When is the onset of schizophrenia?
Adolescence & young adulthood
There is a 'spectrum of symptoms' for schizophrenia. What does this divide the symptoms into?
• Positive symptoms
• Negative symptoms
What are the 'positive' symptoms of schizophrenia?
• Disorders of thought
What are the 'negative' symptoms of schizophrenia?
• Blunted emotions
• Social withdrawal
What is the importance of positive and negative symptoms?
They respond differently to different medications.
What brain differences are seen in those with schizophrenia?
• Developmental abnormalities in the limbic system
• Smaller temporal lobes
• Enlarged ventricles
Describe a theory of schizophrenia.
Dopamine theory of Schizophrenia: "Schizophrenia is caused by overactive MESOLIMBIC AND MESOCORTICAL dopamine systemS in the brain"
What are the three main dopamine systems in the brain?
Where does the tuberoinfundubular pathway run from and to? What does dopamine do at the destination?
Hypothalamus --> pituitary stalk Dopamine acts tonically as prolactin release inhibiting factor (PRIF)
Outline prolactin regulation
• Hypothalamic nuclei release prolactin releasing factor (PRF)
• PRF Stimulates anterior pituitary to release prolacin
• Dopamine from tuberoinfundibular tract inhibits anterior pituitary prolactin release
What does prolactin do?
Stimulates milk production and differentiation of mammary tissue
Where is prolactin released from?
What is released from the posterior pituitary?
Where does the nigrostriatal pathway run from and to? What does dopamine do at the destination?
substantia nigra --> dorsal striatum Involved in the initiation and control of movement (extrapyramidal pathway of movement)
What are the diseases of the nigrostriatal pathway?
• Parkinson's disease
• Huntington's chorea
What is the relevance of the nigrostriatal pathway with schizophrenia?
No direct relationship, but the drugs used to treat schizophrenia have side effects which affect this pathway
Where does the mesolimbic pathway run from and to? What does dopamine do at the destination?
Ventral tegmentum --> Ventral striatum & hippocampus Reward, addiction, sensory processing
Where does the mesocortical pathway run from and to? What does dopamine do at the destination?
Ventral tegmentum --> frontal cortex Cognition, mood
What causes dopamine imbalance in schizophrenia?
Increased synthesis of dopamine
How do antipsychotic drugs work?
They block D2 receptors in limbic and cortical areas
What were the first antipsychotic drug classes to be high-affinity D2 receptor antagonists? What are the side effects of this and why?
Phenothiazines and thioxanthenes Have tri-cyclic structures (like TCAs but arent) which means its not selective, and has affinity for many receptors:
• Weight gain
• Dry mouth
• Blurred vision
• Urinary retention
• Postural hypotension
• Extrapyrimidal side effects
NB: D2 for mesocortical and mesolimbic pathways is the therapeutic target
Antipsychotics which are specific to D2 receptors may still cause side effects. What are these? Why does this occur?
• Extrapyrimidal side effects
What does 'tardive' mean in tardive dyskinesia?
Tardive, because it begins 6 months after initiation of treatment
Is tardive dyskinesia permanent?
What are the extrapyramidal side effects?
• Parkinson's symptoms (rigidity, tremor, etc)
• Tardive dyskinesia (repetitive involuntary movement)
What are the side effect profiles of phenothiazines and thioxanthenes?
Group I: Sedation (H1)
Group II: Anticholinergic (M1)
Group III: Extrapyrimidal (D2)
What drug class ditched the tricyclic structure, and were more selective for just D2 receptors? Give an example.
What are the side effects of butyrophenones?
Extrapyramidal side effects remain
Prolactin side effect remain (galactorrhea and gynaecomastia)
Summarise the 1st generation antipsychotic classes and an example of each
What are 2nd generation antipsychotics also known as?