Schizophrenia (neuro) Flashcards

1
Q

Psychotic disorders: background

A
  • Major psychoses (‘madness - cancer of mental illness’)
  • Examples:
    • Schizophrenia•
    • Schizoaffective disorder = schizophrenia and bipolar disorder
    • Delusional disorder
    • Some depressive and manic illnesses
  • Schizophrenia is the most important of the above for the following reasons:
    1. Early in onset
    2. Prevalent
    3. Disabling and chronic
  • 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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2
Q

Prevalence of schizophrenia

A
  • Affects up to 1% of the population
  • No significant influence of culture, ethnicity, background,
    socioeconomic groups
  • Increased in urban areas
  • Difference between sexes:
    • Men show an earlier age at onset, higher propensity to negative symptoms, lower social functioning, and co-morbid substance abuse than that is women, whereas women display relatively late onset of the disease with more affective symptoms.
  • Before the illness can be recognised there is often a phase in late teenage years associated with social isolation, interest in fringe cults, social withdrawal
  • A chronically disabling condition; responsible for a great deal of the population’s morbidity
  • In the UK, the cost of treating a patient with schizophrenia through their life is about six times the cost of treating a patient with heart disease.
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3
Q

Classes of schizophrenia

A
- Positive:
• hallucinations (eg visual, auditory)
• delusions
• disorganised thought/speech
• movement disorders
-  Negative:
• social withdrawal 
• anhedonia
• lack of motivation
• poverty of speech
• emotional flatness
-  Cognitive:
• impaired working memory
• impaired attention 
• impaired comprehension
- 2 or more of these symptoms must persist for at least 6 months to be classed as schizophrenia
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4
Q

Hallucinations

A
  • Perception experienced without stimulus (functional hallucination)
  • Most commonly auditory
  • 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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5
Q

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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6
Q

Motor, volitional and behavioural disorders

A
  • Peculiar forms of motility, stupor, mutism, stereotypy, mannerism, negativism, spontaneous automatism, impulsivity
    • 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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7
Q

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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8
Q

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 them.
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9
Q

Formal thought disorder

A
  • Disturbances in thinking -> unintelligible speech
  • Derailment of speech
  • Loosening of associations; failure to follow train of though to its conclusion
  • Poverty of speech (speech fails to convey sense/ information)
    • Manifests as distorted or illogical speech
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10
Q

Cognitive defects

A
  • Deficits in SELECTIVE attention, problem solving
    and memory
  • Blunted affect
  • Decreased responsiveness to emotional issues.
  • Incongruous affect
  • Expression of affect inappropriate to circumstances.
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11
Q

Insight

A
  • An understanding of what is wrong.
  • Insight lacking in schizophrenia.
  • Patients usually do not accept that any thing is wrong or that treatment is necessary
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12
Q

Four phases of schizophrenia

A
  1. The Prodrome:
    • Late teens/early twenties: often mistaken for depression or anxiety
    • Can be triggered by stress
  2. The Active/Acute Phase
    • Onset of positive symptoms
    • Differentiation of what is and isn’t real becomes difficult
  3. Remission
    • Treatment -> return to ‘normality’
  4. Relapse
    - Schizophreniform positive symptoms for at least a month, but under 6 months
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13
Q

twin studies

A
  • 50% chance of developing schizophrenia if one twin diagnosed
  • ~14% chance of developing schizophrenia if one twin diagnosed
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14
Q

‘Canditate’ genes

A
  • we know the exact genetic anomalies that lead to these disorders:
    • Sickle-cell disease
    • cystic fibrosis
    • colour blindness
  • Some of the ‘risk’ or ‘candidate’ genes for schizophrenia:
    • COMT
    • DISC1
    • GRM3
  • Possessing these abnormal genes does not mean you will definitely get schizophrenia – similarly, some people who have schizophrenia do not have these genetic abnormalities
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15
Q

The aetiology of schizophrenia

A
Nature vs Nurture (genetics vs environmental factors)
- genetics:
• SCZ isn’t directly inherited, but can ‘run in families’
• ‘Candidate’ risk genes:
• Gene deletions
• Gene mutations
- environmental factors:
• Pregnancy/birth complications
• Stress
• Drug use
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16
Q

Pregnancy/birth complications

A
  • Season of birth: influenza
  • A Finnish study reported a spike in schizophrenia for
    people who were foetuses during the 1957 influenza
    epidemic
  • Pregnant women in the UK are advised to be vaccinated against seasonal flu
  • All causes of early-life stress
    • Low birth weight
    • Premature birth
    • Asphyxia during birth
17
Q

Stress

A
  • Moving country
    • Swedish cohort 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
18
Q

Drug use

A
  • Cannabis
  • Use in early life (~15 years)
  • Amphetamine
  • Cocaine
  • LSD
19
Q

Pathophysiology of schizophrenia

A
  • Dopamine hypothesis
  • Brain structure differences
  • Hypofrontality
  • NMDA receptor hypofunction
  • Oxidative Stress
  • Neuroinflammation
20
Q

