25 Notes: Schizophrenia – biologicalpsych.com

Psychotic disorders
“The Schizophrenias”
1% incidence
More likely in US & Europe
- 10 to 100 times
Slightly more common in men
Earlier onset, more severe
Originally: dementia praecox
- Eugen Bleuler called it schizophrenia in 1911
Starts as teens or early adult
- Typical onset 16 to 30
- Uncommon onset over 45
Symptoms vary
- Seem OK until share thoughts
- Sit without moving…for hours
Episodes
- Typical: not more than 6 weeks
- Symptoms come & go
- Hallucinations
  - Lasts a few days
  - Feel agitated
- Delusions
  - Lasts a few months
Range of severity
- Hospitalized
- Meaningful lives in communities
3-Factor Model
- Disorganized thinking
- Distorted thinking
  - Delusions & hallucinations
- Disconnected mind-motor
  - Spontaneous movement
  - Fluid speech
  - Self control
Positive symptoms
- Unique to schizophrenia
  - Not schiz without them
- Delusions
  - Unusual false beliefs
    - Martians are controlling me
  - Reading my mind
  - Thought insertion
    - “I killed someone”
  - Behavior controlled by
    - People on TV or movies
    - Special messages
    - Magnetic waves
    - Aliens
  - Believe you are someone else
    - Often historical person
  - Someone out to get you
    - Paranoid delusions
    - Spying, plotting, cheating
- Hallucinations
  - False sensory experiences
    - See things not there
      - See invisible objects or people
    - Hear voices not there
      - Voices are most common
      - Hear multiple voices
      - Talk to invisible person
      - Voices talk to each other
    - Feel invisible fingers touching
    - Smells
- Thought disorders
  - 1. Disorganized thinking
    - organizing thoughts
    - connecting thoughts
    - garbled talk
  - 2. Thought blocking
    - Stop in middle of thought
    - Feel thought taken out head
  - 3. Nonsense words
    - Neologisms = new words
    - Disorganized speech
      - Rambling sentences
      - Incoherent patterns
- Movement disorders
  - Agitated movements
  - Repeat motions over and over
  - Catatonic = immobility
  - Rare—treated with drugs
Negative symptoms
- Occur in other disorders
- Flat affect
  - face immobile
  - monotonous voice
- Similar to brain damage
  - poor control of eye movements
  - unusual facial expressions
- Negative = lack of
  - Lack of pleasure
  - Lack initiative & planning
  - Poor hygiene
  - Lack of persistence
  - Social withdrawal
  - Poverty of speech
    - Lacks fluidity of speech
    - Words don’t flow
  - Don’t talk much
    - Even when forced
Cognitive symptoms
- Difficult to notice
- Executive functioning
- Trouble switching tasks
- Trouble paying attention
- Trouble with working memory
- Disturbed emotions
  - Hyperemotional
  - Depressed
  - Flat affect (no emotion)
Abnormalities of perception
- Schizophrenic Art
  - No foreground-background diff
  - Obsessed with certain objects (skulls)
  - Emotionally distant
  - Dark silhouettes
  - Watchful eyes
  - Fragments
  - Characteristic of LSD
Types of Schizophrenia
- 1. Disorganized
  - “Hebephrenic schizophrenia”
  - Inappropriate thoughts & behavior
  - Don’t make sense
  - Severe
  - Can’t do routine daily activities
    - bathing & meal prep
  - Hard to understand what say
  - Frustration, agitation, anger
- 2. Catatonic
  - Extremes
  - Coma-like daze
  - or
  - Talk in bizarre-hyperactive way
  - May last month+
  - Easily treated with drugs
  - Can be caused by non-schiz
- 3. Paranoid
  - Delusions
    - Someone trying to harm you
    - Hear voices plotting
  - Not as many memory problems
  - Okay concentration
  - Handle daily life okay
  - Suicide risk
- 4. Undifferentiated
  - Not meet all criteria
  - Miscellaneous
  - Junk term
Causes of Schizophrenia
- Genetics
  - Heritability
    - Runs in families
  - Environmental trigger?
