Schizophrenia Overview and Symptoms

Study Notes

A mental disorder caused by dysfunction in the brain
Affects young people and is often chronic and disabling
The main neurotransmitters involved in the pathogenesis of schizophrenia are dopamine and serotonin
Evidence suggests an overactivity of dopamine in the mesolimbic and mesocortical pathway of the brain

Positive Symptoms:
- Delusions (often paranoid)
- Hallucinations (often auditory, exhortatory)
- Thought disorder (wild trains of thought)
- Abnormal, disorganized behavior (stereotyped movements, disorientation, aggression)
- Catatonia (immobility or purposeless activity)
Negative Symptoms:
- Social withdrawal
- Flattening of emotional responses
- Anhedonia (inability to experience pleasure)
- Cognitive impairment
- Reluctance to perform daily tasks

Used in Western medicine for over 50 years
Chlorpromazine and risperidone were the first drugs to be effective against schizophrenia
First generation antipsychotics, or typical antipsychotics, were discovered in the 1950s
Second generation antipsychotics, or atypical antipsychotics, were discovered in the 1960s and introduced clinically in the 1970s

Neuroleptic drugs or major tranquilizers
Reduce psychotic symptoms in various conditions, including schizophrenia, bipolar disorder, psychotic depression, senile psychoses, and drug-induced psychoses
Not curative and cannot eliminate the underlying thought disorder, but they reduce the intensity of symptoms and allow patients to function in a supportive environment

Typical Antipsychotics (1st generation):
- High affinity for dopamine receptors
- Increased risk of extrapyramidal side effects
- Effective against positive symptoms
Atypical Antipsychotics (2nd generation):
- High affinity for serotonin, dopamine, and other receptors
- Less likely to cause extrapyramidal side effects
- Effective against both positive and negative symptoms

Synthesis of dopamine involves conversion of tyrosine to dopa (rate-limiting step), followed by decarboxylation to form dopamine
Dopaminergic neurons lack dopamine hydroxylase and cannot convert dopamine to norepinephrine
Dopamine Receptor Types:
- D1 & D5: Gs coupled, stimulate adenylyl cyclase
- D2, D3, and D4: Gi coupled, inhibit adenylyl cyclase and activate potassium channels

Mesolimbic & Mesocortical Pathways:
- Cell bodies in the brain project to the limbic system and cortex, respectively
- Involved in reward, motivation, and cognition
Nigrostriatal Pathway:
- Cell bodies in the substantia nigra project to the striatum
- Responsible for motor control
Tuberoinfundibular Pathway:
- Cell bodies in the hypothalamus project to the pituitary gland
- Regulates prolactin secretion

Typical Antipsychotics:
- Block dopamine receptors, primarily D2 receptors in the mesolimbic pathway
- Reduction in dopamine activity in this pathway helps to reduce positive symptoms
Atypical Antipsychotics:
- Block dopamine receptors (D2) and serotonin receptors (5-HT2A)
- Have higher affinity for serotonin receptors than dopamine receptors
- May also affect other neurotransmitter systems, such as glutamate and acetylcholine
- May help to improve both positive and negative symptoms and reduce cognitive impairment

Typical Antipsychotics:
- Extrapyramidal Side Effects (EPS):
  - Acute dystonia (muscle spasms)
  - Akathisia (restlessness)
  - Parkinsonism (tremors, rigidity)
  - Tardive dyskinesia (involuntary movements)
- Neuroleptic Malignant Syndrome (NMS):
  - Rigidity, fever, altered consciousness, and autonomic instability
Atypical Antipsychotics:
- Metabolic syndrome:
  - Weight gain, hyperglycemia, dyslipidemia
- Prolactin elevation:
  - Gynecomastia (breast development in males), galactorrhea (breast milk production)
- EPS:
  - Typically milder than with typical antipsychotics

Antipsychotic drugs are powerful medications and should only be used under the supervision of a qualified medical professional
Not all patients respond to antipsychotic medications in the same way, and dosages need to be adjusted on an individual basis.