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

Differential Diagnosis of
Psychosis
Prescription medications causing symptoms-
anticholinergic medications
Illicit drugs intoxication from
methamphetamines, cocaine, PCP,
hallucinogens, or withdrawal from alcohol, or
benzodiazapenes - xanax, ativan
Medical conditions like seizure, CNS infections,
neurosyphilis, brain tumors
Metabolic abnormalities thyroid disease,
nutritional deficiencies
Definition of Psychosis:
Mental Status
Break from reality evidenced by delusions,
hallucinations, illusions, disordered thinking, loss
of ego boundaries, or failed reality testing
Affects thought content or thought process
A symptom of various disorders, but not a
disorder in itself
Lifetime prevalence of 3% in the US

On the mental status
exam: Thought Content
Delusions: fixed, false beliefs based on an
incorrect reference about an external reality that
fail to correct with reasoning & are inconsistent
with patients education/culture
Types 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
On the mental status
exam: Distorted
perceptions
Hallucinations: a sensory perception that has the
compelling 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 misperceived
or misinterpreted
What about during
Dreams?
Hypnagogic: when falling asleep
Hypnopompic: when awakening
Illogical Thought Process

Circumstantiality
Tangentiality
Derailment
Loose associations
Thought blocking
Neologisms made up words

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
Schizophrenia
Functionally impaired patients with at least 2
characteristic symptoms (delusions,
hallucinations, disorganized or catatonic
behavior, or negative symptoms) with effects
lasting at least 6 months.


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
Negative Symptoms
A diminution or loss of normal function
Decreased emotional expressivity (affective
flattening)
Restricted speech fluency
Alogia restricted thought production
Avolition decreased goal directed behavior
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
Neuroimaging and
Dopamine
Related to dopaminergic tone
Newer 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)

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
Glutamate
May be associated with pathophysiology of
schizophrenia
People intoxicated with glutamate receptor
agonists (PCP, ketamine) exhibit behavioral
signs like schizophrenia including positive &
negative symptoms
These drugs bind to the NMDA class of glutmate
receptors

GABA
The effects of NMDA antagonists thought to be meditated
through GABA release
NMDA receptors are found on GABAergic inhibitory
interneurons
Activating NMDA receptors causes increased GABA
release suppression of glutmate release
In schizphrenia: binding of antagonist on NMDA receptor
on GABA inhibitory receptor causes increased
glutamatergic state which is thought to cause symptoms of
psychosis
Higher order cognitive deficits in schizophrenia thought to
be linked to GABA dysregulation
Antipsychotics
Typicals: Older, Motor side effects, more potent

Atypicals: Newer, metabolic side effects, less
potent


Typical Antipsychotics
Haldol
Developed in the 1950s
Was the most widely used antipsychotic for
schizophrenia
Increases neuronal activity throughout the basal
ganglia
No linear relationship between dose and
antipsychotic action
Atypicals
Risperdone: higher risk of EPS than other
atypicals (especially akathesia) & dose
dependent. Weight gain, and prolactin elevation
Olanzapine (Zyprexa): there is no increased
Dopamine 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
Atypicals
Aripiprazole (Abilify): clinically less effective for
positive symptoms, lower risk of weight gain or
EPS
Ziprasidone (Geodon): clinically less effective for
positive 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

D2 Receptor Affinities
Receptor Seroquel Zyprexa Risperda
l
Abilify Haldol
D2 + ++ +++ ++++ ++++
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
Extrapyramidal side effects

Directly related to D2 receptor blockade in
nigrostriatal pathway, balanced by excitatory
cholinergic activity
Acetylcholine works in conjunction with
dopamine to produce movement.
Smooth muscle control requires a balance of
dopamine & acetylcholine
High potency, typical antipsychotics > low
potency, typical antipsychotics > modern, atypical
antipsychotics at modest doses
Takeaway Point
In psychosis, Dopamine INCREASED
Antipsychotic medications DECREASE
dopamine
Side effects of antipsychotic medications can
cause DOPAMINE DEPLETION, & movement
dysfunction (like Parkinsons disease, which is a
movement disorder)
To treat side effects, we use medications that
DECREASE acetylcholine (which effectively
INCREASES Dopamine & restores balance)
EPS symptom
Acute dystonia Intermittent but
sustained muscle
spasms leading to
involuntary
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 disorder
involving involuntary
movements of mouth,
tongue and upper
extremities after
chronic antipsychotic
use
Treated with
clozapine, reducing
antipsychotic dose
Video of Bipolar &
schizophrenia

References
The American Psychiatric Publishing Textbook of
Psychiatry, 5
th
edition
Gabbards Treatment of Psychiatric Disorders, 4
th

edition