Neurobiology and Treatment of Schizophrenia

Question 1

What is the general risk of schizophrenia and what does it rise to if your monozygotic twin has it?

Answer 1

1% general risk

Rises to 50% if monozygotic twin has it

Question 2

What two factors play a role in developing schizophrenia?

Answer 2

• Genetics (polygenic so can be attributed to multiple genes)
• Environment

Question 3

What are the environmental factors at birth that can increase likelihood of developing schizophrenia?

Answer 3

• Obstetric complications
• Prenatal infection
• Nutritional deficiency

Question 4

What are the environmental factors at adolescence that can increase likelihood of developing schizophrenia?

Answer 4

• Substance abuse (e.g. cannabis)

- Adverse life events

Question 5

What is the difference in onset of schizophrenia in males and females?

Answer 5

Males tend to develop it a younger age:

Males = mid-high 20s
Females = late 20s - low 30s

Question 6

What are noticeable structural changes in the brain of people with schizophrenia?

Answer 6

• Ventricular enlargement
• Cellular changes in hippocampus and cortex
• Loss of grey matter, leading to a reduction in brain volume

Question 7

A reduction in the length of what structure has been associated with hallucinations?

Answer 7

Paracingulate sulcus

Question 8

What happens to gray matter during adolescence, and what would early-onset schizophrenia do to this?

Answer 8

During adolescence there is a loss of grey matter, and schizophrenia would increase the loss of gray matter

Question 9

What is hypofrontality and what is it associated with?

Answer 9

A decrease in blood flow to the PFC

Associated with schizophrenia

Question 10

What type of side effects can typical antipsychotics lead to?

Answer 10

Parkinsion-like side effects

Question 11

What type of neurons make up the midbrain, and what do they project onto?

Answer 11

Dopaminergic neurones

Project into the forebrain

Question 12

What are the two reasons why it is thought that dopaminergic neurons play a role in schizophrenia?

Answer 12

Because typical antipsychotics (which are D2 receptor antagonists) prevent the positive symptoms of schizophrenia

Dopamine agonists (e.g. L-DOPA and cocaine) induce positive symptoms of schizophrenia

Question 13

How can drug induced positive symptoms be managed?

Answer 13

With atypical antipsychotics since they block D2 receptors

Question 14

What protein are D1 receptors coupled with?

Answer 14

Gs protein

Question 15

What receptors are examples of D1 receptors?

Answer 15

D1 and D5

Question 16

What receptors are examples of D2 receptors?

Answer 16

D2, D3 and D4

Question 17

What protein are D2 receptors coupled with?

Answer 17

Gi protein

Question 18

What are extrapyramidal side effects (EPS) and what type of drug can cause them?

Answer 18

Drug-induced movement disorders

Caused by typical antipsychotics

Question 19

What are examples of extrapyramidal side effects and describe their cause and effects on sufferers?

Answer 19

• Parkinsonian-like symptoms which are caused by the inhibition of dopamine action in the caudate - leading to slow movement and lack of facial expressions
• Tardive dyskinesia which is unintended facial muscle movements caused by the up regulation of D2 receptors

Question 20

Do atypical antipsychotics cause EPS?

Answer 20

No

Question 21

What type of drug is clozapine and what are some of the side effects of it?

Answer 21

Atypical antipsychotic

• Weight gain
• Sedation
• Hypotension
• Tachycardia
• Hypersalivation

Question 22

What effect do atypical antipsychotics have on have on DA activity in the PFC and NAcc

Answer 22

Increase activity in the PFC

Decrease activity in the NAcc

Question 23

What type of drug is risperidone?

Answer 23

Atypical antipsychotic

Question 24

What is phenylcyclidine (PCP / Angel Dust) and why does it cause the +ve, -ve and cognitive symptoms of schizophrenia?

Answer 24

Glutamate antagonist

Leads to less glutamatergic firing and so less glutamate. This can then lead to hypofrontality.