Schizophrenia Flashcards
What is schizophrenia?
- A type of major psychoses (madness).
- It has an early onset, prevalent and is a disabling and manic illness.
- It is considered a mental state that is out of touch with reality.
- Abnormalities of perception, thought and ideas
- Profound alteration in behaviour
Prevalence of Schizophrenia
- Affects up to 1% of population which is relatively high
- No significance influence of culture, ethnicity, background or socioeconomic group
- However, present in urban areas.
- No differences between sexes unlike depression
- Before the illness can be recognised, therefore is often a phase in late teenage years associated with isolation, and social withdrawal.
Phases of schizophrenia
- The prodrome
- The active/acute phase
- Remission
- Relapse
What is the prodrome phase of schizophrenia?
- Late teens/early twenties often mistaken for depression or anxiety
- Can be triggered by stress
- Negative symptoms
What is the active/acute phase in schizophrenia?
- Onset of positive symptoms
- Differentiation of what is and isn’t real is not present
- Hallucinations and delusions
What is the remission phase in schizophrenia?
- Treatment and returning back to normal
- Schizophreniform is positive symptoms for at least a month but under 6 months before relapse
What are the three catergories of Schizophrenic symptoms?
Positive
Negative
Cognitive
2 or more symptoms must be persist for at least 6 months
What are the positive schizophrenic symptoms?
- Increase in abnormal behaviour
- Visual and auditory (See and hear things)
- Somatosensation - feel things that aren’t there
- Delusions - disorted speech
What are the negative schizophrenic symptoms?
- Decrease in normal behaviour
- Social withdrawal
- Lack of enjoyment and emotion
- Poverty of speech
- Emotional flatness
- Anhedonia - no pleasure in anything
What are the cognitive schizophrenic symptoms?
- Cognitive defect (can’t process thoughts)
- Impaired memory, attention and comprehension
Hallucinations
- Perception experiences without stimulus
- Auditory/hearing voices
- Patients may engage with the dialogue with the voices or obey their commands
Delusions
- A fixed unshakable belief
- Often paranoid or persecutory
Potential causes of schizophrenia
- Nature
- Nurture
Nature causes of schizophrenia
Genetics
- Tends to run in families, not directly inherited but can be linked in the family tree e.g. great uncle has it or another distant family member
- Twin studies have shown 50% chance of getting schizophrenia if you have an identical twin that has it
- If it was only caused by genetic factors, there would be a 100% chance between identical twins
- This means that SCZ genes only predisposes you to the disease so other factors must be present
- COMT, DISC1 and GRM3 are some of the genes that predispose someone to the disease
What are the genes that predispose someone to schizophrenia?
COMT, DISC1 and GRM3
Nurture causes of schizophrenia
- Pregnancy or birth complications, including low birth weight, premature birth and Asphyxia during birth
- Season of birth -> influenza
- If the mother was in the 1st and/or 2nd trimester in the winter and got the flu, the risk of the baby developing schizophrenia when they are older is higher
- This is why pregnant women are advised to be vaccinated against seasonal flu
- General stress: moving, early love bereavement, loss of job, relationships etc
- Cannabis use in early life as well as amphetamine, cocaine and LSD.
Pathophysiology of Schizophrenia
- Dopamine hypothesis
- Brain structure differences
- Hypofrontality
- NMDA receptor hypofunction
- Oxidative stress
- Neuroinflammation
What are the three stages in the dopamine hypothesis?
- Hyperactivity of the mesolimbic pathway
- Hypoactivity of the mesocorticol
- Decreased tuberohypophyseal
How does hyperactivity of the mesolimbic pathway affect dopamine?
- Hyperactivity of the mesolimbic pathway which is linked to the reward symptom.
- Schizophrenia associated with abnormally high dopaminergic transmission
- Assumed because substances which cause overstimulation of dopamine receptors have similar symptoms to schizophrenia
- Amphetamine and Cocaine have SCZ symptoms and they block the uptake of dopamine
- The blocking of the D2 receptors in the mesolimbic pathway is associated with the antipsychotic effects and decrease in positive symptoms
How does hypoactivity of the mesocortical pathway affect dopamine?
- Associated with negative symptoms due to loss of cognitive control, motivation and emotion
- Therefore, dopamine levels in the mesolimbic need to be decreased and need to be increased in the mesocortical system
How does decreased tuberohypophyseal pathway affect schizophrenia?
- Therefore, no prolactin release inhibition and therefore men and women get enlargement of breasts.
Brain structure abnormalities in Schizophrenic patients
Overall, the brain of a SCZ patient is smaller. There is reduction in grey matter. There is also enlarged lateral ventricles and a smaller hippocampus
What is hypo-frontality?
Reduced blood flow to the frontal cortex showing hypoactivity of the frontal cortex and therefore there is distorted cognitive function in the SCZ patients
Glutamate hypothesis and schizophrenia
- Low number of NMDA receptors in the prefrontal cortex of SCZ patients
- NMDA antagonists are ketamine and phencyclidine which causes hallucinations and thought disorders
- NMDA low levels enhance mesolimbic DAegic activity
- Theory is that low levels of glutamate and DA exert excitatory and inhibitory effects on GABAergic striatal neurons projecting to the thalamus and sensory cortex.
- Too much or too little action will disable the gate and allow unwanted sensory information to the cortex.
- Low glutamate is thought to be linked to negative symptoms
Serotonin hypothesis
- Increased serotonin levels are linked with SCZ episodes
- Agonists of serotonin lead hallucinations serotonin activates the DA pathways
What is the overall hypothesis of dopamine?
- Over stimulation of mesolimbic D2 receptors
- Under stimulation of mesocortical D1 receptors
- Under stimulation of glutamate NMDA receptors
- Over stimulation of serotonin receptors
Typical antipsychotics
- Antagonise D2 receptors
- Takes longer to work
- Mainly used for positive symptoms
- As with most schizophrenic drugs, severe side effects
Types of typical antipsychotics
- Chlorpromazine
- Fluphenazine
- Haloperidol
- Flupentixol
Atypical antipsychotics
- Antagonise D2 and 5-HT2a receptors
- Better for negative symptoms
- Fewer side effects as less potent D2 antagonists
- Activation of 5HT2a causes hallucinations so help reduce hallucination which is a use for positive symptom
Examples of Atypical antipsychiotics
- Clozapine
- Olanzapine
- Risperidone
- Aripiprazole
Overall effect of Antipsychiotics
- Binding to D2 receptors causes blockage in the mesolimbic pathway leading to antipsychotic effects and reduces reward/pleasure
- Binding to D2 receptors in the nigrostriatal pathway leading to movement disorders due to movement control such as Parkinsonism
- Binding to D2 receptors in the tubero-hypophyseal pathway leads to increased prolactin production due to no inhibition and therefore breast enlargement
- Binding to muscarinic receptors leads to blurred mouth, blurred vision and constipation, as well as urinary retention
- Binding to the adrenoceptors leads to hypotension and other CVS problems
- Binding to other receptors can lead to weight gain, sedation
