Neurobiology of Psychosis

Question 1

What is the % heritability of psychosis?

Answer 1

78%

Question 2

What is the lifetime risk of Schizophrenia if your parents/MZ twin display it?

Answer 2

Parents and MZ twin: 45%

Question 3

By how much is the risk of schizophrenia increased by childhood viral infection?

Answer 3

50%

Question 4

What will you see on imaging in patients with a poor schizophrenic prognosis?

Answer 4

Reduced frontal lobe volume
Reduced frontal lobe grey matter
Enlarged lateral ventricle volume

Question 5

What are the key features of grey matter abnormalities in schizophrenia?

Answer 5

Schizophrenia associated with widely distributed GM abnormalities
Abnormalities are present early in illness and likely pre-morbidly
Grey matter reductions due to reduced arborisation and not neuron loss
Grey matter reductions likely progressive in the initial years of illness

Question 6

What is found in diffusion tensor imaging in schizophrenic patients?

Answer 6

Fractional anisotrophy (healthy white matter tracts decreased)
Mean diffusivity (less health WM tracts) increased
But increased FA correlates with psychotic symptom severity

Question 7

What is the neurodevelopment model in schizophrenia?

Answer 7

Environmental risk factors act in utero
Children who later develop schizophrenia have identifiable impaired behaviour, motor and intellectual development from infancy
Ventricular enlargement is present at diagnosis and is non-progressive
Disruption of normal cerebral cortical cytoarchitecture - in entorhinal cortex
No gliosis

Question 8

Schizophrenia is related to the overactivity of what pathways?

Answer 8

Dopamine

Question 9

What does the D1 receptor family do (D1 and D5)?

Answer 9

Stimulate cAMP

Question 10

What does the D2 receptor family do (D2,3 and D4)?

Answer 10

Inhibit adenylyl cyclase
Inhibit voltage-activated Ca2+ channels
Open K+ channels

Question 11

What is the agonist of D2?

Answer 11

Bromocriptine

Question 12

What is the antagonist of D2?

Answer 12

Raclopride

Haloperidol

Question 13

What is the agonist of D3?

Answer 13

Quinpirole

7OH-DPAT

Question 14

What is the antagonist of D3?

Answer 14

Raclopride

Question 15

What is the antagonist of D4?

Answer 15

Clozapine

Question 16

Within what brain regions is D1 located?

Answer 16

Neostriatum
Cerebral cortex
Olfactory tubercle
Nucleus accumbens

Question 17

Within what brain regions is D2 located?

Answer 17

Neostriatum
Olfactory tubercle
Nucleus accumbens

Question 18

Within what brain regions is D3 located?

Answer 18

Nucleus accumbens

Island of Calleja

Question 19

Within what brain regions is D4 located?

Answer 19

Midbrain

Amygdala

Question 20

Within what brain regions is D5 located?

Answer 20

Hippocampus

Hypothalamus

Question 21

Where are D1 and D2 both located in?

Answer 21

Limbic and striatal areas. Other subtypes small number but more discrete distribution

Question 22

What does subcortical dopamine hyperactivity lead to?

Answer 22

Psychosis

Question 23

What does mesocortical dopamine hypoactivity lead to?

Answer 23

Negative and cognitive symptoms

Question 24

What proteins cause the brain pathology in schizophrenia?

Answer 24

Neuregulin
Dysbindin
DISC-1

Question 25

What is neuregulin?

Answer 25

A signalling protein that mediates cell-cell interactions and plays critical roles in the growth and development of multiple organ systems

Question 26

What is dysbindin essential for?

Answer 26

Adaptive neural plasticity

Question 27

What is DISC-1 involved in?

Answer 27

Neurite outgrowth and cortical development through its interaction with other proteins

Question 28

What are the typical antipsychotics?

Answer 28

``` Chlorpromazine Thioridazine Fluphenazine Haloperidol Zuclopentixol ```

Question 29

What defines an atypical antipsychotic?

Answer 29

Less likely to induce Extra-Pyramidal side-effects High 5-HT2A to D2 ratio Better efficacy against negative symptoms Effective in patients unresponsive to typical drugs

Question 30

What are the atypical psychotics?

Answer 30

``` Olanzapine Risperidone Quetiapine Clozapine Aripiprazole Amisulpride ```

Question 31

What do psychotomimetic drugs with high affinity for 5-HT2 receptors cause?

Answer 31

Hallucinations and thought disturbance- leads to evidence of reduced receptor binding in people at risk of schizophrenia

Question 32

What is a severe adverse effect of clozapine?

Answer 32

Agranulocytosis

Question 33

When should an FBC be carried out in patients on clozapine?

Answer 33

Weekly for first 6 months Fortnightly for next 6 Every 4 weeks thereafter For 1 month after clozapine cessation