Psychosis

Compton 2020
jcompton@health.ucsd.edu
Preamble
• What is “The Mind” ?

• What is “Consciousness”?

• What is “Reality”?
I. Psychosis
History
• “Madness”
• In western civilization was thought to be caused by
demonic possession.
• “Psychic neurosis” – Canstat 1841
• “Psychosis” – Feuchtersleben 1845
• Melancholia, mania, dementia, idiocy.
• Historically used synonymously with “psychopathy”.
• Greek for ‘disease of the spirit’.
• “Mental illness”, “Insanity” – Flemming 1859
• Organic findings of diseases of the soul.
• Psychosis as a phenomenological diagnosis –
Jaspers 1913
“Men ought to know that from the
brain, and from the brain only, arise
our pleasures, joys, laughter, and
jests, as well as our sorrows, pains,
griefs and tears. Through it, in
particular, we think, see, hear, and
distinguish the ugly from the
beautiful, the bad from the good,
the pleasant from the unpleasant….
It is the same thing which makes us
mad or delirious, inspires us with
dread and fear, whether by night or
by day, brings sleeplessness,
inopportune mistakes, aimless
anxieties, absentmindedness, and
acts that are contrary to habit.”
- Hippocrates
DSM
• Phenomenological
• Defined by the experiences of the patient’s consciousness
• Based on SYMPTOMS
• Subjective report from patient vs objective observation from
psychiatrist
• Communication
• Used for research, for guiding treatment, for billing…
• Subject to change based on cultural and political
influences
• DSM diagnoses do not exist per se as a disease
entity in reality
Modern Conceptualization of Psychosis
“Impairment of thought such that
contact with reality is lost”
• Cardinal Symptoms:
• Hallucinations
• Delusions
• Other Symptoms:
• Disorganization
• Thought, speech, behavior
• Negative symptoms
• Cognitive
• Loss of Insight
Hallucinations
• Auditory
• Dopamine-mediated
• Primary psychotic disorder
• psychostimulants
• Visual
• Serotonin-mediated
• Delirium, “organic” psychosis
• Psychedelics, alcohol withdrawal
• Tactile
• Psychostimulants
• Olfactory
• Epilepsy
• Gustatory
Dopamine & Aberrant Salience
• Dopamine mediates
Salience in the
Mesolimbic Pathway
• Conversion of neural
representation of
external stimuli into
an attractive or
aversive drive
• Not simply a
“reward” or
“pleasure” center
Delusions
Defining a delusion:
• A belief that is clearly false and that
indicates an abnormality in the
patient’s content of thought.
• The false belief is not accounted for
by the patient’s culture, religion,
background or intelligence.
• A delusional patient will hold firmly
to the belief regardless of evidence
to the contrary.
Delusions
• Paranoid
• Persecutory
• Reference
• Thought broadcasting
• Somatic
• Grandiose
• Erotomania
• DeClerambault
• Misidentification
• Caprgas, Fregoli
• Nihilistic
• Cotard
• Folie a’ deux
Disorganization
Disorganization
Negative Symptoms
• Flat affect
• Thought blocking
• Avolition
• Alogia
• Anhedonia
• Asociality
• Attentional deficits
• “Autism”
Cognitive
Causes of Psychosis
• Psychiatric disorders
• “Schizophrenia”
• “Schizoaffective disorder”
• “Delusional disorder”
• “Bipolar with psychotic features”
• “Depression with psychotic features”
• “Postpartum psychosis”
• “Substance-induced psychosis”
• Neurological disorders
• Encephalitis (autoimmune, infectious)
• NMDA
• Neurocognitive/ dementia
• Injury: anoxic, stroke, TBI…
• Delirium, encephalopathy
• Other medical illness
• Vitamin D, thyroid, autoimmune, viral…
• Intoxication
NMDA receptor encephalitis
II. Schizophrenia
Schizophrenia – “Split Mind”
• Emil Kraepelin – Dementia Praecox
“The causes of dementia praecox are at the present
time still mapped in impenetrable darkness”

