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)
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.
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
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.
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
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
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).
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.
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
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.
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
12
Q
Four phases of schizophrenia
A
- The Prodrome:
• Late teens/early twenties: often mistaken for depression or anxiety
• Can be triggered by stress - The Active/Acute Phase
• Onset of positive symptoms
• Differentiation of what is and isn’t real becomes difficult - Remission
• Treatment -> return to ‘normality’ - Relapse
- Schizophreniform positive symptoms for at least a month, but under 6 months
13
Q
twin studies
A
- 50% chance of developing schizophrenia if one twin diagnosed
- ~14% chance of developing schizophrenia if one twin diagnosed
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
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
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
