Overview of Psychotic Symptoms and Schizophrenia

Introduction

• Focus on dopamine hypothesis related to psychosis and schizophrenia.
• Understand key aspects of dopamine neurotransmission, receptors, and brain circuits.

What is Psychosis?

• A syndrome consisting of delusions and hallucinations.
• Delusions: Fixed, often bizarre beliefs resistant to counter-arguments.
• Hallucinations: Sensory experiences without external stimuli; auditory is most common.
• Other Symptoms: Disorganized speech, behavior, impaired reality testing, negative symptoms like diminished emotional expression.

Schizophrenia as a Prototype

• Positive symptoms: Delusions, hallucinations, disorganized speech/behavior.
• Negative symptoms: Apathy, anhedonia, cognitive blunting.
• Symptom Domains: Affected by different brain circuits.
  • Positive symptoms: Mesolimbic area.
  • Negative symptoms: Mesocortical and prefrontal cortex.

Dopamine Hypothesis

• Traditional focus on dopamine, particularly excess at D2 receptors in the mesolimbic pathway.
• New insights into involvement of glutamate and serotonin networks.

Dopamine Pathways

1. Mesolimbic Pathway

• Associated with reward, motivation, emotion regulation.
• Excess dopamine: Linked to positive symptoms of schizophrenia.

2. Mesocortical Pathway

• Projects to prefrontal cortex, linked to cognition and emotion regulation.
• Deficiency: Linked to cognitive and negative symptoms of schizophrenia.

3. Nigrostriatal Pathway

• Regulates motor movements.
• Dysregulation: Causes motor-related symptoms when treated.

4. Tuberoinfundibular Pathway

• Dopamine regulates prolactin secretion.
• Impact of Antipsychotics: Can cause elevated prolactin levels leading to side effects.

Dopamine Synthesis and Metabolism

• Begins with tyrosine intake from diet, converted into dopamine via enzymes.
• Dopamine stored in vesicles, released during neurotransmission.
• Handled via reuptake, breakdown by enzymes (COMT, MAOA, MAOB), or false substrate transport.

Dopamine Receptors

• Divided into D1-like (D1, D5) and D2-like (D2, D3, D4).
• Postsynaptic: Found in all five pharmacological subtypes.
• Presynaptic (Autoreceptors): D2, D3 regulate dopamine release.

Clinical Implications

• Understanding dopamine pathways aids in conceptualizing treatments and side effects in schizophrenia.
• Medications affect multiple pathways; selective targeting remains a challenge.

Conclusion

• Dopamine Hypothesis: Central but evolving theory in understanding schizophrenia and psychosis.
• New evidence suggests involvement of associative striatum in emotional regulation, expanding beyond classic dopamine pathways.