Please enable JavaScript.

Coggle requires JavaScript to display documents.

Schizophrenia (Schizophrenia (Symptomatology (Positive symptoms …

- - - - Thought disorder
        disorganised, irrational thinking
        difficulty arranging thoughts logically
        difficulty between plausible and absurd conclusions
        jump between associations in conversation
        meaningless words chosen for rhyme, rather than meaning
      - delusions
        persecution - plots or conspiracies against self
        grandeur - power or importance (special powers, godlike, special knowledge)
        control - being controlled, tiny radio in brain
      - Hallucinations
        most common auditory - voices (typically negative)
        olfactory - can contribute to persecutary delusions
    - - flattened affect
        
        poverty of speech
        
        lack of initiative and persistence
        
        anhedonia
        
        social withdrawal
    - - difficulty sustaining attention
        
        low psychomotor speed
        
        learning and memory issues
        
        poor abstract thinking
        
        poor problem solving
  - - - Early neurodevelopment model
        fixed lesions in early life
        lie dormant until age where
        damaged areas are used
        
        evidence
        (Walker, 1994, 1996)
        home movies of schizophrenics as children analysed
        more negative affect and abnormal movements
        (Schiffman 2004)
        blind rated Danish children videos
        less sociability & deficient psychomotor function
        
        evidence
        minor physical abnormalities (wide or narrow set eyes)
        people with schizopherenic relatives ~12%
        also with abnormalities ~31%
        
        head
        
        two or more hair whorls
        
        head circumference
        
        eyes
        
        skin fold at inner corner of eye
        
        wide (or narrow) set eyes
        
        ears
        
        low-seated
        
        asymmetrical
        
        mouth
        
        high-steeped palate
        
        furrowed tongue
        
        hands
        
        curved 5th finger
        
        single transverse crease in palm
        
        feet
        
        3rd toe longer than 2nd toe
        
        partial webbing of two middle toes
      - late neurodevelopment model
        abnormalities in synaptic pruning during adolescence
      - two-hit model
        early developmental insults to specific networks
        excessive pruning during adolescence & loss of plasticity
        
        Early
        obstetric complications
        prenatal infection
        nutritional difficency
        late
        substance abuse
        (cannabis 6x risk)
        adverse life effects
    - - ventricular englargement
        
        associated with loss of neurons
        
        reduced grey matter in:
        
        temporal lobes
        
        frontal lobes
        
        hippocampus
        
        Faulty cellular arrangement (asymmetry) in:
        
        cortex
        
        hippocampus
        
        Weinberger (1982)
        80 schiz 66 healthy
        lateral ventricles 2x size
    - - all associated with frontal lobe
        
        lower IQ
        
        attention deficits
        
        planning and information processing
        
        working memory deficits
        
        sensory motor gating
        
        antisaccade task
        
        oculolotor function
      - hypofrontality
        decreased activity
        dlPFC esp.
        attention to everything
        P50 second click not habituated
        PPI small pulse doesn't prepare for second
  - - - Evidence
        Dopamine agonists psychotomimetic
        L-DOPA, cocaine, amphetamine
        antipsychotics ameliorate effects
        CPZ DA antagonist
        since CPZ typical antipsychotics
        work on positive symptoms (although ~20-30% don't respond)
        Block D2 receptors
        dose required and D2 receptor affinity closely matched
      - more evidence
        PET experiment
        IBZM reversible antagonist - competes with DA for binding site
        displacement after amphetamine measured
        more DA actiity (IBZM displacement) in striatum associated with positive symptoms
      - issues
        only covers positive not negative symptoms
        atypical (low D2 affinity) drugs work better
        negative symptoms associated with underactivity in mesocortical DA pathway
        obverse of DA overactivity
    - - Clozapine
        first
        low affinity for D2 (higher for D3, D4 and 5HT)
        only drug which reduces suicide rate
        not widely used
        lots of side effects:
        weight gain, sedation, hypersalivation, tachycardia, hypotension, neutropenia
    - - ~50% of neurons use glutamate as neurotx
        in mammals balanced with GABA
        both neurotx influence almost every area and chemical in brain
        evidence that NMDA receptor implicated in schiz
      - NMDA receptor (4 subunits)
        ionotropic
        mutations in subunits
        evidence that mice(!) display schizopherenic symptoms with NMDA receptor subtypes selectively knocked out
      - Hypothesis
        NMDA receptor hypofunction
        
        why neg symptoms are treatment resistant
        
        onset in early adulthood
        
        why disorder has structural changes and cognitive deficits
      - Evidence
        NMDA receptor antagonists (PCP, Ketamine)
        cause positive, negative & cognitive symptom similarities
        glutamate agonists improve both +ve and -ve symptoms
      - positive symptoms
        in healthy brain, glutamate projected from PFC into VTA
        if not function, VTA doesn't get inhibitory singals from PFC
        negative symptoms
        in healthy brain, glutamtate from PFC to VTA
        overstimulate GABA interneuron
        from VTA DA projection to dlPFC and dmPFC
        disrupted in schiz
        less dopamine
  - - - microglia action is slow (?)
        peaking at adolescence
    - - 2nd peak of schiz in women 40-50yrold (menopause)
        estrogen may be protective