Schizophrenia

Question 0

How is the hippocampus altered in schizophrenia?

Answer 0

Disorganised pyramidal cell layers of the hippocampus (usually organised, allowing efficient inputs from entorhinal cortex and outputs to brain regions) leading to memory abnormalities, etc.

Question 1

What genes of the glutamatergic system are linked to schizophrenia?

Answer 1

Genes linked to NMDA function: - ErbB4 neuregulin receptor (regulates kinetic properties of NMDARs, induces NMDAR activation) - RGS4 (molecule found in PSD, inhibits mGluR5s)

Question 2

What four pathways to dopaminergic neurones project through?

Answer 2

1 - mesolimbic pathway 2 - mesocortical pathway 3 - nigrostriatal pathway 4 - tuberoinfundibular pathway

Question 3

What are thought disturbances defined as?

Answer 3

Difficulty keeping track of thoughts , thoughts drifting from one idea to another

Question 3

What prefrontal cortex structural abnormalities are associated with schizophrenia?

Answer 3

• enlargement of cerebral ventricles by ~20% - decrease in PFC volume (therefore neuronal loss - ⬇️ dendritic field and ⬇️ spine density) - decrease in cortical grey matter by ~2%

Question 4

What neurotransmitters are implicated in schizophrenia?

Answer 4

Dopamine and glutamate

Question 5

What is the “flat effect” of schizophrenia defined as?

Answer 5

A lack of emotional reactivity (i.e. no emotional ups or downs)

Question 7

What can schizophrenia symptoms be classified as?

Answer 7

1) POSITIVE symptoms - levels are above normal 2) NEGATIVE symptoms - levels are below normal

Question 8

What are the DA receptor families?

Answer 8

• D1 family (D1 + D5): postsynaptic GPCRs that ✅ adenylyl cyclase - D2 family (D2, D3 + D4): pre/post synaptic GPCRs that

Question 9

What is the evidence for a genetic cause for schizophrenia?

Answer 9

% lifetime risk of developing schizophrenia if: no/distant relative = 1-2% secondary relative = 2-6% primary relative = 6-17% monozygotic twin = 48%

Question 9

What are the brain regions involved in schizophrenia?

Answer 9

The prefrontal cortex and the hippocampus

Question 10

What is the prodromal period of schizophrenia?

Answer 10

A symptomatic period starting years before first acute schizophrenic episode occurs

Question 11

What is avolition defined as?

Answer 11

A lack of motivation

Question 12

What genes are implicated in schizophrenia?

Answer 12

• schizophrenia is a developmental disorder therefore genes linked to development are implicated, e.g. genes linked to myelination, atonal guidance and neuronal migration - genes linked to synaptic plasticity, e.g. neuregulin function (alters activity of NMDARs and AMPARs) - genes linked to DA metabolism and DA signalling, e.g. COMT (alters DA release)

Question 12

What is the dopamine hypothesis of schizophrenia? Is this hypothesis true?

Answer 12

Schizophrenia is a result of abnormalities to the DA system, i.e. an abnormal increase in central DA release There is evidence for this hypothesis, but it is too simplified to explain schizophrenia

Question 13

What can a psychotic episode be characterised by?

Answer 13

1) disturbances in reality and perception 2) impaired cognitive functioning 3) inappropriate affect

Question 16

Is there a simple genetic inheritance of schizophrenia?

Answer 16

No, there is not one gene/gene defect that causes schizophrenia

Question 17

What is the nigrostriatal DA pathway? How is this affected in schizophrenia?

Answer 17

DA neurones from the substantia nigra projecting to the dorsal striatum This is part of the extrapyramidal motor system, involved in initiation and control of movement - D2 receptors in the SN are blocked by antipsychotics, leading to a decrease in motor control and Parkinson’s symptoms

Question 18

What is alogia defined as?

Answer 18

“Poverty of speech”, i.e. a general lack of additional, unprompted contributions to normal speech

Question 19

What factors allow a schizophrenia diagnosis?

Answer 19

1 - two or more key positive/negative symptoms 2 - social/occupational dysfunction 3 - these disturbances much be continuous for at least 6 months 4 - drug abuse must be excluded

Question 19

What is the tuberoinfundibular DA pathway? How is this affected in schizophrenia?

Answer 19

DA neurones projecting to the hippocampus and anterior pituitary. Antipsychotic drugs acting on this pathway linked to unwanted milk production side effect. (DA released into the perivascular spaces here is taken up by capillaries and transported to pituitary, where it acts on cells to inhibit prolactin release and regulate milk production and lactation)

Question 20

Give four examples of positive symptoms of schizophrenia

Answer 20

Hallucinations, delusions of grandeur/persecutions, thought disturbances and bizarre behaviour

Question 21

When are symptoms of schizophrenia first seen?

Answer 21

Disease onset is ADOLESCENCE but may see PRODROMAL SYMPTOMS (early symptoms indicating disease onset before specific symptoms occur)

Question 22

What is the glutamate hypothesis of schizophrenia? What is the evidence for this hypothesis?

Answer 22

Schizophrenia linked to hypo function in the glutamatergic system.

Question 23

What is the mesocortical DA pathway? How is this affected in schizophrenia?

Answer 23

DA neurones from the VTA projecting to the neocortex and the PFC. This is HYPOACTIVE in schizophrenia.

Question 24

What are the environmental factors underlying schizophrenia?

Answer 24

Family stress, poor social interactions, poor maternal nutrition, infection at an early age, trauma at an early age (e.g. head trauma)

Question 25

Is gliosis seen in schizophrenia?

Answer 25

No - gliosis is the reactive change of glial cells in response to CNS damage, but schizophrenia is a neurodevelopment disease and not a neurodegenerative disease

Question 26

What are the prodromal symptoms of schizophrenia?

Answer 26

Increasing social withdrawal Increasing lack of attention/care for personal hygiene ETC. NB: will arise gradually and get worse over time

Question 28

Give five negative symptoms of schizophrenia

Answer 28

Social withdrawal, flat effect, anhedonia, avolition and alogia

Question 29

What are hallucinations defined as?

Answer 29

Sensory perceptions in the absence of external stimuli. Can be tactile (e.g. feeling insects on skin), olfactory, gustatory or auditory (e.g. hearing voices)

Question 31

What is anhedonia defined as?

Answer 31

An inability to experience enjoyment/pleasure from activities that would usually be found as enjoyable

Question 32

What is the mesolimbic DA pathway? How is this affected in schizophrenia?

Answer 32

DA neurones projecting from the VTA to the septum, amygdala, hippocampus, ventral striatum and frontal cortex. This is HYPERACTIVE in schizophrenia.

Question 33

Where are dopaminergic neurone cell bodies located in the brain?

Answer 33

In the ventral tegmental area (A10) and in the substantia nigra (A9)

Question 34

What are delusions defined as?

Answer 34

A belief held with complete conviction despite being based on strange, unrealistic or mistaken views