Schizophrenia Flashcards
What is the dopamine theory of schizophrenia?
Dopamine found to act as a neurotransmitter involves in symptoms of schizophrenia
The pathway produces the most distressing symptoms, functional impairment
Is schizophrenia a purely dopamine problem?
No!
Which pathway for schizophrenia do you want to target?
Mesolimbic dopaminergic pathway
Limbic system is for
Behavioural and emotional: feeding, fight or flight, protection
________ dopaminergic pathway is affected in Parkinson’s
Nigrostriatal
What is the ideal antipsychotic
Pure D2 antagonist, only in the mesolimbic pathway
Glutamatergic hypothesis of schizophrenia
Altered NMDA receptor subunit expression (ketamine can induce psychotic symptoms, as well as dissociation and indifference)
What % of dopaminergic receptors do you want to block?
60-80%
What are some dopaminergic side effects?
Extrapyramidal side effects Neuroleptic malignant syndrome
Hyperprolactinaemia
Akathesia/restless legs
Extra pyramidal side effects examples
Acute dystonic reaction (onset in minutes, increasing muscle tone, tongue protrusion)
Parkinsonism
Tardive dyskinesia (long term and often permanent, involuntary repetitive orofacial movements)
In schizophrenia, there is an excess of ________
Dopamine
Treat EPSE
Procyclidine
Akathisia
Inability to sit
Pacing/poor sleep/rocking from foot to foot
How do you treat akathisia ?
BB !
Benzodiazepines
1st generation anti-psych SE vs 2nd
1st: EPSE
2nd: weight gain, sedation
Best anti-psychotic, when do you use?
Clozapine
-ve syndrome, anti-suicidal
SIGNIFICANT SIDE EFFECTS!
Side effects of clozapine
Agranulocytosis !!! Lowered seizure threshold Myocarditis Constipation Weight gain Sedation Sialorrhea
1st line antipsychotic
2nd generation, then 1st or second
Examples of first generation
Chlorpromazine
Haloperidol
Examples of 2nd generation
Clozapine
Olanzapine
Risperidone
Paliperidone
Inheritance % of schizophrenia
78
During pregnancy, what would increase risk of schizophrenia?
2nd trimester viral illness
Pre-eclampsia, fetal hypoxia, C-section
Risk of schizophrenia increased by 50% by childhood ___ _____ _______
Viral CNS infection
Risk of psychosis is increased by substance misuse of
Amphetamines, cocaine, cannabis
Schizophrenia and the brain
Enlarged lateral ventricles
Reduced frontal lobe volume and grey matter
It is assumed that schizophrenia is due to ________ activity of dopaminergic activity in the brain
Increased
Mesolimbic/cortical system is for
Emotions/reward system
D1 receptor family action
Stimulates cAMP
D2 receptor family action
Inhibits adylyl cyclase
Inhibit Ca2+ channels
Open K+ channels
What is the most abundant dopamine receptor in brain?
D1
What kind of dopamine hyperactivity leads to psychosis?
Subcortical
What kind of dopamine hypo activity leads to negative and cognitive symptoms?
Mesocortical
Genes involved in brain pathology of schizophrenia
Neuregulin
Dysbindin
DISC-1
What is neurkgulin?
Signalling protein that mediates cell-cell interactions and plays critical roles in the growth and development of multiple organ systems
What is dysbindin essential for?
Adaptive neural plasticity