  - Old egg-sperm theory
    - Older parents more schiz children
  - Children of schiz patients
    - Less than ½ become schiz
  - Inherit susceptibility to environmental factors?
    - People without family history can develop schizophrenia
Why likely genetic component
- Men & women about equal
  - Men slightly more
  - Men have earlier onset
  - Men have more severity
- About 1% worldwide
Runs in families
- 1% in general population
- 10% when parent or sibling
- 15% in fraternal twin
- 50% when identical twin
Pure genetic effect = 100%
- greatest environmental similarity
- monozygote
Adopted Children
- 12.5% siblings in same environ.
- None adopted had schiz
Correlated factors
- Women with schizophrenia
- drink & smoke during preg?
Not one single gene
- 10+ genes are more common in schizophrenics
- DISC1 gene
  - (disrupted in schizophrenia 1)
  - Controls production of dendritic spines
  - Controls generation of new neurons in hippocampus
- Other genes linked to
  - brain development
  - glutamate synapses
  - hippocampus & prefrontal cortex connections
- Combo
Dopamine hypothesis
- Over-activity of DA synapses
- In mesolimbic pathway?
- DA agonists-antagonist effects
- All treatment drugs block DA receptors
- Chlorpromazine
  - Originally used to prevent surgical shock
  - Dramatically effective
  - Reduces symptoms of schizophrenia
- DA agonists cause schiz sympts
  - Cocaine
  - Amphetamine
  - L-DOPA
  - Elation, euphoria
  - Similar to start schiz. episode
- Paranoid delusions
  - Maybe caused by increased DA input to amygdala
    - involved with emotional responses for aversive events
  - Clozapine
    - atypical antipsychotic drug
    - blocks D4 receptors
    - in nucleus accumbens
      - Part of the reward circuit
- Caused by excess activity at some dopamine synapses
  - Evidenced by
    - Drugs that help
    - Drugs that aggravate
  - Aggravaters
    - Cocaine
    - Amphetamine
    - LSD
    - Dopamine not cleaned up?
    - Schiz have twice as many D2 receptors occupied by dopamine as normal
- Dopamine not sole cause
  - Drugs that block dopamine receptors
    - do so immediately
  - but effects on behavior build up
    - gradually over 2 or 3 weeks
Glutamate Hypothesis
- Caused by poor glutamate functioning
  - dopamine inhibits glutamate
- Mixed evidence
  - Release less glutamate
    - in prefrontal cortex & hippocampus
    - have fewer glutamate receptors
  - Phencyclidine (PCP)
    - blocks NMDA glutamate receptors
    - produces symptoms similar to schiz
    - induces both negative and positive symptoms
  - Doesn’t produce psychosis in preadolescents
    - produces more severe symptoms than schiz
- Risky to increase glutamate
  - Too widely used
  - Don’t stimulate directly
  - Working on glycine
    - amino acid
    - enhances NMDA effects
    - not effective antipsychotic
    - increases antipsychotics effects
Brain Abnormalities
- MRI & CT studies
  - Found loss of brain tissue in patients with schizophrenia
- Ventricles
  - Relative size of lateral ventricles
  - 2+ size of control subjects
- Mild Brain Abnormalities
  - Less than average gray matter
  - Larger than average ventricles
  - Smaller thalamus
  - Left hemisphere slightly larger
- Worst in
  - Left temporal lobe & frontal lobe
    - Immature or poorly developed
    - dorsolateral prefrontal cortex
  - Deficits in memory & attention
  - Smaller cell bodies
    - in frontal cortex & hippocampus
  - Environmental Causes
    - Famine during pregnancy
      - (especially thiamine deficiency)
Predictors
- More likely if mother underweight
- More likely if low birth-weight
- More likely if Rh incompatible
Nneurodevelopmental hypothesis
- Schiz caused by abnormalities to nervous system during prenatal or neonatal periods
- Prenatal and Neonatal
  - Mother’s nutrition
  - Premature birth
  - Low birth weight
  - Complications during delivery
  - Rh-negative & baby Rh-positive
    - may trigger immunological rejection by mother
    - hearing deficits
    - mental retardation
    - twice usual probability of schiz
    - 2%
Season-of-birth effect
- Winter, slightly greater
- Nutrition
- viral infections
  - fever and influenza
Infections
- Flu (or other viral illness)
- More likely if born during late winter and early spring
- More likely in cities than countryside
- More likely far from equator
- Decreased winter temp?
