Schizophrenia Flashcards
What neurochemicals are imbalanced in the brain for schizophrenia?
D
Glutamate
ACh, 5-HT, GABA
symptoms of schizophrenia
positive symptoms - hallucinations (auditory, visual etc), delusions (paranoia), thought insertion (putting thoughts into their heads), thoughts broadcasting (thinks others can hear their thoughts), disorganised speech/ behaviour, agitation, catatonia
Negative- flattening of emotional responses, low mood, loss of motivation, social withdrawal, speech and language deficits, poor self care, no interest in activities.
cognitive- impaired working memory, loss of attention, impaired decision making
What physical changes occur in the brain from schizophrenia?
Larger ventricle size
loss of grey matter but no. of neurones unchanged- size of dendritic tree smaller.
Decrease in white matter (and oligodendrocytes)
Altered activity in top of pre-frontal cortex, amygdala, hippocampus.
Neurotransmitters
The dopamine hypothesis
Drugs that increase dopamine cause psychosis, drugs that decrease dopamine inhibits psychosis, D2 agonists (bromocriptine) exacerbate schiz.
Antipsychotics all block D2 receptors (dec. positive symptoms)
In the dopamine hypothesis, where is overactivity of dopaminergic neurones located?
What type of symptoms does this cause?
Mesolimbic pathway
Positive symptoms
What pathway is there decreased activity of DA?
What symptoms do these cause?
Mesocortical pathway
Negative symptoms
What is the mesolimbic and Mesocortical pathway?
Reward pathway mesolimbic
Mesocortical cognition and thought
The glutamate hypothesis
newer theory
lower activity at glutaminergic synapses in pyramidal neurones in pre-frontal cortex
reduced signalling via NMDA receptors
explains all symptoms of schizophrenia
Explains all DA changes in mesolimbic and cortical pathway
*decr. signalling via NMDA receptors causes increased activity in mesolimbic but decreased activity in mesocortical pathway
What genes are susceptibility genes
GRIN2A (NMDAR subunit)
GRIA3 (AMPAR subunit)
Dysbindin (synaptic structure and forming post synaptic density)
Neuregulin ^^
COMT and MAO
First gen. antipsychotics (typical)
chlorpromazine,halperidol
Second gen. antipsychotics (atypical)
Clozapine, risperidone, olanzepine, quetiapine
How do antipsychotics work generally
block D2 receptors in mesolimbic pathway
Also blocks D2 receptors in other dopaminergic pathways
What symptoms occurs due to blocking D2 receptors on other pathways with schizophrenia treatments
Nigrostriatal pathway- motor effects (EPSEs)
(involuntary movements, psuedo-parkinsonism, spasm in face and neck, tardive (late) dyskinesia’s (involuntary / repetitive movements)
Tuberoinfundibular pathway- dopamine usually blocks prolactin sec. so therefore increased prolactin secretion when D2 blocked. Causes breast development/ lactation/ pain, amenorrhea/ low fertility in women, loss of libido
mesocortical - blocking a deficient pathway, therefore can worsen negative symptoms
Inhibition of reward pathways by mesolimbic pathways enhances negative s/e
What do second gen antipsychotics have to reduce side effects
*antagonist activity at 5HT2A receptors to decrease prolactin sec. and increase DA in striatum, increase glutamate in cortical pyramidal cells. (olanzepine and clozapine)
*Improve selectivity for D2 over D1 receptors (risperidone)
*improving selectivity for D2 receptors over all other receptors (sulpiride)
*Rapid dissociation from D2 receptors (quetiapine)
*Partial agonist at D2 receptors (aripiprazole)
*Action at muscarinic receptors (if antimuscarinic properties, helps side effects)
What side effects show from antipsychotics that inhibit muscarinic receptors
anticholinergic- dry mouth, skin, bradycardia, constipation
What side effects show from antipsychotics that inhibit alpa1
postural hypotension (constriction of vascular smooth muscle)
hypotension
What side effects show from antipsychotics that inhibit H1 (histamine)
if in brain, sedation!!
What other side effects can occur from antipsychotics
weight gain
insulin resistance and hyperlipidaemia (metabolic syndrome)
incr. CVD
type 2 diabetes from metabolic syndrome
neuroleptic malignant syndrome
Prolong QT interval- can cause arrhythmia
Neutropenia and agranulocytosis (clozapine esp. monitor WBC)
