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Neurology > Schizophrenia > Flashcards

Schizophrenia Flashcards

1
Q

What is a psychotic disorder?

A

Major psychoses (‘madness - cancer of mental illness’)

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2
Q

Name examples of psychotic disorders

A
  • Schizophrenia
  • Schizoaffective disorder = schizophrenia and bipolar
    disorder
  • Delusional disorder
  • Some depressive and manic illnesses
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3
Q

Why is schizophrenia the most important psychotic disorder?

A

Early in onset
Prevalent ~1%
Disabling and chronic

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4
Q

Describe the characteristics of schizophrenia

A

Mental state that is out of touch with reality
Abnormalities of perception, thought & ideas

Profound alterations in behaviour (bizarre and disturbing alienation)

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5
Q

Outline the prevalence of schizophrenia

A

Affects up to 1% of the population
No significant influence of culture, ethnicity, background, socioeconomic groups
Increased in urban areas

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6
Q

How does gender influence schizophrenia

A

No difference between sexes:

Men: 15-25yrs (poorer response to therapy)

Women: 20-30yrs

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7
Q

What are the 4 phases of schizophrenia?

A
  1. Prodome
  2. Active/Acute phase
  3. Remission
  4. Relapse
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8
Q

Describe the prodome phase

A

The Prodrome (wks - yrs)

Early onset of symptoms in late teens/early twenties: often mistaken for depression or anxiety

Can be triggered by stress

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9
Q

What occurs during the active phase of schizophrenia?

A

The Active/Acute Phase (4-6wks SCZ diagnosed)

Onset of positive symptoms (hallucinations/delusions)

Differentiation of what is and isn’t real becomes difficult

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10
Q

What is remission?

A

Remission when treatment 🡪 return to ‘normality’

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11
Q

What happens in relapse?

A

Cycles between remission and relapse common – patients can tell when relapse is coming

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12
Q

What is schizophreniform?

A

Schizophreniform disorder is a type of psychotic illness with symptoms similar to those of schizophrenia, but lasting for less than 6 months.

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13
Q

What are the 3 classes of schizophrenia symptoms?

A
  • Positive
  • Negative
  • Cognitive
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14
Q

What are the positive symptoms of schizophrenia

A
  • Hallucinations (visual/auditory)
  • Delusions
  • Disorganised thought/speech
  • Movement disorders
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15
Q

What are the negative symptoms of schizophrenia?

A
  • social withdrawal
  • anhedonia
  • lack of motivation
  • poverty of speech
  • emotional flatness
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16
Q

Outline the cognitive symptoms of schizophrenia

A
  • impaired working memory
  • impaired attention
  • impaired comprehension
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17
Q

Which symptoms must persist for a patient to be classed as schizophrenic

A

2 or more of these symptoms must persist for >6months to be classed as schizophrenia

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18
Q

What are hallucinations?

A

Perception experienced without stimulus. (Functional Hallucination)
Most commonly auditory

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19
Q

What do SCZ patients commonly hear during auditory hallucinations

A

Patients hears
Voices talking about them (3rd person)
Voices talking to them
Voices giving a running commentary
Voices echoing their thoughts (thought echo)
Patients may engage in a dialogue with the voices or obey their commands.

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20
Q

What are delusions?

A

A fixed/ unshakable belief. Not consistent with cultural/ social norms
Often paranoid or persecutory

E.g. under control of an external influence, thoughts known to other people because they are transmitted by radio and TV
Passivity of thoughts and actions

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21
Q

What are motor, volitional and behavioural disorders?

A

Peculiar forms of motility, stupor, mutism, stereotypy, mannerism, negativism, spontaneous automatism, impulsivity

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22
Q

Give examples of motor, volitional and behaviour disorders

A

Stereotypies: purposeless, repetitive acts
Bizarre postures, strange mannerisms
Altered facial expression – grimacing

State of catatonia – motionless, mute, expressionless, uncomfortable or contorted postures
State of catalepsy – waxy flexible

Bouts of extreme hyperactivity (destructiveness; walk around naked)
Impulsive behaviour – violent acts; murder w/o reason

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23
Q

What is formal thought disorder

A

A disorder of conceptual thinking, reflected in speech that is difficult to understand and rapid shifts from one subject to another. New words are invented (neologisms).

