1
Q

How much of the population does schizophrenia affect?

A

β†’ 1%

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2
Q

What gender is affected more?

A

β†’ men are more affected

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3
Q

What are positive symptoms in schizophrenia?

A

β†’ increase in abnormal behaviour in addition to normal behaviour

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4
Q

What are negative symptoms in schizophrenia?

A

β†’ absence of normal behaviour

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5
Q

What are cognitive symptoms in schizophrenia?

A

β†’ problems with thought processes

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6
Q

What are examples of positive symptoms?

A

β†’ hallucinations
β†’ delusions
β†’ disorganised thought/speech
β†’ movement disorders

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7
Q

What are examples of negative symptoms?

A
β†’  social withdrawal
β†’  anhedonia
β†’  lack of motivation
β†’  poverty of speech 
β†’  emotional flatness
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8
Q

What are examples of cognitive symptoms?

A

β†’ impaired working memory
β†’ impaired attention
β†’ impaired comprehension

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9
Q

How long must symptoms last for?

A

β†’ 6 months

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10
Q

If an identical twin has schizophrenia what is the likelihood of the other twin having it?

A

β†’ 50%

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11
Q

What are 3 candidate genes for schizophrenia?

A

β†’ COMT
β†’ DISC1
β†’ GRM3

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12
Q

What are 4 pregnancy complications that can lead to schizophrenia?

A

β†’ low birth weight
β†’ premature birth
β†’ asphyxia
β†’ influenza

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13
Q

What are the 4 types of stress that can contribute to schizophrenia?

A

β†’ moving country
β†’ bereavement
β†’ loss of job/home/relationship
β†’ physical/emotional/sexual abuse

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14
Q

What kind of drug use can contribute?

A

β†’ cannabis
β†’ amphetamine
β†’ cocaine
β†’ LSD

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15
Q

What is the evidence for the dopamine hypothesis for schizophrenia?

A

β†’ DA is only released in mesocortical and mesolimbic not nigrostriatal
β†’ D2 agonists produce stereotyped behavior
β†’ Reserpine depletes DA and controls +ve symptoms
β†’ antagonist of the D2 receptor has antipsychotic effects
β†’ Amphetamine increases DA release in schizophrenics which makes the disease worse

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16
Q

What is the evidence against the dopamine hypothesis?

A

β†’ No change in DA receptors in drug free patients

β†’ No change in CSF HVA concentration

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17
Q

What are the 3 structural differences in schizophrenic brains?

A

β†’ brain is slightly smaller
β†’ grey matter is reduced
β†’ enlarged ventricles and smaller hippocampus

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18
Q

What are the 6 reasons that contribute to the pathophysiology of schizophrenia?

A
β†’ Dopamine hypothesis
β†’ Brain structure differences
β†’ Hypofrontality
β†’ NMDA receptor hypofunction
β†’ Oxidative Stress
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19
Q

WHat is hypofrontality?

A

β†’ Reduced blood flow to the frontal cortex β†’ reduced activity

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20
Q

What is the evidence for the glutamate hypothesis?

A

β†’ NMDA antagonists (PCP and ketamine) cause hallucinations and psychotic symptoms
β†’ Decreased glutamate receptor density in the prefrontal cortex
β†’ transgenic mice have decreased NMDA receptors and have decreased social interactions

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21
Q

What does NMDA hypofunction enhance and reduce?

A

β†’ enhances mesolimbic DAergic activity

β†’ reduces GABA striatal neuron activity

22
Q

What are the effects of Glutamate and Dopamine on GABA receptors?

A

β†’ Glutamate - excitatory

β†’ dopamine - inhibitory

23
Q

What does too little glutamate and too much dopamine cause in the brain?

A

β†’ uninhibited sensory input to limbic areas

24
Q

What is the evidence of the effect of 5-HT on schizophrenia?

A

β†’ LSD - partial 5-HT agonist causes hallucinations
β†’ many antipsychotics antagonise 5-HT receptors
β†’ 5-HT activates DA pathways

25
Q

What does 5-HT2A antagonism cause?

