AM - Schizophrenia III Flashcards
What does the dopamine hypothesis suggest about schizophrenia?
Symptoms of schizophrenia are due to excess dopamine neurotransmission in mesolimbic and mesocortical regions of the brain.
What evidence supports the role of dopamine in schizophrenia? (4)
Drug Effects:
* Antipsychotics (e.g., Reserpine): Deplete dopamine stores, reducing psychotic symptoms. Chlorpromazine
* Dopamine Agonists (e.g., Amphetamine, L-DOPA): Increase dopamine levels, inducing or worsening psychotic symptoms.
Neurochemical Findings:
* Post-mortem studies
* PET scans
What are some key features of Chlorpromazine? (5)
- First-line antipsychotic drug
- synthesized in 1951
- Functions as a dopamine receptor antagonist.
- Many instances also prevents the release of dopamine
- Strong correlation between dopamine receptor binding affinity and antipsychotic efficacy.
Is there evidence for increased dopaminergic transmission in schizophrenia? (3)
- Dopamine release: No consistent evidence for increased dopamine release.
- D2 receptors: Post-mortem studies show increased D2 receptors (however could be due to treatment -> upregulation).
- PET scans in drug-naive patients show inconsistent results.
How could excessive dopaminergic transmission occur without an increase in dopamine receptors? (2)
- Decreased dopamine breakdown.
- Hypersensitive dopamine receptors due to genetic variation (e.g., a haplotype causing increased susceptibility).
What are some classes of first-generation (typical) antipsychotics? (5)
- Phenothiazines (e.g., Chlorpromazine).
- Thioxanthenes.
- Butyrophenones.
classes not in the lecture:
* Diphenylbutylpiperidines
* Substituted Benzamides
What are limitations/side effects of first-generation antipsychotics? (9)
- Not effective in all patients.
- Only effective against positive symptoms.
- Weight gain (acts on histamine receptors).
- Sedation (histamine antagonist).
- Postural hypotension (alpha adrenoreceptor activity).
- Atropine-like effects (affects cholinergic transmission).
- Hyperprolactinaemia.
Movement disorders:
* Acute: Parkinson-like symptoms.
* Chronic: Tardive dyskinesia.
What is tardive dyskinesia, and what are its characteristics? (4)
- A movement disorder caused by long-term use of antipsychotics.
- Involves repetitive, purposeless movements.
- Irreversible, may cause swallowing problems.
- Cause unclear: hypersensitivity to D2 receptors or prolonged receptor blockade?
What are the advantages of atypical antipsychotics over typical ones? (3)
- Less sedation
- Low incidence of movement disorders.
- More effective against negative symptoms (also improve positive symptoms).
What are examples of atypical antipsychotics? (7)
- Clozapine.
- Quetiapine.
- Olanzapine.
- Risperidone.
- Aripiprazole.
- Asenapine.
- Paliperidone.
Summary: What evidence supports the dopamine hypothesis? (5)
- Agents decreasing dopaminergic transmission are antipsychotic.
- Genetic links to dopamine function.
- Agents increasing dopaminergic transmission cause psychosis.
- First-line antipsychotics block dopamine 2 receptors.
- Strong correlation between D2 receptor binding affinity and antipsychotic efficacy.
Summary: What evidence challenges the dopamine hypothesis? (5)
- Schizophrenia may involve multiple neurotransmitter systems or inter-hemispheric communication issues.
- Individual may just be experiencing a sedative effective but not dealing with the chemical imbalance
- Dopamine handling (not release) might be the issue (e.g., impaired removal).
- No consistent evidence for increased dopamine release in schizophrenia.
- Conflicting evidence on increased D2 receptor levels.