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24
Q

Give examples of formal thought disorder

A

Disturbances in thinking → unintelligible speech

Derailment of speech

Loosening of associations; failure to follow train of thought to its conclusion

Poverty of speech (speech fails to convey sense/information)
- Manifests as distorted or illogical speech

25
Q

What is meant by social withdrawal?

A

Patients withdraw from their families and friends and spend a lot of time on their own.
Lack of initiative or motivation
Do not want to do anything.
No longer interested in things that used to interest

26
Q

What are cognitive deficits?

A

Deficits in SELECTIVE attention, problem solving and memory
Blunted affect
Decreased responsiveness to emotional issues.
Incongruous affect. Expression of affect inappropriate to circumstances.

27
Q

Describe SCZ patients ‘insight’

A

An understanding of what is wrong.
Insight lacking in schizophrenia.
Patients usually do not accept that anything is wrong or that treatment is necessary.

28
Q

What genetic factors lead to SCZ?

A

SCZ not directly inherited but can ‘run’ in families

there are candidate risk genes

  • gene deletions
  • gene mutations
29
Q

What environmental factors contribute to schizophrenia?

A
  • seasonal
  • maternal influenza
  • early-life stress
  • drug use (cannabis esp.)
30
Q

What role does nature and nurture have in developing SCZ?

A

A person may not develop SCZ if they have only the genetic risk factors or experience of the environmental factors. It is current thinking that a person needs to have both in order for the disease to manifest

31
Q

What results have twin studies shown regarding SCZ?

A

> study a monozygotic twin to see what the chances are of the other twin developing SCZ
50% chance of developing schizophrenia if one twin diagnosed
~14% chance of developing schizophrenia if one twin diagnosed - dizygotic

32
Q

What are the candidate genes seen in schizophrenic patients?

A

Some of the ‘risk’ or ‘candidate’ genes for schizophrenia

  • COMT (enzyme metabolising L-DOPA)
  • DISC1
  • GRM3 (glutamate metabolism)

Possessing these abnormal genes does not mean you will definitely get schizophrenia – similarly, some people who have schizophrenia do not have these genetic abnormalities

33
Q

How does maternal influenza lead to schizophrenic patients?

A 
Season of birth: influenza
Pregnant women in the UK are advised to be vaccinated against seasonal flu
- Low birth weight
- Premature birth
- Asphyxia during birth

These are all causes of early-life stress

34
Q

Outline the stresses previously seen to cause SCZ

A
  • Moving country
  • Early-Life Bereavement; Cohort under 18 (Denmark & Sweden)
  • Loss of >1 first-degree relative further increased risk
  • Loss of job/home/relationship
  • Physical/emotional/sexual abuse

> The mechanism by which stress may trigger schizophrenia is unknown

35
Q

How is drug use related to SCZ?

A

Cannabis use in early life (~15 years)

  • Amphetamine
  • Cocaine
  • LSD
36
Q

What are the different pathophysiologies of schizophrenia?

A 
Dopamine hypothesis
Brain structure differences
Hypofrontality
NMDA receptor hypofunction
Oxidative Stress
Neuroinflammation
37
Q

What is the importance of DA pathways?

A

Involved in:

  • Movement
  • Cognition
  • Emotions
  • Motivation
  • Reward
38
Q

How does DA lead to schizophrenia?

A

Schizophrenia – overactivity of DAergic, mesolimbic pathways

39
Q

What causes positive symptoms of SCZ?

A

Positive symptoms – hyperDAergic in mesolimbic system (↑ D2 )-but D2 antagonists do the same

40
Q

What causes the negative SCZ symptoms?

