Genetics of Schizophrenia Flashcards

1
Q

Schizophrenia ranks __th in global burden of illness

A

9

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2
Q

Schizophrenia is often co-morbid with….

A

drug dependence such as alcohol, nicotine, cannabis and cocaine as well as medical conditions such as obesity and Type 2 DM

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3
Q

Lifespan for schizophrenics is approximately

A

15 years less than general population

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4
Q

Previously thought that imbalance in _____ was cause of Schizophrenia but new findings suggest its to do with _____ and its action on ____ receptor

A

dopamine
glutamate
NMDA

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5
Q

Schizophrenia is due to both ________ and ______ risk factors however ________ is the biggest risk factor.

A

environmental
genetic
genetics

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6
Q

What are some examples of environmental risk factors?

A
  • Time/ place of birth
  • Infection e.g rubella
  • Prenatal e.g. bereavement
  • Obstetrics e.g CNS damage
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7
Q

Paternal age _____ risk. This is because of

A

increase

repeated cell devision where spermatogenesis is a main source of de novo mutations in the germline

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8
Q

What can genetics tell us about schizophrenia?

A
  • Many genes involved in conferring schizophrenia risk
  • More new mutations in people with schizophrenia
  • Most genes indicate that neuronal dysfunction and neurodevelopmental pathways are involved in schizophrenia
  • Depending on genotype, individuals can either be more or less likely to respond to certain antipsychotic drugs
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9
Q

Individuals with schizophrenia carry more new mutations that you would expect. There is a greater number of ___ and new mutations (i.e____________)…

A

rare
not present in either parent.
across the genome in Schizophrenia, both SNPS (single nucleopeptide polymorphisms) and CNV (copy number variants)

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10
Q

The same CNVs involved in Schizophrenia are also involved in

A

other neurodevelopmental disorders e.g. mental retardation, epilepsy and autism

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11
Q

What are the current models of neuronal dysfunction?

A
  • Dopamine hypothesis
  • Glutamate hypothesis
  • Immunological theory
  • Membrane hypothesis
  • Neurodevelopment hypothesis
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12
Q

Schizophrenia is the overactivity of which pathway?

A

Mesolimbic

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13
Q

In brief, Dopamine theory is that there is

A

overstimulation of dopaminergic pathways in the limbic and cortical areas

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14
Q

In brief, Glutamate hypothesis is that there is

A

NMDA receptor hypofunction

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15
Q

What is the dopamine theory? (in detail)

A

Schizophrenia is due to excessive dopamine neurotransmission
The evidence:
- Psycho-stimulant drugs (e.g amphetamine, cocaine, L-DOPA) mimic positive symptoms of schizo
- Found excessive release of dopamine from striatum in high risk psychosis patients, as well as those experiencing their first psychotic episode
- Antipsychotics block D2 receptor and thus stop psychotic events
- Dopamine receptor gene variants associated with Sz
- PROBLEM: fails to describe some of the negative symptoms

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16
Q

What is the glutamatergic hypothesis?

A

Sz is associated with reduction in glutamate activity or GABA/glutamate imbalance.
The evidence:
- Used PCP and ketamine which mimics both positive and negative symptoms
- They block the NMDA (glutamate) receptor
- Glutamatergic pathways associated with SZ
- can disrupt cognition and ability to process sensory info correctly

17
Q

What are some susceptibility genes for Sz?

A
  • COMT
  • REELIN
  • DISC 1
  • G 72
  • Dysbindin
18
Q

Immunological theory says that ______ activation or altered ________ may cause Sz

A

microglial

astrocytes

19
Q

Astrocytes: Possible altered process - Altered glycogen metabolism

A

Altered glutamate metabolism and synaptic function

20
Q

Astrocytes: Possible altered process - Altered release of neurotransmitters

A

Altered synaptic transmission

21
Q

Astrocytes: Possible altered process - Altered release of trophic factors

A

Altered synaptic functions

22
Q

Astrocytes: Possible altered process - Altered release of cytokines

A

Altered neuronal function

23
Q

Some studies show that prenatal _______ caused by influenza virus in 2nd trimester may be cause of Sz. This is due to ______ activation

A

inflammation

microglial