What is Schizophrenia?
Mental disorder of:
- Thinking
- Feeling
- Behaviour
What are the symptoms of Schizophrenia?
- Hallucinations
- Delusions
- Difficulty Thinking
- Feeling Controlled
- Apathy
- Affective Blunting
- Unable to think deeply or speak extensively
- Social withdrawal
- Self neglect
All become prominent with age and time
What are the causes of Schizophrenia?
- Genes
- Subtle brain damage at birth
- Viral infections during pregnancy
- Childhood abuse
- Abuse of drugs
- Stressful events & family tensions - make it worse
What is the Pathology of Schizophrenia?
Grey matter loss in teens with early onset Schizo
Greatest loss - in frontal brain regions
Enlargement of lateral ventricles - suggests neuronal loss
Which neurotransmitters is Schizo related to?
Dopamine
Glutamate
5-HT
GABA
What are the 3 major Dopamine pathways in the brian?
Mesolimbic pathway
- Sensory stimuli and movement
Mesocortical pathway
- Cognitive, reward & emotional behaviour
Tubero-infundibular system
- Neuronal control of hypothalamic-pituitary system
What effect does Schizophrenia have to the dopamine pathways?
Mesolimbic pathway
- Overactive
Mesocortical pathway
- Underactive
Tubero-infundibular system
- Underactive
What drugs cause Schizo-like psychosis?
Amphetamine
D2 Agonists - Treats PD
Which drugs control the positive symptoms of schizophrenia?
Chlopromazine
Haloperidol
Reserpine
They are all Dopamine Antagonists
Clozapine - High antipsychotic activity - low affinity for D2 receptor
What role does Glutamate play in the brain?
Major excitatory neurotransmitter in brain
Found in 50% of synapses in brain
In schizo - less glutamate released in mesolimbic pathway - thus increased Dopamine activity in limbic system
What types of drugs are used to treat Schizophrenia?
Typical Neuroleptics (Antipsychotics) - first drugs to be discovered
Atypical Neuroleptics (Antipsychotics) - discovered later
Both based on Dopamine hypothesis
Both block post-synaptic D2-receptor
What are some examples of Typical Neuroleptics?
D2 Antagonists
Phenothiazines
- Chloromazine - Low potency
- Fluphenazine - High potency
- Thioridazine
Thioxanthene’s
- Flupenthixol - High potency
- Clopenthixol
Butyrophenones
- Haloperidol - High potency
Side effects:
- Increased prolactin secretion
- EPSE’s
- Risk of tardive dyskinesia - Repetitive, involuntary purposeless movements
What are some examples of Atypical Neuroleptics?
D2 + 5-HT2A antagonists ( Clozapine, Olanzapine, Risperidone)
D2/D3 Antagonists (Amisulpride) - more effective for negative Schizo
Dibenzodiazepines
- Clozapine - more effective in treating refractory cases ( imp. for blood test every 18 weeks - due to rare side effect - Leukopenia)
Diphenylbutylpiperizines
- Pimozide
Benzamines
- Sulpride
- Remoxipride
What are Extrapyramidal side effects?
Results due to chronic changes to the activity of the Nigostriatal & Mesolimbic dopamine systems
Schizo:
- Akathisia - inner restlessness
- Akinesia - impaired/loss of voluntary movement
- Dyskinesia - Abnormal voluntary movement
- Dystonia - Involuntary tightening & twisting of limb
What drugs are best to take for Schizo patients?
Atypical neuroleptics
Less side-effects
More effects
More expensive
mainly targets positive symptoms
