Lecture 7 - Introduction to Schiz Flashcards
Outline Falvet 1851 on discovery schizophrenia
Falvet circulaire Circular madness Extremes highs and lows mood Looked isolation Distinguish subtypes
Outline Hecker 1871 on discovery schizophrenia
Hebephrenia First describe Schiz symptoms Early onset Deteriorating over time Problems emotion Sub types symptoms
Outline Emil Kraeplin 1898 on discovery schizophrenia
Combined into single disease - dementia Praecox
Seeing psychiatric diseases biological
Dissecting brains
First describe illness progressive no return
How does Kraeplin 1898 describe dementia
Global disruption of perceptual and cognitive processes
How does Kraeplin 1898 describe Praecox
Early adulthood onset
Who coined the term dementia Praecox
Emil Kraeplin 1898
Outline Eugen Bleuler 1911 on discovery schizophrenia
Reformulated dementia Praecox
Coined term schizophrenia
Characterised: fragmented thinking, breakdown of integrated functions coordinate affect and behaviour
Disturbances of association primary symptoms of Schiz
Who coined the term schizophrenia
Eugen Bleuler 1911
What did Bleuler 1911 identify as primary symptoms of Schiz
Disturbances of association
What does Bleuler 1911 believe schizophrenia Stands for
Schizo = split
Phrene = mind
What are Bleuler 1911 4 As
4 elements understand symptoms
Association
Ambivalence
Autism
Aspesticity
Outline Positive Type 1 symptoms of Schiz by Tim Crow 1980
Delusions
Hallucinations
Thought disorders
Outline Negative Type 2 symptoms of Schiz by Tim Crow 1980
Anhedonia
Flattened affect
Avolition
Alogia
Outline cognitive symptoms of Schiz by Tim Crow 1980
Working memory
Executive dysfunction
Attentional deficits
Outline delusions as positive symptoms of Schiz
False belief despite evidence contrary
Outline Bizarre delusions as positive symptoms of schizophrenia
Bizarre delusion = thought insertion withdrawal thought broadcasting made actions
Outline examples of delusions as positive symptoms of schiz
Persecutory Paranoid Control Grandiose Reference
Outline hallucinations as positive symptoms of Schiz
Perceptual experience real in absence physical proof
Most common auditory visual olfactory
Outline thought disorders as positive symptoms of Schiz
Inventing words
Trouble understanding common words
Changing topic
Outline negative symptoms of Schiz
Blunted affect
Mood or emotional state
Limited range emotions
Anhedonia: inability to feel pleasure
Outline cognitive thought symptoms of Schiz
Avolition - unable begin tasks lack motivation
Alogia - unable speak
Problems working memory planning learning
Problematic - prevent joining workforce
What did Peter Liddle 1987 conduct
Re examined positive negative dichotomy
Included 3rd factor disorganisation Syndrome - attributed to positive dimension
What 3 Syndrome categories did Liddle 1987 identify
Psychomotor poverty
Reality distortion
Disorganisation Syndrome
Define Psychomotor Poverty by Liddle 1987
Poverty of speech
Decreased spontaneous movement
Blunted affect
Define Reality Distortion by Liddle 1987
Delusions
Hallucinations
Define Disorganisation Syndrome by Liddle 1987
Inappropriate affect
Distractibility
Poverty of content of speech
Thought disturbances
What 5 factors did Liddle expand to in 2002
- Psychomotor poverty
- Reality distortion
- Disorganisation
- Psychomotor excitation
- Anxiety/Depression
Developed world what are the 4 leading causes lost year of healthy life aged 15-44
- Major depressive disorders
- Alcohol use
- Road traffic accidents
- Schizophrenia
What are the cognitive symptoms a target for
Applied research
Drug companies
What did Fletcher and Frith 2009 identify as voices in the head
Audible thoughts - after own thought head another voice. Embodied
Voices arguing
Voices commenting on actions
Influence on body - somatic positivity
What did Fletcher and Frith 2009 identify as thoughts in the head
Thoughts of withdrawal
Inserting
Broadcasting
Delusional perception
What did Fletcher and Frith 2009 identify as “made”
Made feelings
Impulses
Volitional acts - delusions of control
Outline enlarged ventricles in twins with Schiz
Structural physical change
Replicated
Maguire - hippocampal size increased London taxi drivers.