- Childhood infections
  - Such as toxoplasma gondii
    - memory disorders, hallucinations, and delusions
    - bacteria only reproduces in cats
    - more likely to have a pet cat
Diagnosis of Schizophrenia
- Confused with drug abuse
- Can’t show abuse causes schiz
- More likely to abuse drugs
  - Self medication
  - Makes treatment less effective
Prodromal = pre-symptoms
- Self-isolation
- Increased unusual thoughts
- Increased suspicions
- Family history of schiz
Self-diagnosis as bipolar
- Or something “less sever”
Drugs can help-hurt
- Some drugs make it worse
- Marijuana
- Amphetamines
- Cocaine
- Smoking
  - 3x likely addicted to nicotine
  - 90% in schiz
  - Schiz worse during withdrawal
Some drugs make it better
- Chlorpromazine (Thorazine)
  - 1st drug successful
  - Antipsychotic drugs
  - Primarily work by blocking dopamine receptors
- Phenothiazines
  - class of neuroleptic drugs
  - includes chlorpromazine
- Try several medications
  - Not all work the same for all
  - Best combination, right dose
Relapse
- Stop taking meds
- Feel better, think don’t need
- Interact with other drugs
- Interact with alcohol
Antipsychotic medications
- Available since mid-1950’s
  - Chlorpromazine (Thorazine)
  - Haloperidol (Haldol)
  - Perphenazine (Etrafon)
  - Fluphenazine (Prolixin)
- Available since mid-1990’s
  - “atypical” antipsychotics
  - Clozapine (Clozaril)
    - psychotic symptoms
    - Hallucinations; breaks with reality
    - Side effect for clozapine
  - Agranulocytosis = loss of white blood cells
  - Risperidone (Risperdal)
  - Olanzapine (Zyprexa)
  - Quetiapine (Seroquel)
  - Ziprasidone (Geodon)
  - Aripiprazole (Abilify)
  - Paliperidone (Invega)
Old & new ones about equally effective
Side effects
- Worse when start
- Last few days for most
- Dizzy when changing positions
- Blurred vision
- Drowsiness
- Rapid heartbeat
- Sensitivity to the sun
- Skin rashes
- Major weight gain
- Rigidity of joints
- Muscle spasms
- Restlessness
- Tremors
- Tardive dyskinesia
  - Caused by long term use
  - Can’t control mouth muscles
- Tremors & involuntary move
  - Caused by prolonged blocking of dopamine receptors in basal ganglia
Antipsychotic medications
- Usually in pill or liquid form
- Some are shots given monthly
New Drugs
- Atypical medications
- Mesolimbocortical system
- Where antipsychotics impact?
  - Set of neurons
  - Project from midbrain tegmentum to limbic system
  - Don’t cause movement problems
  - Less intense effects on dopamine type D2 receptors
  - Stronger effects at D4 and serotonin 5-HT2 receptors
- More effective?
  - Better with positive symptom
  - Not so much with negative
  - Don’t improve overall quality of life any better
Long-term drug treatment
- Antipsychotic drugs not cure
- Don’t fully treat condition
- Don’t work for 1/3 of patients
- Serious side effects
  - Similar symptoms to Parkinson’s disease
  - Slow movement, lack of facial expression, general weakness

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