A

Negative symptoms – hypoDAergic activity in mesocortical system (↓ D1 )=>decrease cognition
D4 involved? But selective D4 antagonists not effective

41
Q

how can we combat the SCZ symptoms?

A

So we need to increase DAergic transmission in mesocortical regions, decrease DAergic transmission on mesolimbic regions

42
Q

What is the evidence against DA theory of schizphrenia?

A

No clear change in CSF HVA concentration

No change in DA receptors in drug-free patients (Increased D2 receptors in p-m samples attributed to drug treatment)

43
Q

What brain structure abnormalities are linked to SCZ?

A
  • Overall brain size is slightly smaller
  • Reductions in grey matter
  • Enlarged lateral ventricles - smaller hippocampus

*Not all people with schizophrenia have such profound structural brain differences

44
Q

How is hypofrontality linked to SCZ?

A

Reduced blood flow to the frontal cortex

Functional MRI find hypofunctioning in frontal cortex - affects decision making

45
Q

What role does glutamate play in schizophrenia?

A

↓ [glutamate] and glutamate NMDA receptor density in the prefrontal cortex associated with negative symptoms

46
Q

What is the evidence supporting the glutamate theory of SCZ?

A

Transgenic mice with ↓ NMDA receptor expression showed:

Stereotyped behaviour & ↓ social interaction, responsive to antipsychotics

47
Q

How do NMDA antagonists also cause psychosis symptoms?

A 
NMDA antagonists (ketamine / phencyclidine)
Block NMDA receptors producing psychotic symptoms – hallucinations & thought disorder
48
Q

How does serotonin affect SCZ?

A 
Serotonin hyperactivity (5-HT) evidence:
Lysergic acid diethylamide (LSD): partial 5HT agonist– hallucinations

Many antipsychotics antagonise 5-HT receptors
5-HT activates DA pathways
- 5-HT2A antagonism – may contribute to antipsychotic effect
- 5-HT2A antagonism – may reduce movement disorder side effects

49
Q

What is the main current theory of schizophrenia?

A

Main current theory

  • Over stimulation of mesolimbic D2 receptors
  • Hypoactivity of frontal cortical D1 receptors
  • Reduced prefrontal glutaminergic activity
  • 5HT involved
50
Q

What are the treatments used to stabilise SCZ patients?

A

Antipsychotics – many also antagonise 5-HT receptors (esp 5-HT2A).

51
Q

What are the 2 types of antipsychotics used to treat SCZ patients?

A

Typicals

Atypicals

52
Q

Describe the typical antipsychotics used

A

Typicals

  • Also known as ‘first generation’
  • First developed in the 1950s
  • Mainly antagonise D2 receptors
53
Q

What are atypical antipsychotics?

A

Atypicals

  • Also known as ‘second generation’
  • First developed in the 1980s
  • Mainly antagonise D2 and 5-HT2A receptors
54
Q

What are the different dopaminergic pathways involved in SCZ?

A

Nigrostriatal pathway
Reward pathway
Mesolimbic pathway
Tubero-hypophyseal pathway

55
Q

What is the nigrostriatal pathway?

A

dopaminergic neurons project onto substantia nigra to the striatum where DA is released ⇒ movement (seen in PD)

56
Q

Outline the reward pathway

A

Reward pathway: Dopaminergic neurons projecting from the ventral tegmental area to the nucleus accumbens

57
Q

What is the mesolimbic pathway?

A

Mesolimbic Pathway: neurons projecting from the amygdala to the hippocampus

Hyperactivity of this pathway is associated with positive SCZ symptoms
Blocking this D2 receptors produces antipsychotic effects

58
Q

What is the role of the tubero-hypophyseal pathway?

A

Tubero-hypophyseal pathway: DA released from hypothalamus as neurohormone to act on D2 receptors on the pituitary ⇒ decreased PL

Neurology (20 decks)

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