A

β†’ antipsychotic effect

β†’ reduce movement disorder side effects

26
Q

What is the main current theory for schizophrenia?

A

β†’ over stimulation mesolimbic of D2 receptors
β†’ Hypoactivity of frontal cortical D1 receptors
β†’ reduced pre frontal glutaminergic activity
β†’ 5-HT involved

27
Q

What are the two categories of antipsychotics?

A

β†’ typicals

β†’ atypicals

28
Q

What do typicals do?

A

β†’ antagonise D2 receptors

29
Q

What do atypicals do?

A

β†’ 5-HT2A agonists and D2 agonists

30
Q

Why are atypicals better than typicals?

A

β†’ they produce fewer side effects and are more effective at treating the negative symptoms
β†’ typicals are only effective in treating positive symptoms

31
Q

What are the effects of a D2 blockade on the nigrostriatal pathway?

A

β†’ Parkinsonian like symptoms
β†’ Dystonia
β†’ Akinesia
β†’ Tardive Dyskinesia

32
Q

What are the endocrine effects of a D2 blockade?

A

β†’ Breast swelling
β†’ Lactation
β†’ Impotence

33
Q

What are the effects of a D2 blockade on the mesocortical pathway?

A

β†’ Loss of motivation and reward pathways

β†’ sedation

34
Q

What are the effects of a D2 blockade on mesolimbic pathway?

A

β†’ Decreased hallucination and treats positive symptoms

35
Q

What other receptors do antipsychotics block other than D2?

A

β†’ Muscarinic
β†’ histamine
β†’ alpha adrenoceptos
β†’ 5-HT

36
Q

What is the effect of an alpha adrenoceptor blockade?

A

β†’ Postural hypotension
β†’ nasal congestion
β†’ hypothermia

37
Q

What is the effect of a muscarinic blockade?

A

β†’ Dry mouth
β†’ blurred vision
β†’ constipation
β†’ urinary retention

38
Q

What is the effect of blocking H1 and 5-HT?

A

β†’ H1 - sedation

β†’ 5-HT weight gain + photosensitisation

39
Q

What does prolactin do?

A

β†’ promotes milk production

40
Q

What are two schizoaffective disorders?

A

β†’ schizophrenia

β†’ bipolar

41
Q

What is the phase before the disease characterized by?

A

β†’ social isolation
β†’ interest in fringe cults
β†’ social withdrawal

42
Q

What are the 4 phases of schizophrenia?

A

β†’ prodrome - late teens/early twenties mistaken for depression and anxiety
β†’ Active acute phase - onset of positive symptoms, differentiation between what is and isn’t real is difficult
β†’ remission - returning to normality
β†’ Relapse

43
Q

What are the requirements for a schizophreniform disease?

A

β†’ positive symptoms for at least a month but under 6 months

44
Q

What are the 4 kinds of auditory hallucinations?

A

β†’ voices talking about them in 3rd person
β†’ voicew talking to them
β†’ voices giving running commentary
β†’voiced echoing thoughts

45
Q

What is a delusion?

A

β†’ a fixed belief not consistent with cultural norms

46
Q

What are the two states of behavior that schizophrenics exhibit?

A

β†’ hyperactivity - destructiveness

β†’impulsive behavior - murder

47
Q

What cognitive defects do schizophrenics have?

A

β†’Decreased responsiveness to emotional issues.
β†’Incongruous affect
β†’Expression of affect inappropriate to circumstances.

48
Q

What are negative symptoms caused by?

A

β†’ decreased dopamine activity in the mesocortical system
β†’ decrease in D1
β†’ Decrease in glutamate (NMDA)

49
Q

What are positive symptoms caused by?

A

β†’ Increased dopamine activity in the mesolimbic pathway

β†’ Increased D2

50
Q

What is the mesolimbic pathway?

A

β†’ VTA to
β†’ nucleus accumbens
β†’ amygdala
β†’ hippocampus

51
Q

What is the mesocortical pathway?

A

β†’ VTA to cortex

52
Q

What is the tuberohypophyseal pathway?

A

β†’ dopamine in anterior pituitary inhibiting the release of prolactin