• Eugene Blueler – Schizophrenia

• four primary symptoms (the four As) were
abnormal associations, autistic behavior and
thinking, abnormal affect and ambivalence
“My patients are stranger to me than the birds in
my garden. But if they're strangers to us, what are
we to them?”
Natural History
Genetic / Stress model
• High heritability
• Overlap between risk alleles for
schizophrenia and immune genes
• “Second hit”
• Intrauterine
• Autoimmunity
• Infection (2nd trimester influenza, etc)
• Winter births
• Decreased brain asymmetry
• Developmental
• Early cannabis use
• Psychosocial stress
• Dopaminergic psychostimulant use
• Head injury
Genetic / Stress model
Schizophrenia - Neurodevelopmental model
Schizophrenia - Neurodevelopmental model
Schizophrenia - Neurodevelopmental model
Neuroinflammatory model
• Mild Encephalitis
• Low Level Neuro-
Inflammation
• “late hit” of infection,
autoimmunity leads
to psychosis and brain
volume loss
• Large overlap
between risk alleles
for schizophrenia and
immune system
Schizophrenia - Neurodegenerative

Unable to independently
maintain stable housing

Requiring Hospitalization
Neurodegenerative
• Brain volume loss
• Prefrontal cortex
• Temporal lobe
• Hippocampus, parahippocampal
gyrus, amygdala
• Basal ganglia, thalamus
• Loss of cortical GABA neurons
• *Some* studies have found
increased annual brain volume
loss with use of antipsychotics!
DSM-5
• The presence of 2 (or more) of the following, each present for a significant portion of time during a 1-month
period (or less if successfully treated), with at least 1 of them being (1), (2), or (3): (1) delusions, (2)
hallucinations, (3) disorganized speech, (4) grossly disorganized or catatonic behavior, and (5) negative
symptoms
• For a significant portion of the time since the onset of the disturbance, level of functioning in 1 or more major
areas (eg, work, interpersonal relations, or self-care) is markedly below the level achieved before onset;
when the onset is in childhood or adolescence, the expected level of interpersonal, academic or occupational
functioning is not achieved
• Continuous signs of the disturbance persist for a period of at least 6 months, which must include at least 1
month of symptoms (or less if successfully treated); prodromal symptoms often precede the active phase, and
residual symptoms may follow it, characterized by mild or subthreshold forms of hallucinations or delusions
• The disturbance is not attributable to the physiologic effects of a substance (eg, a drug of abuse or a
medication) or another medical condition
• If there is a history of autism spectrum disorder or a communication disorder of childhood onset, the
additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition to the
other required symptoms or schizophrenia are also present for at least 1 month (or less if successfully treated)
Schizoaffective Disorder
Diagnostic criteria
• There must be overlap of psychotic symptoms and mood symptoms
• There must be the presence of psychosis without mood symptoms
• Mood symptoms are a prominent and enduring part of clinical picture (not just
one depressive episode, etc.)
Easy ways to conceptualize it:
• Schizophrenia with periods of depression and/or mania that occurs during
patient’s period of psychosis.
• The progression of a severe schizophrenia or bipolar illness such that the the two
separate diseases start to overlap (both involve the limbic system and frontal
lobes)
Delusional Disorder
• Delusion(s) without hallucinations or disorganization
• Persecutory delusions most common
• Perceptual disturbances are possible
• Appropriate affective response to delusions
• Preserved personality and cognition
• Relatively well functioning

• Very difficult to treat

Psychosocial
• Insanity
• “Illegal to be sick”
• Schizophrenogenic mothers
• Antipsychiatry movement
• Foucault
• Schizophrenics just think differently—it’s the
enforcement of cultural norms which makes them
suffer
• Antipsychotic medications are worse than the disease
• “Psychotic break”
• Psychosis conceptualized as a symptom of
Western Civilization
• In a tribal society, schizophrenics would be revered as
shamans
Questions?