Schizophrenia and antipsychotics

Question 1

What is the meaning of schizophrenia?

Answer 1

Literally - divided mind. It is not multiple/split personalities, but the division between internal thought and external reality.

Question 2

What is the definition of schizophrenia?

Answer 2

It is a long-term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour which leads to a faulty perception, inappropriate actions and feelings, withdrawel from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation.

Question 3

What were the early ideas about psychosis?

Answer 3

That it is a developed mental disorder and that it was progressive from mania, paranoia to hallucinations etc.

Question 4

What is the problem of diagnosis with schizophrenia?

Answer 4

There is no reliable, consistent or useful body fluid biomarker so it is diagnosed through clinical observation and history.

Question 5

What are some of the symptoms of schizophrenia?

Answer 5

Delusions, hallucinations, disorganised speech/behaviour, affecting flattening, alogia (inability to speak) or avolition (inability to accomplish tasks).

Question 6

What is the prevalence of schizophrenia?

Answer 6

Around 1%.

Question 7

What is the median age of onset of schizophrenia for men and women?

Answer 7

26 for men, 29 for women.

Question 8

What are the causes of schizophrenia?

Answer 8

Genetic, environmental and structural brain changes.

Question 9

What are some environmental factors that contribute to the development of schizophrenia?

Answer 9

Pregnancy and delivery complications, prenatal and childhood virus infection, urban birth and residence, psychosocial factors.

Question 10

What are some of the structural brain changes that can contribute to the development of schizophrenia?

Answer 10

Developmental disruption of neuronal migration, enlarged vesicles, reduced regional cerebral volumes, loss of neurones and reduced network and functional activity.

Question 11

What is the trend with hospitalisations due to schizophrenia with men and women?

Answer 11

More men are hospitalised at a younger age, whereas more females are hospitalised at an older age.

Question 12

What is the risk of developing schizophrenia in a monozygotic twin if the other twin has schizophrenia?

Answer 12

50%.

Question 13

How do ventricles in the brain differ between normal subjects and a schizophrenic?

Answer 13

The ventricles are much larger - this is the space in the brain, mostly likely to due the loss of brain tissue.

Question 14

How are cocaine and amphetamine liked to psychosis?

Answer 14

They release dopamine and chronic abuse can cause toxic psychosis such as paranoid delusions, hallucinations and compulsive behaviour.

Question 15

What is L-DOPA?

Answer 15

The precursor to dopamine.

Question 16

What is the action of antipsychotic drugs?

Answer 16

Blocking the D2/DA receptor.

Question 17

What is a gene that is a risk factor in developing schizophrenia?

Answer 17

The D2 DA gene. It is thought that DA receptors may be increased in schizophrenics.

Question 18

What are the drugs used to treat schizophrenia?

Answer 18

High affinity D2 receptor agonists.

Question 19

What are first gen antipsychotics used for schizophrenia effective against?

Answer 19

Positive symptoms - hallucinations, delusions, motor disorders rather than avolition, anhedonia, povery of speech, social withdrawel etc.

Question 20

What are some of the side effects of antipsychotics that are DA related?

Answer 20

Early-Parkinson’s like symptoms, late huntingdon’s-like symptoms and sexual dysfunction due to increased prolactin release.

Question 21

What are some side effects of antipsychotics that are non-DA related?

Answer 21

Sedation, hypotension and peripheral autonomic side effects - blurred vision, dry mouth, constipation.

Question 22

What are second gen antipsychotics for schizophrenia effective against?

Answer 22

Both positive and negative symptoms, they have a low affinity for D2 receptors and a high affinity at 5HT2.

Question 23

What are the side effects of second gen antipsychotics?

Answer 23

They have less motor side effects than first gen, but other side effects such as weight gain and diabetes.

Question 24

What is an alternative to antipsychotics that target dopamine receptors?

Answer 24

Those that target 5HT instead.

Question 25

What are problems with dopamine receptor targeting antipsychotics?

Answer 25

There are serious dopaminergic side effects, many neuroleptics only control positive symptoms, the drugs may block other receptors such as muscarinic.

Question 26

What is the role of 5HT in schizophrenics?

Answer 26

Increased levels of 5HT in schizophrenics.

Question 27

What does LSD do?

Answer 27

It is a 5HT agonist that induces hallucinations, cognitive impairment and agression.

Question 28

What is the affinity of typical antipsychotics?

Answer 28

High affinity for D2 receptors. This means the 5HT2a receptor is strongly activated, causing reduced dopamine release. All D2 receptors are blocked.

Question 29

What is the affinity of an atypical antipsychotic?

Answer 29

Low affinity for D2 and high affinity for 5HT2a. This means dopamine release is not blocked and only some D2 receptors are blocked, resulting in reduced motor side effects.

Question 30

What does the 5HT2a receptor do?

Answer 30

It causes reduced dopamine release.

Question 31

What is the potency of antipsychotic drugs related to?

Answer 31

The ability of each of the drugs to bind to the dopamine D2 receptor in the brain tissue.

Question 32

What causes side effects of antipsychotics?

Answer 32

The blocking of the D2 receptor.

Question 33

What symptoms to high affinity D2 agonists treat?

Answer 33

Only positive symptoms - not negative.

Question 34

What are some of the dopamine-related side effects of first gen. antipsychotics?

Answer 34

Pseudoparkinsonism, tardive dyskinesia, motor effects, increased prolactin release resulting in sexual dysfunction.

Question 35

What are some of the non-dopamine related side effects of first gen. antipsychotics?

Answer 35

Sedation, hypotension and peripheral autonomic symptoms.

Question 36

Why is the dopamine block immediate but the clinical effects take weeks to occur?

Answer 36

There may be other changes to dopamine systems and other systems that are effected by the dopamine pathways.

Question 37

What is the difference between first gen antipsychotics and second gen?

Answer 37

First gen block lots of D2 receptors, whereas second gen block 5HT2a receptors (which causes more dopamine to be released as the 5HT2a receptors reduce dopamine release) and partially block D2 receptors.

Question 38

What is the benefit of second gen antipsychotics?

Answer 38

As less D2 receptors are being blocked, there are less of the negative side effects associated.

Question 39

What is disordered migration?

Answer 39

Where glutamate neurons migrate to where they shouldn’t be in early development.

Question 40

How is disordered migration potentially linked to schizophrenia?

Answer 40

These glutamate systems may no longer be functioning correctly, potentially having an effect on schizophrenia.

Question 41

What pathways are involved in the positive symptoms of schizophrenia?

Answer 41

The mesolimbic dopamine pathway may be dysfunctional.

Question 42

How is the glutamate neurone involved in dopamine release?

Answer 42

The glutamate neurone excites the inhibitory neurone that inhibits that GABA neurone/dopamine neurone.

Question 43

WHat symptoms is the mesolimbic pathway associated with?

Answer 43

Positive symptoms

Question 44

What symptoms is the mesocortical pathway associated with?

Answer 44

Negative symptoms.

Question 45

What is the case in the mesocortical system that causes negative symptoms?

Answer 45

Loss of excitation reducing dopamine release.