreased goal directed behavior
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Dopamine Hypothesis
Thought that schizophrenia is by product of
dopamine dysregulation
Evidence from work in 1960s
Administering Dopamine agonists
amphetamine, produces symptoms like
schizophrenia
Most important Dopamine receptor is D2
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Neuroimaging and
DopamineRelated to dopaminergic toneNewer hypothesis states the there is a hyper-
dopamine state in the nigrastriatal D2 system
that causes the positive symptoms & hypo-dopamine state in prefrontal D1 system with
negative symptoms (cognitive problems)
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Limitations
Dopamine hypothesis does not account for
negative symptoms
Dopamine blockers (antipsychotics) not effective
in treating negative symptoms
Dopamine agonists do not induce negative
symptoms
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Glutamate
May be associated with pathophysiology of
schizophrenia
People intoxicated with glutamate receptor
agonists (PCP, ketamine) exhibit behavioralsigns like schizophreniaincluding positive &
negative symptoms
These drugs bind to the NMDA class of glutmate
receptors
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GABA
The effects of NMDA antagonists thought to be meditatedthrough GABA release
NMDA receptors are found on GABAergic inhibitoryinterneurons
Activating NMDA receptors causes increased GABAreleasesuppression of glutmate release
In schizphrenia: binding of antagonist on NMDA receptoron GABA inhibitory receptor causes increasedglutamatergic state which is thought to cause symptoms of
psychosis
Higher order cognitive deficits in schizophrenia thought tobe linked to GABA dysregulation
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Antipsychotics
Typicals: Older, Motor side effects, more potent
Atypicals: Newer, metabolic side effects, lesspotent
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Typical Antipsychotics
Haldol
Developed in the 1950s
Was the most widely used antipsychotic for
schizophreniaIncreases neuronal activity throughout the basal
ganglia
No linear relationship between dose and
antipsychotic action
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Atypicals
Risperdone: higher risk of EPS than other
atypicals (especially akathesia) & dose
dependent. Weight gain, and prolactin elevation
Olanzapine (Zyprexa): there is no increasedDopamine blockade after a certain dose, very
sedating, significant weight gain
Quetiapine (seroquel): Low EPS incidence, need
very high doses to get D2 blockade, otherwise
mostly sedation. Associated with hypotension
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Atypicals
Aripiprazole (Abilify): clinically less effective for
positive symptoms, lower risk of weight gain or
EPS
Ziprasidone (Geodon): clinically less effective forpositive symptoms, can have cardiac side effects
Clozapine: effective in otherwise poorly
responsive patients, requires strict monitoring
because of blood count effects, not associated
with TD
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D2 Receptor Affinities
Receptor Seroquel Zyprexa Risperda
l
Abilify Haldol
D2 + ++ +++ ++++ ++++
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Neurotransmitter Location of
Synthesis
Associated With
Acetylcholine Basal Nucleus of
Meynert
Dopamine Substantia nigra Schizophrenia,addiction
Norepinephrine Locus Ceruleus Depression, anxiety
Serotonin Raphe Nuclei Depression, chronic
pain
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Extrapyramidal side effects
Directly related to D2 receptor blockade innigrostriatal pathway, balanced by excitatorycholinergic activity
Acetylcholine works in conjunction withdopamine to produce movement.
Smooth muscle control requires a balance ofdopamine & acetylcholine
High potency, typical antipsychotics > lowpotency, typical antipsychotics > modern, atypicalantipsychotics at modest doses
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Takeaway Point
In psychosis, Dopamine INCREASED
Antipsychotic medications DECREASEdopamine
Side effects of antipsychotic medications cancause DOPAMINE DEPLETION, & movementdysfunction (like Parkinsons disease, which is amovement disorder)
To treat side effects, we use medications thatDECREASE acetylcholine (which effectivelyINCREASES Dopamine & restores balance)
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EPS symptom
Acute dystonia Intermittent but
sustained muscle
spasms leading toinvoluntary
movements
Treated with
anticholinergic
medication in IV form
Akathesia Sensation of motor
restlessness
associated with a
strong desire to move
lower extremity
Treated with beta
blocker
Parkinsonism Rigidity, bradykinesia,
tremor, masked
facies, shuffling gait
Treated with
anticholinergic
medication
Tardive dyskinesia Movement disorderinvolving involuntary
movements of mouth,
tongue and upper
extremities after
chronic antipsychotic
use
Treated withclozapine, reducing
antipsychotic dose
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Video of Bipolar &
schizophrenia
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References
The American Psychiatric Publishing Textbook of
Psychiatry, 5thedition
GabbardsTreatment of Psychiatric Disorders, 4th
edition
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