Schizophrenia Flashcards
Prevalence
about 1% of the population
Age of onset
18-32 years
Concordance rate
if your monozygotic twin has schizophrenia, 48% risk of developing schizophrenia; probability increases for those who are more related, genes predispose, environment plays a role
Positive Symptoms
hallucinations (auditory), disordered thought processes, bizarre behavior
Negative symptoms
social withdrawal, flat affect, anhedonia, catatonia, reduced motivation
Cognitive symptoms
working memory, executive function, attention
Brain differences
cerebral atrophy, ventricle enlargement, hippocampal cells disorganized, abnormal myelination, hypofrontality
Brain differences; ventricle enlargement
not as strong an effect in females compared to males
Brain differences; abnormal myelination
abnormal myelination and organization of white matter tracts reduces connectivity between different brain regions
Two hit model
1) perinatal effects in a genetically vulnerable individual cause altered brain development 2) neurodevelopmental errors in adolescence + environmental factors produces diagnosable symptoms
Neonatal ventral hippocampal lesion model
lesion in rat brains that creates similar behavioral symptoms as schizophrenia
Prenatal inflammation model
polyl:C and lipopolysaccharide used for maternal immune activation, increases levels of pro-inflammatory cytokines that produce structural, cognitive, and behavioral outcomes that resemble schizophrenia
DA hypothesis
positive symptoms are caused by excessive mesolimbic DA activity
DA hypothesis support
amphetamines produce positive symptoms that can be reversed by DA antagonists; strong correlation between D2 receptor blockade and reduction of symptoms
DA hypothesis problems
DA antagonists do not work for everyone; negative symptoms are unaffected by drug therapy, many with schizophrenia have normal brain DA levels; many atypical neuroleptic drugs do not have high D2 binding affinity
DA imbalance hypothesis
symptoms are due to reduced DA function in mesocortical regions and excess DA function in mesolimbic regions
The hypoglutamate hypothesis
schizophrenia results from decreased activation of glutamate NMDA receptors, cortical glutamate normally inhibits striatal DA
Treatment law of thirds
⅓ respond well to drug therapy and have relatively normal social lives, ⅓ have significant improvement in symptoms but need assistance with daily activities, ⅓ fail to respond to medication and are institutionalized
“Classic” “typical” 1st gen neuroleptics/antipsychotics
D2 antagonists
Thorazine
classic neuroleptic, a phenothiazine with a three ring structure that mimics DA
Haldol
a butyrophenone, classic neuroleptic
Classic neuroleptic presynaptic effects
reduce signaling
Classic neuroleptic postsynaptic effects
increase DA turnover
Classic neuroleptic side effects
sedation, hypotension, anticholinergic effects; extrapyramidal side effects = motor effects like tardive dyskinesia
Atypical second gen drug benefits
less motor-system side effects, alleviate negative and cognitive symptoms better
3 classes of atypical second gen drugs
selective D2 antagonists, dopamine system stabilizers, broad-spectrum anti-psychotics
Sulpiride
atypical second gen drug, selective D2 antagonist
Amisulpiride
atypical second gen drug, selective D2 antagonist
Abilify
atypical second gen drug, dopamine system stabilizer
Clozapine
atypical second gen drug, broad-spectrum anti-psychotic
Risperidone
atypical second gen drug, broad-spectrum anti-psychotic
atypical second gen drug additional binding
many bind to 5-HT 2A and 2C better
atypical second gen drug side effects
more weight gain
nAChR agonists
based on fact that 70-90% of people with schizophrenia smoke
