Mental Health Pharmacology Schizophrenia Flashcards
Which neurochemicals are imbalanced in the brain in SZ?
DA
* Glu (glutamate)
Ach, 5HT, GABA
What are the positive symptoms of SZ?
Hallucinations (auditory, visual), delusions, thought insertion, disorganised thought processes, disorganised speech, disorganised behaviour, agitation, catatonia (non response to stim)
What are negative symptoms of SZ?
Flattening of emotional responses, low mood, loss of motivation, lack of energy, social withdrawl, anhedonia (loss of pleasurable activities), speech and language deficits, poor self care
What are cognitive symptoms of SZ?
Impaired working memory, loss of attention, impaired decision making
Describe the epidemiology of SZ:
Prevalence 0.3-0.7%
Incidence 0.3 in 1000 so lifetime risk is 1%
Typical onset of +ve symptoms is late adolescence/ early adulthood (15-25)
Same incidence rates in male to female, but typically there is later onset in females
What is the mortality like in SZ?
50% increased mortality
Life expectancy decreased by 20-30 years
Increases CV risk, lifestyle, suicide
Describe the aetiology of SZ:
Genetic (70-80%) and environmental (20-30%)
What are the risk factors for SZ?
Family history
Developmental
Environment
Describe how family history can be a risk factor for SZ:
50% concordance in identical twins
20% in non identical
10% siblings
15% parent
Describe how developmental factors can be a risk factor for SZ:
Pre-natal (before birth) factors e.g maternal stress- viral infection, birth trauma
Neurodevelopmental abnormalities
Describe how the environment can be a risk factor for SZ:
Stressful life events
Urban environment
How can genetics be a link to SZ?
Many SZ susceptibility genes have been identified
Involved in neuronal development, synaptic organisation and function- neurotransmission:
-receptors
-TFs
-protein turnover
-ion channels
-structural proteins
-epigenetics
Describe the pathophysiology of SZ:
Increase in size of ventricles
Loss of grey matter (thinning of cortex)
Decreased white matter volume
Altered activity in dorsolateral pre-frontal cortex, ventromedial pre-frontal cortex, amygdala and hippocampus
Change in neurotransmitters
Describe the loss of grey matter in the pathophysiology of SZ:
Nº neurons unchanged (not neurodegenerative disease)
Synaptic connections- size of dendritic tree so less connections:
-increase dendritic pruning, means less connections
-many susceptibility genes involved in synaptic maintenance
Describe a decreased white matter volume in the pathophysiology of SZ:
Decrease in number of oligodendrocytes (cells which make myelin sheath)
What is the function of the dorsolateral pre-frontal cortex?
Decision making, motivational drive
What is the function of the ventromedial prefrontal cortex?
Emotional function
Describe pharmacological evidence for the dopamine hypothesis:
Drugs that cause DA release/ increase in synaptic conc (e.g amphetamine, cocaine) can cause psychosis
Drugs that deplete DA (e.g reserpine) decreases psychosis
D2 agonists (e.g bromocriptine) exacerbate sz
A SE of dopaminergic drugs is hallucinations
What receptors do all antipsychotics block and what does this mean?
All block D2 receptors
Decrease psychotic (+ve) symptoms
Correlation between clinical potency and affinity of antipsychotic drugs for the D2 receptors
What is psychosis in sz due to?
Over activity of dopaminergic neurons in the mesolimbic pathway causing the +ve symptoms of sz