Schizophrenia (EL) (DONE) Flashcards
Overview
Affects about 1% of the population
Typically appears in early adulthood (18-30 years)
Chronic, debilitating and 5-10% of sufferers may commit suicide, chronic cases account for majority of long stay psychiatric patients
Progressive disintegration of personality and the relationship between self and world
Definition
Kraepelin popularised the term dementia praecox to describe a condition where there is a breakdown of the personality at a relatively young age
Diagnostic criteria
Four domains: positive, negative, mood, cognition
2 out of 5 characteristic symptoms must be present: delusions, hallucinations, disorganised speech, abnormal psychomotor behaviour, negative symptoms
For one month in the last 6, with social/occupational dysfunction
Features of schizophrenia
Positive: delusions, hallucinations, disorganization
Negative: decreased emotional range, decreased expression of emotion, decreased motivation, decreased interests, decreased social drive, poverty of speech
Mood: depression
Cognitive: deficits in working memory, attention, executive function, problems with interpersonal relationships
Positive symptoms
Abnormal by their presence, at least one of these must be present
Auditory hallucinations (voices repeating the individual’s thoughts)
Thought disorders- paranoid delusions e.g. they are reading and controlling my thoughts
Physical catatonia (maintaining strange posture for long periods)
Disorganised speech
Negative symptoms
Abnormal by their absence, they can be true or reactive i.e. secondary to the positive symptoms
Catatonia
Emotional problems- social withdrawal, blunting of emotions, reduced speech
Mood and cognition
Cognition- deficits in working memory, attention, executive function, problems with interpersonal relationships
Mood- affective symptoms- often depressed
Drug and alcohol abuse are common and can cause problems with diagnosis and treatment
Aetiology
Both genetic and environmental factors contribute
CT (CTA or MRI) shows that there is loss of cortical neurones, reduced brain size, increased ventricular size (soft neurological signs). PET scans also show changes in the mesolimbic system.
It is considered neurodevelopmental rather than neurodegenerative
Genetic link
In monozygotic twins with identical genes, if one twin develops schizophrenia, there is a 50% chance the other will also
Siblings of a schizophrenic show an increased risk of developing the disorder
Areas of the brain involved
There are possible deviant connections between nerve cells- nerve sprouts called spines which form in childhood are 50% shorter and wider than usual
As a consequence information processing is impaired i.e. faulty circuitry is in place
Thalamus is pivotal in information processing
Imaging studies suggest that the volume of the thalamus is reduced in schizophrenia
Thalamic nuclei may be affected
Dopaminergic theory
Amphetamine causes release of DA, producing a syndrome indistinguishable from schizophrenia in recreational users
D2 receptor agonists worsen the symptoms
Modest increase in D2 receptor density in the striatum
Serotonergic theory
Lysergic acid diethylamide produces symptoms akin to schizophrenia
Many antipsychotics act at 5HT receptors as antagonists
5HT pathways and dopaminergic pathways are linked
Serotonin involvement in schizophrenia
Post mortem studies: increase in 5HT transmission and 5HT transporter density in subcortical regions, decrease or no change in 5HT receptor density in prefrontal cortex
Glutamatergic theory
Blockade of NMDA receptor channels by phencyclidine or ketamine produce schizophrenia-like symptoms
Glutamatergic neurones feed an excitatory input into striatal GABAergic neurones (inhibited by dopamine), so gating sensory input at the thalamic level
NMDA antagonist stimulated hyperlocomotion
MK-801 and PCP induce a behavioural syndrome that includes hyperlocomotion, head weaving, body rolling, ataxia and reduced rearing in rats
Conventional and atypical APDs reduce MK-801 stimulated hyperlocomotion
First generation antipsychotics
All reduce dopaminergic transmission (D2 antagonism)
Older first described drugs, D2 receptor antagonists, e.g. butyrphenones- haloperidol, phenothiazines- chlorpromazine/thiordizine
Reduce the positive symptoms of schizophrenia
Block DA inhibition of prolactin release (resultant increases in plasma levels leads to reduced gonadal function and lactation)
Higher risk of effects on nigrostriatal pathway causing extrapyramidal side effects
Second generation antipsychotics
Thioridazine, sulpiride, risperidone and clozapine
5HT and dopamine receptor antagonism
Some e.g. risperidone reduce negative symptoms
Lower risk of extrapyramidal effects but associated with increase of metabolic side effects (weight gain, diabetes, headache)
Third generation antipsychotics
Aripiprazole is only drug in this class currently licensed
Partial D2/D3 agonist
Partial 5HT1a agonist
Four dopamine pathways
Mesolimbic (SCZ- increase in DA causes positive symptoms)
Mesocortical (SCZ- DA hypoactivity: negative, cognitive and affective symptoms)
Nigrostriatal (drugs- EPS and TD side effects)
Tuberohypophyseal (drugs- hyperprolactinaemia side effects)
Effects of antipsychotics on prolactin secretion
Hypothalamic dopamine has an inhibitory influence on the output of the anterior pituitary (hypothalamic-pituitary axis)
NB depot injection is a good strategy when there are issues of compliance
Drug side effects
Dyskinesias- DA function increases Parkinsonism-like (akinesia)- DA function decerases Tardive dyskinesias (facial muscles, takes months or years to occur)- DA function increases
Antipsychotic side effects
Typical agents- stiffness, shakiness, slowed thinking, restlessness, BP changes, sex life problems
Atypical agents- sleepiness and slowness, weight gain, diabetes risk, BP changes, sex life problems, with higher doses or long term use stiffness and tardive dyskinesia
Clozapine- affects bone marrow and production of white blood cells making susceptibility to infection more likely (weight gain, constipation, over production of saliva, epilepsy risk)
Neuroleptic malignant syndrome
Life threatening idiosyncratic reaction to antipsychotic drugs
Characterized by fever, altered mental status, muscle rigidity and autonomic dysfunction
Associated with virtually all neuroleptics, including newer atypical antipsychotics
Rare but requires prompt recognition to prevent significant morbidity and death
Treatment includes immediately stopping the offending agent and implementing supportive measures, as well as pharmacological interventions in more severe cases