Main DA pathways

A

Involved in:

  • Movement
  • Cognition
  • Emotions
  • Motivation
  • Reward
21
Q

Neurochemistry

A
  • Theories (controversial, not sure how DA involved):
    • Schizophrenia caused by endogenous, DA derivative, psychotogen
    • Schizophrenia – overactivity of DAergic, mesolimbic pathways
    • Positive symptoms – hyperDAergic in mesolimbic system (increased D2 )-but D2 antagonists do the same
    • Negative symptoms – hypoDAergic activity in mesocortical system (decreased D1 )=>decrease cognition
    • D4 involved? But selective D4 antagonists not effective
22
Q

Dopamine

A
  • (pharmacological evidence):
    • DA release (amphetamine) produces ‘schizophrenia’ (Carlsson 2000)
    • Amph enhances DA release in schizophrenics more than controls which makes the disease worse
    • D2 agonists produce stereotyped behaviour (not D1)
    • Reserpine depletes DA – controls positive symptoms
    • Strong correlation D2 blocking activity & antipsychotic action
    • DA release only in mesolimbic, mesocortical NOT nigrostriatal
23
Q

Dopamine hypothesis

A

Evidence against:

  • No clear change in CSF HVA concentration
  • No change in DA receptors in drug-free patients (Increased D2 receptors in samples attributed to drug treatment)
24
Q

Brain structure abnormalities

A
  • Overall brain size slightly smaller
  • Reductions in grey matter
  • Enlarged lateral ventricles – smaller hippocampus
    • Not all people with schizophrenia have such profound structural brain differences
25
Q

Hypofrontality

A
  • reduced blood flow to the frontal cortex

- reduced activity in frontal cortex?

26
Q

Glutamate evidence

A
  • NMDA antagonists (ketamine / phencyclidine)
    • Psychotic symptoms – hallucinations & thought disorder
  • decreased [glutamate] and glutamate receptor density in prefrontal cortex
  • Transgenic mice with decreased NMDA receptor expression
    • Stereotyped behaviour & decreased social interaction, responsive to antipsychotics
27
Q

Serotonin (5-HT) evidence

A
  • Lysergic acid diethylamide (LSD): partial 5HT agonist– hallucinations
  • Many antipsychotics antagonise 5-HT receptors
  • Main current theory:
    • Over stimulation of mesolimbic D2 receptors
    • Hypoactivity of frontal cortical D1 receptors
    • Reduced prefrontal glutaminergic activity
    • 5HT involved
28
Q

Types of treatment

A
-  Pharmacological
• Current
• Future therapies?
- Cognitive Behavioural Therapy (CBT)
- Electroconvulsive therapy (ECT)
29
Q

Antipsychotics

A
Typicals:
- Also known as ‘first generation’
- First developed in the 1950s
- Mainly antagonise D2 receptors
Atypicals:
- Also known as ‘second generation’
- First developed in the 1980s
- Mainly antagonise D2 and 5-HT2A receptors
30
Q

Antipsychotic

A

• Antipsychotic -> receptor blockade (muscarinic blockade):
- Beneficial for treating extrapyrimidal side effects
- Dry mouth
- Blurred vision
- Constipation
- Urinary retention
• Antipsychotic (alpha-adrenoceptor blockade) -> postural, hypotension, nasal congestion, hypothermia
• Antipsychotic (other) -> H1 sedation, 5-HT weight gain, photosensitisation
• Antipsychotic -> D2 receptor blockade

31
Q

D2 receptor blockade

A

• D2 receptor blockade -> cortex limbic system (mesolimbic system) -> psychological effects (antipsychotic)
• D2 receptor blockade -> basal ganglia (striatum) (nigrostriatal) -> movement disorders:
- Parkinsonism
- dystonia
- dyskinesia
- tardive
• D2 receptor blockade -> pituitary gland (prolactin) -> endocrine effects:
- breast swelling
- lactation
- impotence

32
Q

Sedation

A
  • can occur via two 2 different mechanisms
  • D2 receptor antagonism
  • Central H1 receptor antagonism
33
Q

Prolactin effects

A
  • Antiasychitics increase prolactin secretion
  • Gynaecomastia, milk secretion
  • Menstrual irregularities, impotence, weight gain
34
Q

Hypotension

A
  • Another ‘off-target’ effect
  • alpha1-adrenoceptor antagonism
  • Leads to hypotension
    • alpha1 activation = vasoconstriction
    • alpha1 inhibition = vasodilation
35
Q

Anticholinergic effects

A
  • Antagonism of muscarinic acetylcholine receptors
    • Salivary secretions: Dry mouth
    • Pupillary muscles: Blurred vision
    • Smooth muscle contraction: Constipation and Urinary retention
    • Blockade of mAChRs at the neuromuscular junction: alleviates EPSE symptoms
  • However, anticholinergics are thought to detrimentally impact upon cognition