11/30 Flashcards
Schizophrenia and creativity
Unusally high levels of creativity in both individual and family
% off US reports symptoms of Schizophrenia
1/3
Male vs Female Schizophrenia
no difference in prevalence
Difference in spike in onset (2d peak for women at 40s)
Paralytic dementia
sudden onset of delusions, caused by syphilis (1900 25% of patients suffered from)
Also, grandiosity, euphoria, poor judgment, impulsive behavior, disorderred thought and abnormal pupal contractions
Many psychological disorders have biological causes
Delusions
false beliefs in spite of contrary evidence
Onset of Schizophrenia
spike at adolescence
F - second spike at 40s
Genetics and Schizophrenia
Large factor
less genetic overlap in dizygotic (~17%) that monozygotic (~50%) twins, less risk of developing Schizophrenia
Prevalence of Schizophrenia
1 in 100 people have
60x more than muscular dystrophy
6x more than insulin dependent diabetes
5x more than MS
2x more than Alzhimer’s
Dimensions of Schizophrenia
Positive symptoms
Negative symptoms
Cognitive symptoms
Positive Symptoms
Psychosis
- Hallucinations
- Delusions
- Disorganized thoughts and speech
- Bizarre behaviors
Negative Symptoms
Emotional Dysregulation
- lack of emotional expression
- reduced facial expression (flat affect)
- Inability to experience pleasure in everyday activities (anhedonia)
Impaired Motivation
- Reduced conversation (alogia)
- Diminished ability to begin or sustain activates
- Social withdraw
Cognitive Symptoms
Neurocognitive impairment
- Memory problems
- Poor attention span
- Difficulty making plans
- Reduced decision making capacity
- Poor social cognition
- Abnormal movement patterns
Auditory hallucinations
Many sounds
“Dementor Like”
All directed at individual/ speaking to
Early Development
Altered dopamine development
Childhood
Subtle behavioral changes can be detected (often in retrospect)
Prodrome
Adolescence
precedes diagnosis, abnormalities become clear
Disease Onset
when diagnosed
large increase in positive symptoms
Treatment
medication more effective with positive symptoms
can stabilize both positive and negative symptoms
(larger decrease in positive symptoms)
Diverse symptoms of Schizophrenia
different interpretations
many disorders with same symptoms
- need to break down individual symptoms to find underlying mechanism(s) via endophenotypes
Endophenotypes
quantifiable (sub-type) phenotypes also symptoms (not as broad) connect genetic and environmental factors
Simple deffinaition - Biomarker
Can be overlap - want to segregate with disease
Hierarchy of Endophenotype pyramid
Aetiological factors (genetic)
Putative brain abnormalities
Candidate endophenotypes
Behaviors
General - Syndrome, Endophenotypes, Genome
Endophenotypes of Schizophrenia
1) Reduction in pre pulse inhabitation
2) Gaze tracking Jerk
Clear differences that can be detected before diagnosis
Can be overlap - want to segregate with disease - even with family members that dont have symptoms can detect - potental to determine the underlying mechanism for schizophrenia
Pre Pulse Inhabitation
reduction in startle
Pre pulse is a signal given before a stimulus
Gaze tracking
visual tracking
follow moving cursor - much “jerker” than normal
Differences is Gating
both sensory and sensitometer
Normal - only perceive small subset of stimuli
Schizophrenia - Not efficient/ fragmented filtering to stimuli, “core symptoms” of cognitive fragmentation and functional disorganization
DISC1
Disrupted in Schizophrenia 1
Protine normaly regulates traficking of molecules within neurons
in family - everyone with Schizophrenia has mutation (however not everyone with mutation has Schizophrenia)
prevalence of mutation has large overlap with other psychiatric disorders.
Changes caused by DISC1
- Neuronal migration
- Signal pathway regulation
- Dendritic spine regulation
- Synaptic maintenance
Schizophrenia is a ____ disorder
neurodevelopmental
Particular nature of Schizophrenia
is still unclear
Primary hypothesis of Schizophrenia
- Excessive excitatory pruning
- Reduction in interneuron inhibitory activity in prefrontal cortex
- Myelination is delayed
Gray mater and Schizophrenia
Accelerated rate of loss of gray matter during adolescence
particularly 1) parietal frontal lobe 2) temporal lobe 3) Occipital lobe
Environment & Genetic factors in Schizophrenia
Increase in environmental and inc. in genetic, higher likelihood to develop Schizophrenia
Levels of Schizophrenia disability
no disorder
to “middle” - Schizotypy (more environment) - Schizophrenia Spectrum disorder (More genetic)
Schizophrenic
Environmental factors in Schizophrenia
- Place/time of birth
- Infection
- Prenatal (mother)
- Obstetric (during birth)
- Family History - Most important
Neuroanatomical differences with Schizophrenia
Increase in ventricle size (especially lateral ventricle)
decrease in surrounding area - especially the hippocampus
Hippocampus in Schizophrenia
forms one of the walls of the lateral ventricle
is decreased in size
cells are disorganized
Hypofrontality hypothesis in Schizophrenia
Decrease in frontal lobe activity both at rest and during tasks
Cocaine and Meth & Schizophrenia
causes an increase in dopamine Can precipitate (trigger) symptoms of Schizophrenia
Typical Neuroleptics
Support dopamine hypothesis
High affinity for D2 receptors
Are antagonists
Dopamine hypothesis of Schizophrenia
Higher level of dopamine or dopamine receptors
Overstimulation of cells
Atypical neuroleptics
have higher affinity for serotonin receptors
less likely to have motor effects
moderate affinity for D2 highest affinity for seritonin (5-HT2A)
PCP and Schizophrenia
Phencyclidine (PCP)
causes similar symptoms (Pos and Neg) - prolonged use causes prolonged pscychotic states NMDA antagonist (blocks NMDA central calcium chanel)- blocks glutamate
Glutamate hypothesis of Schizophrenia
decrease in glutamate and/or defect in glutamate receptor
Seen by PCP symptoms
__% of US population so ill that they are unable to cary our major life activites
4%
First rank symptoms of Schizophrenia
- audatory halusanations
- highly personalized delusions
- changes in affect (emotion)
Concordance
sharing of a characteristic
Fathered by ___ men, higher chance devoloping Schizophrenia
older, sperm have gon through more cell divisions, more oppurtunity to acumulate mutations
City vs Rural in Schizophrenia
living in city makes it much more likely (growing up in)
unsure if this is due to exposure to other ddieases, crowds, tense socal interactions, etc.
Individuals with larger lateral ventricles
bennifit less from antipsychotic medication
Chlorpromazine
Thorazine
Reduce positive symptoms
Amphetamine Psychosis
strickingly simillar to Schizophrenia, reversed with antipsychotic medication
LSD & Schizophrenia
Does not produce a Schizophrenia-like state
Effects of LSD are primaraly visual (rather than audatory)
Clinicaly effective does for first gen antipsychotics
can be reliabaly predicted from its affinity for D2 receptors
Clozapine
second gen antipsychotic
moderate affinity for D2 highest affinity for seritonin (5-HT2A)
Can increase dopa in frontal cortex
Supplamenting antipsychotics with ___ helps reduce symptoms
L-dopa (increasing dopaminergic activity)
Recovery in Schizophrenia with and without medicaton
longer recovery without medication
Psychotomimetic
A drug that induced a state resembeling Schizophrenia
Ketamine
similar effects at PCP
NMDA antagonist
Excitatory synapses
devolop first (around 5 years old)
Inhibatory start around 12
