Schizophrenia & Antipsychotics

When does schizophrenia typically manifest?

Schizophrenia typically manifests in late adolescence or early adulthood (late teens to early 30s).

What are the positive symptoms of schizophrenia?

Positive symptoms include hallucinations, delusions, and thought disorders.

What are the negative symptoms of schizophrenia?

Negative symptoms include apathy, social withdrawal, and anhedonia.

What are the cognitive symptoms of schizophrenia?

Cognitive symptoms include impaired working memory, attention deficits, and executive dysfunction.

What is the role of dopamine in the striatum in schizophrenia?

Dopamine is increased in the striatum, which is linked to the positive symptoms of schizophrenia (e.g., hallucinations, delusions).

What is the role of dopamine in the mesocortical pathway in schizophrenia?

There is a reduction in dopamine transmission in the mesocortical pathway, which is linked to cognitive symptoms (e.g., impaired working memory).

What is the dopamine hypothesis of schizophrenia?

Schizophrenia is associated with hyperactivity in the associative striatum pathway (positive symptoms) and hypoactivity in the mesocortical pathway (cognitive deficits).

What are examples of typical antipsychotics?

Examples include Haloperidol and Chlorpromazine.

What is the mechanism of action of typical antipsychotics?

Typical antipsychotics have a high affinity for dopamine D2 receptors.

What are the side effects of typical antipsychotics?

Side effects include extrapyramidal symptoms (EPS) (e.g., Parkinsonism, akathisia, dystonia, tardive dyskinesia) and hyperprolactinemia.

What are examples of atypical antipsychotics?

Examples include Clozapine, Olanzapine, and Risperidone.

What is the mechanism of action of atypical antipsychotics?

Atypical antipsychotics have a higher affinity for serotonin (5-HT2) receptors than dopamine D2 receptors.

What are the side effects of atypical antipsychotics?

Side effects include metabolic issues (e.g., weight gain, diabetes) and a lower risk of EPS compared to typical antipsychotics.

What percentage of D2 receptor occupancy is required for antipsychotic efficacy?

>65% D2 receptor occupancy is required for antipsychotic efficacy.

At what D2 receptor occupancy does the risk of hyperprolactinemia increase?

The risk of hyperprolactinemia increases at >70% D2 receptor occupancy.

At what D2 receptor occupancy does the risk of EPS increase?

The risk of EPS (e.g., Parkinsonian-like symptoms) increases at >80-85% D2 receptor occupancy.

What happens as the dose of antipsychotics increases?

As the dose increases, D2 receptor blockade increases, leading to better symptom control but also increased side effects (e.g., hyperprolactinemia, EPS).

Why are antipsychotics (D2 antagonists) not effective in patients with low dopamine levels?

Blocking D2 receptors in patients with low dopamine levels can exacerbate symptoms, as there is already insufficient dopamine activity.

What are some novel targets for schizophrenia treatment?

Novel targets include glutamate (NMDA receptor hypofunction) and GABA (alterations in GABAergic interneurons).

What are some future directions in schizophrenia treatment?

Future directions include targeting individual symptom domains, personalized medicine, and early intervention.

What are the unmet clinical needs in pharmacological schizophrenia treatment?

Unmet needs include treating cognitive and negative symptoms and reducing side effects (e.g., metabolic issues, hyperprolactinemia, EPS).

What is the key takeaway regarding dopamine dysregulation in schizophrenia?

Schizophrenia involves hyperactivity in the striatum (positive symptoms) and hypoactivity in the mesocortical pathway (cognitive deficits).

What is the key takeaway regarding D2 receptor occupancy in antipsychotic treatment?

• Back:

  • >65%: Effective for positive symptoms.

  • >70%: Increased risk of hyperprolactinemia.

  • >80-85%: Increased risk of EPS (Parkinsonian-like symptoms).

What are the key side effects of antipsychotics?

Key side effects include Parkinson-like symptoms (due to nigrostriatal pathway blockade) and hyperprolactinemia (due to tuberoinfundibular pathway blockade).