Physical difference not always due to illness can be down to experience
Criticisms of enlarged ventricles in Schiz
Other causes not specific to Schiz
Brain plasticity
Must ppts medicated being tested
If not medicated often unusual condition
What studies investigate frontal cortex brain activation during executive tasks in Schiz
N back task
Haying task
Outline the N back Task
Asked press key if target letter appears
Then if the target letter is same as 1 letter before press key
Same as 2 letters before etc
Go back increases load on working memory
Outline results N Back task
Activation across frontal cortex
Activation lower in Schiz
Outline Haying Task
Test Inhibition
Given part of sentence
Asked to complete sentence by providing an extra word
Results of Haying Task
Activation across Frontal Cortex Brain
Activation lower in Schiz
How can we correct for medication use in studies
See if higher doses produce higher effects than lower doses
If they do probably effect of medication
Outline fMRI study looking at the activation of the brain whilst people are hallucinating
Ppts press button when felt hallucinations coming on
Experiencing hallucinations as if they are real activating specific brain regions
Outline early and late gray matter deficits in Schiz by Thompson et al 2001
Loss gray matter as disease progresses
Down to long term drug use
Different social environments, being treated differently, don’t have a job
Outline Bressler and Menon 2009 faulty connectivity in Schiz Ventral Medial PFC -> PCC
Default mode. Endogenous mediated. Self referential mental activity
Deactivated doing cognitively engaging demanding tasks
Activated social tasks
Self monitoring - know where things are coming from
Abnormality - disruption tell where things coming from
Outline Bressler and Menon 2009 faulty connectivity in Schiz Salience Network AI -> ACC
Dynamic switching
Associated emotion
VTA = reward
Orientation most salient things in environment
Outline Bressler and Menon 2009 faulty connectivity in Schiz Central Executive Network
Dorsal Lateral PFC -> PPC
Exogenously drive
Cognitively demanding mental activity
Switching between activities = WM loaded
Faulty connectivity leads positive symptoms
What is the % of general population getting Schiz
1
What is the likelihood of getting Schiz if your identical twin has it
48
What is the likelihood of getting Schiz if your fraternal twin has it
17
What is the likelihood of getting Schiz if your children has it
13
What is the likelihood of getting Schiz if your siblings have it
9
What is the likelihood of getting Schiz if your parents have it
6
What are the approaches to investigating the neurochemistry of Schiz
- Post Mortem studies
- Peripheral markers
- Mechanism of action of antipsychotic drugs - animals and humans radioactive labelling
- In vivo receptor binding PET Scan
Outline the dopamine theory of Schiz
Overactivity in brain dopamine transmission
Hyperactivity Mesolimbic dopamine rise to positive symptoms
Hyperactivity frontal cortex rise negative
How does the effectivity of antipsychotic drugs parallel support the dopamine theory of Schiz
Effective antipsychotics parallels their pharmacological potency in blocking dopamine binding
How does the dopamine theory account for the role of Amphetamine
Amphetamine which releases dopamine
Induces psychosis
Responds to neuroleptics
What is the link between the Dopamine Theory and Parkinson’s
Parkinson’s is a side effect of neuroleptic
Reduce dopamine in striation
Restricting movement of body
Develop Parkinson’s
Outline post mortem study support for the dopamine theory of Schiz
Receptor affinity studies increased D2 but not D1 receptors in striatum
Mixed results D4 receptors - 6 fold in Schiz others no D4 receptors
Outline Abi Darghone et al increases striatal dopamine transmission support of dopamine Theory
Binding in PET Compounds displace amphetamine Give amphetamine binds to dopamine Greater effect those with Schiz Hyperactivity dopamine System in Schiz
Outline the dopamine systems
VTA - thalamus areas and cortex - pre frontal region
Substantia Nigra region - extremely involved motor behaviour
Blocked causes motor side effects
Outline Howes et al 2009 elevated striata dopamine function linked to Prodromal signs of Schiz
High people Schiz signs coming on but not yet developed
Measuring dopamine function through displacement activity in PET scanning
ARMS - at risk mental state
Outline Metabolite Measurements - Peripheral Markers
Brain DA turnover reflected by plasma Homovanillic acid concentrations
Chronic antipsychotic treatment lowers plasma HVA related good treatment outcomes
Outline In Vivo Methods Animal Studies
Mesolimbic dopamine System implicates animal models of disrupted selective attention in Schiz
Latent Inhibition
Pre pulses Inhibition
Outline In Vivo Methods Animal Studies findings on antipsychotics
Chronic antipsychotic decrease dopamine firing A9 naac and A10 striatum
Chronic atypic antipsychotics decrease firing in A10
Outline animal models of Schiz
Selective attentional models be disrupted by augmentation of dopamine function
Latent Inhibition disrupted by amphetamine - reversed by antipsychotic drugs: Haloperidol clozapine
Outline D-amphetamine abolishing latent Inhibition
Amphetamine disruption still occur when absence of dopamine but not for locomotor activity
Creates hyperactive state reliant D2 receptor
But locomotor activity is not - other neuromechanisms involved
Outline In Vivo Methods of Patient Studies
In vivo methods of D2 receptors affinity in humans using PET scanning
Increase D2 binding no change in other studies
Reasons discrepancies: specificity of ligands and patient populations
What is the neurochemistry of Glutamate and Schiz
Drugs block glutamate receptors such as PCP
Produce psychosis
What is the neurochemistry of Serotonin and Schiz
Atypical antipsychotic drugs high affinity for 5-HT2 receptor
Via modularity role on DA function
What is the neurochemistry of GABA and Schiz
Modulators role on DA function
Outline abnormalities of NMDA and Kainate receptors of Schiz and glutamate
Abnormalities NMDA and Kainate receptors in Schiz prefrontal cortex
Associated up regulation of NR1 subunit
Outline decrease in glutamate synthesis and Schiz
Decrease glutamate synthesis release in cortex
Decrease certain receptor sites for glutamate in certain areas brain
Such as
Cingulate and hippocampus
Links between cognitive deficits glutamate and Schiz
Cog deficits consequence reductions in transcript mRNA for receptor subunits NMDAR1 GLUR1 GLUR7 KA1 In frontal cortex
Links between glutamate PCP and Schiz
PCP induces psychosis
Is a non competitive NMDA antagonist
