Schizophrenia

Question 1

What are the symptoms of schizophrenia?

Answer 1

Positive symptoms: disordered thoughts, delusions, and hallucinations
Negative symptoms: Absence of emotion or emotional flatness. Loss of motivation, social interaction
Cognitive Deficits: executive function & working memory

Question 2

What are the anatomical defects in schizophrenia?

Answer 2

Accelerated loss of cortical gray matter and enlarged lateral ventricles. Loss of grey matter is due to loss of dendrites, but neuronal numbers remain the same. Also see decreased spine density

Question 3

What are the synaptic changes in schizophrenia?

Answer 3

Reduced synapse number due to developmental over-pruning in schizophrenia.

Question 4

What is the dopamine hypothesis for schizophrenia?

Answer 4

There is altered dopamine release from presynaptic terminals, but no change in D2 receptor number or transporters.

Question 5

What is the evidence for the dopamine hypothesis?

Answer 5

1. Blocking D2 receptors inhibits psychosis
2. Activation of D2 receptors causes psychotic behavior
3. Increased incidence of schizophrenia in individuals with a mutation in COMT gene

Question 6

What is the glutamate hypothesis of Schizophrenia?

Answer 6

Over-pruning of spines during development may cause glutamate hypofunction which leads to enhanced dopamine release.

Question 7

What is the evidence for the glutamate hypothesis?

Answer 7

1. PCP and ketamine mimic psychosis
2. In animals a loss of NMDAR causes schizophrenia-like symptoms
3. Reduced number of spines leads to loss of NMDAR

Question 8

What is the GABA hypothesis in Schizophrenia?

Answer 8

Reduced GABA leads to an impaired E/I balance in DLPFC.

Question 9

What is the evidence for the GABA hypothesis?

Answer 9

1. Reduced GABA synthesized
2. cells in DLPFC have smaller cell bodies & fewer dendrites so fewer GABA receptors
3. Shortened GABA responses
4. Excitatory GABA

Question 10

What are gamma oscillations?

Answer 10

Result from rhythmic interactions between excitatory neurons and GABAergic neurons in the cortex. The amplitude of gamma oscillations are involved with parallel narratives where memories are being bound and organized together.

Question 11

What happens to gamma oscillations in schizophrenia?

Answer 11

The amplitude of gamma oscillations is reduced, due to a change in the E/I balance. This leads to a deficit in binding the various elements that form the narrative of a cognitive task.

Question 12

What happens with the relationship between dopamine and “motivational salience” in schizophrenia?

Answer 12

When there is too much dopamine, the wrong importance is attached to stimuli so this results in confusion of external versus internal sources (ex. hearing voices)

Question 13

What is the acetyl choline hypothesis?

Answer 13

The reason why most SZ patients smoke is because Alpha7 subunit of nAChR reduced in SZ which affects cognition

Question 14

What are the candidate genes for schizophrenia?

Answer 14

1. DISC1
2. COMT
3. NRG-1
4. Neurexins
5. Hemizygous deletion on c22q.11.2

Question 15

What are the white matter changes in SZ?

Answer 15

Overall reduction in white matter volume, oligodendrocytes are reduced in frontal lobe, & both fornix and cingulum are reduced

Question 16

What are the treatments for schizophrenia?

Answer 16

1. Anti-psychotic drugs are D2 antagonists