Schizophrenia Flashcards
Too little dopamine in nigrostriatial pathway causes what?
Extra side effects
What is the 3 hit model of SZ?
Genetic predisposition + peri-natal insult (around birth) + stress/life experiences = SZ
Prenatal environmental factors leading to inc risk of SZ
Perinatal complications (any birth complication), malnourishment, infection, vitamin D deficiency
Ventricles of schizophrenia patients
Enlarged
What does the glutamate hypothesis say?
Disturbance in glutamate systems causes negative and cognitive symptoms
What type of frontal lobe activity is seen in schizophrenia patients? What is this called?
Less frontal lobe activity. Hypofrontality
Most common type of schizophrenia
Impairment increasing with each of several episodes followed by negative symptoms (33%)
What produces further gray matter loss after the first psychotic episode?
Cannabis use
Olazapine, clozapine, and rispiridone
Atypicals
Where do atypicals work?
D2 and 5HT2A receptors
Subtle behavioral abnormalities; early effects of dopamine dysfunction and extraneous effects of genetic or environmental insults
Childhood
What are typical antipsychotics and what do they treat?
Dopamine antagonists that treat positive symptoms
Caused tardive dyskinesia
Typical antipsychotics
SZ patients have inc density of this receptor not related to history of cannabis use
cannabinoid receptors
Parts of the glutamate hypothesis
Reduced number of glutamate receptors, greater drop in glutamate with aging, and PCP blocks NMDA glutamate receptor and is a dopamine agonist
What do dopamine agonists do in schizophrenia?
Produce psychotic behavior (cocaine, amphetamines, L-dopa)
When is the typical onset for schizophrenia?
18-25
How do genes inc the risk of SZ?
The more similar the genes = the greater the risk
What does ketamine do?
Blocks NMDA receptor to not allow Ca to enter the cell so it cant depolarize.
Abnormalities at D2 receptors and greater dopamine synthesis and release leads to positive symptoms
Dopamine hypothesis
Positive symptoms of schizophrenia
Disorganized speech, hallucinations, delusions, disorganized behavior
Persistent negative symptoms; consequences of altered dopamine development on glutamate and GABA
Treatment
What does the dopamine hypothesis state?
Too much dopamine is linked to the positive symptoms of schizophrenia
Eyetracking and SZ relationship
Patients and 45% of their relatives show abnormal intrusions of saccades (jerky eye movements) in smooth pursuit tasks
Associated with relapses of psychotic symptoms
Cannabis
Early migration abnormalities in schizophrenia patients
Less clear ventricular zone is visible. Hard to see normal inside out growth
What are extrapyramidal symptoms?
Pseudoparkinsonism, acute dystonia, akathisia, TD. Movement problems created by typicals
What part of schizophrenia are we worst at treating?
Cognitive impairments
Cellular organization of schizophrenia patients
Disorganized. No nice lines of cell bodies and dendrites and axons are all over the place
What do most schizophrenic people exhibit in regard to what hand is dominant?
Non-right handed or ambiguous handedness due to higher degree of brain symmetry
What are the problems with the dopamine hypothesis?
How long it takes for behavioral changes, not responding to dopa antagonists, extra side effects, other receptors and transmitters involved
Too much dopamine in mesolimbic pathway causes what?
Positive symptoms
Too little dopamine in mesocortical pathway causes what?
Negative, cognitive, and affective symptoms
Too little dopamine in tuberohypophyseal pathway causes what?
Spontaneous lactation (hyperprolactinemia)
Other NTs involved in schizophrenia
5HT and acetylcholine
Altered dopamine development; genetic or environmental risk factors
Early development
How does cannabis use relate to genes and SZ?
Certain combinations of genes and cannabis use = greater risk of SZ
What specific area of the frontal lobe is less active in schizophrenia patients?
Dorsal prefrontal cortex
How do D2 antagonists create new symptoms and cure other symptoms?
Create = nigrostriatial pathway Cure = Mesolimbic
What happens in adolescence of schizophrenia patients?
Accelerated pruning
Negative symptoms of schizophrenia
Lack of motivation (avolition), flattened affect, alogia (speech problems)
How is schizophrenia treated with the modern hypothesis?
D2 antagonist for positive symptoms and D1 agonist for negative symptoms
Structural abnormalities in schizophrenia
Enlarged ventricles, smaller hippocampal volume, hypofrontality, higher degree of brain symmetry, adolescent loss of gray matter
Causes patients to be more susceptible to effects of SZ
Patients have higher levels of endogenous cannabinoids
What happens with 25% of patients and dopamine antagonists
They don’t respond to dopamine antagonists
Treat positive and negative symptoms without TD
Atypical
Less metabolic activity in frontal lobe
Hypofrontality
5HT role in schizophrenia
Regulates mood and emotions, interacts with dopamine, treated with atypicals
What do D2 antagonists do?
Prevent dopamine form binding to reduce positive symptoms
Where do typical antipsychotics work?
D2 receptors. Dopamine antagonists
What is wrong with limiting dopamine to treat schizophrenia?
Limiting dopamine could cause things like Parkinsons. Fine line between too little and too much dopamine
How are positive symptoms caused and treated in the modern dopa hypothesis?
Too much D2 activity in mesolimbic system treated with D2 antagonists
ACh role in schizophrenia
Important role in attention. 85% of SZ patients smoke (nicotinic ACh receptors)
Environmental risk factors for SZ
Urban areas, low SES, maternal exposure to viruses at critical prenatal periods, seasonality effect, geographical patterns
How are negative symptoms caused in the glutamate hypothesis?
Hyopactivity of NMDA glutamate receptor in VTA = lose excitatory drive in mesocorticol dopamine neurons = negative, cognitive, and affective symptoms
At least two of what must be present most of the time during a 1 month period for schizophrenia diagnosis?
Delusions, hallucinations, disorganized speech, grossly disorganized behavior, diminished emotional expression or avolition
What is the Wisconsin card sort task? What does it show?
Patients match cards based on feedback they receive. There is a rule for the way to do it and it will change over time. Shows cognitive flexibility/perseveration
How long does it take drugs to block receptors and how long does it take for behavioral effects to be seen from this?
Drugs = hours Behaviors = weeks
How are positive symptoms caused in the glutamate hypothesis?
Hypoactivity of NMDA glutamate receptor in VTA = cant inhibit mesolimbic dopamine neurons = positive symptoms
Associated with negative symptoms, might represent more widespread problem with default mode network associated with positive symptoms
Hypofrontality
Holding on to first rule they learned. Seen in schizophrenia patients
Perseverative error
Schizophrenia patients and the Wisconsin card sort task/cognitive flexibility/perseveration
They can get the first rule, but cant adapt to the new rule. They show perseverative errors
What do atypical antipsychotics do?
Dopamine and 5HT antagonists
How are negative symptoms caused and treated in the modern dopa hypothesis?
Too little D1 activity in the PFC (mesocoritcol pathway), treated with D1 agonists
What is used to treat SZ?
Atypicals and psychosocial rehabilitation
Clear dopaminergic abnormalities before manifestation of symptoms. Adolescence
Prodrome
Acute psychosis; dopaminergic flux
Disease onset
