Exam 2: Schizophrenia Flashcards
What illnesses have increased risk for schizophrenia?
Alzheimer’s, MS, insulin diabetes, muscular dystrophy
Schizophrenia costs us ____
Effects ____ worldwide
billions worldwide
$63 billion
> 50 million
1 treatment for schizophrenia
Neuroleptics
mixed efficacy, multiple side effects, poor compliance
blurred vision, hypotension, arrhythmia, low bp, emotional disturbance, cognitive decline, tardive dyskinesia, abnormal lactation, weight gain, tremor, fatigue.
Medication: side effects no treatment
Positive symptoms of schizophrenia
delusions, hallucination’s, disorganized thinking,
movement (stereotypy, catatonia)
Negative symptoms of schizophrenia
Apathy Ahedonia Asocial behaviors Speech Reductions Loss of Attention
Cognitive- Executive function
poor memory, attention, inhibition, flexibility, planning, problem solving.
Delusions
idiosyncratic belief/impression, firmly maintained despite being contradicted by what is accepted as reality or rational argument
Delusions in delusional disorder
erotomaniac
grandiose
Schizophrenia
tormented followed sabotaged tricked spied-on ridiculed
Hallucinations
apparent perception of something not present (mostly auditory)
Disorganization
disordered thought, inappropriate emotions, hallucinations, and bizarre behavior.
Antipsychotics
Target DA receptors
Brains of Schizophrenic patients have too many DA receptors
Amphetamines’/meth/cocaine
Parkinson’s patients that OD on L-DOPA can exhibit psychosis
Problems with Antipsychotics
also target serotonin
patients don’t take regularly due to side effects
Schizophrenic brain
every region of brain has changes
no morphological marker for disease
no single region in every schizophrenic
enlarged ventricles
What have genetics studies shown in schizophrenia?
no bona fide susceptibility genes
Environmental risks for Schizophrenia
Cannabis, childhood trauma, vitamin D insufficiency, malnutrition, social defeat, infection induced activation of HERVs, smoking, social cognition. But not 100% associated with disease.
What is a functional approach to studying the brain?
Dendritic spines, if you look at individual circuits, tells you circuit is misfunctioning, know where to look for genes.
How do you study schizophrenic symptoms in animal model?
Endophenotypes- quantitate, heritable traits that can be studied in isolation in order to understand the disease in pieces rather than as a whole
22q11DS
DiGeorge/Velocardiofacial Syndrome
Abnormal craniofacial development
Heart/immune defects
90% learning disabled
~30% schizophrenia
What is the mouse used to model 22q11DS?
DF(16)1/+
deletion syndrome
genes are about the same
mouse study: consequences in hippocampus
age-dependent spatial memory deficit
early adulthood have memory deficits
SERCA2 protein is elevated in Df(16)1/+ hippocampus at 16 weeks
Beta-actin elevated on onset
Ca2+ in ER released when plasticity induced. Too much plasticity
SERCA2 protein in Df(16)1/+ hippocampus
elevated at 16 weeks
____ has elevated onset in mouse
beta-actin
Ca2+ in ER released when ____ induced. How does this effect moues model?
plasticity induced
Too much plasticity when calcium in ER released
Df(16)1/+ mice display
age-dependent increase in long-term potentiation
What blocks synaptic disparities of Df(16)1/+ mice
SERCA inhibitors
DGCR8 gene in microRNA biogenesis
Microarray
of microRNA only 3 predicted on circa
model for Dgcr8+- effect on hippocampal function- some target certain protein. Why? 22q11DS. If you lose controllers, circuit goes up, age of onset phenotypes in mouse. More NT released.
miRNA rescue
Adenoviral strategy
rescue plasticity deficit in Dgcr8+/-mice
Describe the model for Dgcr8+/- effect on hippocampal function
less miRNA-25
can’t inhibit SERCA, lots of Ca2+ in ER
lots Ca2+ release from vesicles
What happens to SERCA2 levels in patients with schizophrenia?
increased in prefrontal cortex and hippocampus
