Neurobiology and Treatment of psychotic disorders Flashcards
1
Q
Name 4 psychotic disorders
A
- Schizophrenia
- Schizoaffective disorder (Sz + bipolar)
- Delusional disorder
- some depressive and manic illnesses
2
Q
Sz characteristics
A
- mental state that is out of touch with reality
- abnormalities of perception, thought and ideas
- profound alterations in behaviour (bizarre and disturbing alienation)
3
Q
Sz prevalence
A
- 1% of population
- No significant influence of culture, ethnicity, background, socioeconomic groups
- Increased in urban areas
4
Q
Sz classification
A
- 2 or more present for significant period of time
- delusions
- hallucinations
- disorganised speech, emotional blunting and meaningless behaviour
- negative symptoms (affective flattening)
5
Q
Causes
A
- Genetic associations - Glutamate, neurogulin-1 gene under-expression (NMDA,synaptic development and plasticity). Monoamine function - MAO-A, TH, D2, COMT gene polymorphisms (high COMT -> low DA)
- Environment - maternal viral infections/stress, cannabis
- neurodevelopment disorder - frontal hypofusion (amygdala, frontal and temporal lobes), neurodegeneration/dementia
6
Q
Structural changes
A
- decreased amygdala, whole brain mass
- reduced basal dendrites
- increased ventricles
- decreased grey matter
7
Q
Pharmalogical evidence that DA is involved in Sz
A
- DA release (amphetamine) produces Sz
- DA release only in mesolimbic, mesocotical, not nigrostriatal
- D2 agonists produce stereotyped behaviour (not D1)
- Reserpine depletes DA - controlling positive symptoms
- strong correlation D2 blocking activity and antipsychotic action
8
Q
DA Theories for Sz
A
- Sz is caused by endogenous, DA derivative, psychotogen
- Sz - overactivity of DAergic, mesolimbic pathways
- Positive symptoms - hyperDAergic in mesolimbic system (increased D2)
- Negative symptoms - hypoDAergic activity in mesocortical system (decreased D1) - decrease cognition
- Need to increase DA in mesoCORTICAL, decrease DA in mesoLIMBIC.
9
Q
Glutamate and Schiziophrenia?
A
- NMDA antagonists - psychotic symptoms
- decreased glutamate conc and receptor density in PFC
- transgenic mice with decreased NMDA receptor expression
- NMDA hypofunction enhances mesolimbic DAergic activity and reduces GABAergic striatal neuron activity
- Project to thalamus/sensory gate (GABA inhibitory) - too little glutamate, too much DA = inhibition
- decreased glutamate (negative symptoms)
10
Q
Serotonin and Schizophrenia?
A
- LSD - partial 5-HT agonist -> hallucinations
- many antipsychotics antagonise 5-HT receptors
- 5-HT activates DA pathways (5-HT2A antagonism may contribute to antipsychotic effect and reduce movement disorder side effects)
- Main current theory
11
Q
Main current theory
A
- over stimulation of mesolimbic D2 receptors
- hypoactivity of frontal cortical D1 receptors
- Reduced prefrontal glutaminergic activity
- 5HT involved
12
Q
Antipsychotic drugs (D2 antagonists)
A
- typical or atypical (reduced extrapyramidal effects)
- all antipsychotic drugs increase and then decrease activty of midbrain D2 neurons
13
Q
Typical antipsychotics
A
- Chlorpromazine - large D2, a-adrenoceptor, histamine, ACh, 5-HT and MA blockade (very sedative, many side effects)
- Thioridazine - rarely associated with movement disorders, not sedative, anticholinergic activity
- Haloperidol - less sedative, higher incidence motor disorders (no antimuscarinic)
14
Q
Shortcomings of typical antipsychotics
A
- effective against positive
- little or no effect on negative
- balance between beneficial effect on psychosis vs movement disorders
15
Q
5HT antagonism and psychosis
A
- striatum - 5HT2a antagonists increase DA release - decrease positive
- mesolimbic pathway - D2/5HT2a antagonism - decrease positive symptoms
- mesocortical - 5HT2 antagonism: increase DA, improve negative symptoms of Sz
