L17 & 18 - Schizophrenia

Question 1

What is the history of schizophrenia?

Answer 1

Emil Kraepelin (1898):
- First described symptoms but called it dementia praecox
- Symptoms include impairments in attention, memory and goal directed behaviour (progressive)
Eugen Bleuler (1911):
- Reformulated dementia praecox and coined the term schizophrenia
- Fragmented thinking and positive and negative symptoms

Question 2

What is schizophrenia?

Answer 2

Syndrome that can have different causes
Positive symptoms - hallucinations, delusional, disorganised
Negative symptoms - lack of emotional expression, social withdrawal
Cognitive deficits - attentional dysfunctions, working memory, executive dysfunction

Question 3

What are the positive symptoms?

Answer 3

Delusions - false belief despite evidence to contrary, distorting reality patient beliefs someone is plotting against them, but also:
- thought insertion
- thought withdrawal
- thought broadcasting
- not being in control of own actions

Hallucinations - perceptual experience seems real in the absence of physical proof, seeing a person that is not real

Disorganized behaviour - can affect speech, difficulties with routine tasks, inappropriate emotions

Question 4

What are the negative symptoms?

Answer 4

Diminished emotional expression
- blunted affect, mood or emotional state, limited range of emotions
- Alogia = speech poverty, lack of conversation

Avolition
- apathy
- social withdrawal
- Anhedonia = inability to feel pleasure

Question 5

What are the cognitive deficits?

Answer 5

Substantial impairment in overall cognitive performance
Can be variable
Most common deficits in:
- executive functions/cognitive control (verbal fluency and problem solving)
- Attention
- Processing speed
- Memory
- Social cognition
Presence of cognitive deficits associated with poor daily functioning and quality of life
These are good predictors for the quality of life and daily functioning
No treatment for cognitive deficits

Question 6

When do symptoms start to show?

Answer 6

Pos/neg symptoms show during late adolescence
Cognitive deficits detectable in childhood/adolescence
Slow emergence of brain abnormalities

Question 7

What are the risk factors of schixophrenia?

Answer 7

Combination of genetics and environment (80% heritable)
- 1% people
- Children or siblings 10x more likely to develop SZ
- Polygenic disorder - 108 genes
- Genetics only explain small percent
Environmental risk:
- Adverse events prenatally or perinatally
- Hippocampal injuries in rats development of abnormal dopamine organisation
- Contact with viruses
- Growing up in an urban environment
- Air pollution
- Drugs

Question 7

What are the transmitters involved in SZ?

Answer 7

Dopamine
Acetylcholine
Glutamate - main excitatory
GABA - main inhibitory

Question 8

What is dopamine’s role in SZ?

Answer 8

Important role of mesocortical dopaminergic
DA agonists can induce psychotic symptoms
Disturbances in DA system impaired cognitive functions
Typical antipsychotic medication reduces DA levels in the brain
- reduce positive symptoms
- ineffective for negative and cognitive symptoms

Question 9

What is the dopamine hypothesis?

Answer 9

Dissociation: cortical vs striatal DA
- hypodopaminergic state in cortex
- hyperdopaminergic state in striatum
Too much dopamine in one place and too little in another
DA levels fluctuate in individuals with SZ over time, cognitive symptoms much more stable

Question 10

What is the role of glutamate?

Answer 10

Dysregulation of DA secondary to glutamate function
Post-mortem - loss of glu neurons in ACC
Moghaddam & Javitt 2012 - 2 phases of glu modulations
1. NMDA mediated interneuron dysfunction - loss of inhibitory control (increased glu levels)
2. Glu-induced excitotoxicity - loss of glu connection (decreased glu levels)

Question 11

What is a MRS?

Answer 11

Magnetic resonance spectroscopy
- measure neurometabolites in vivo

Question 12

What did Sydnor and Roalf 2020 find in SZ patients?

Answer 12

Meta-analysis of MRS studies in psychosis patients
Decreased glu in patients compared to controls

Question 13

What are the multiple systems that are affected?

Answer 13

Atypical antipsychotics target a variety of neurotransmitters: DA, serotonin, adrenalin
Neurotransmitter systems seem to be affected to differ degrees in patients which might explain
- variability in symptoms between patients
- why available drugs are not effective to same extent in all patients

Question 14

What are the neuroanatomical differences between SZ vs non SZ?

Answer 14

Brains of SZ patients weigh less than average weight
Enlarged ventricles
Reduced neuron numbers in prefrontal cortex
Thinner parahippocampal gyri
Abnormal cellular structure in prefrontal cortex and hippocampus
Reduced surrounding structure - different brain areas not as connected

Question 15

What was Liolia 2012 research into differences between SZ and non-SZ?

Answer 15

Meta-analysis investigated grey matter loss I individuals with SZ
In chronic SZ GM reduced in:
- medial prefrontal cortex, anterior cingulate cortex
- insular cortex bilaterally
- left thalamus and caudate
amygdala bilaterally

Question 16

What are the problems with cognitive symptoms?

Answer 16

Comprise large range of different cognitive processes (executive functions, WM, language, episodic memory, processing speed, attention, inhibition, sensory processing)
- Difficult to understand underlying mechanisms
- Difficult to develop effective interventions

Question 17

What was Barch and Ceaser’s 2012 research into cognitive symptoms?

Answer 17

Common mechanism across cognitive domains - context processing, WM, and episodic memory
Impairment in representing goal information in WM to guide behaviour = impairment in proactive control
Proactive control associated with representation of information in dorsolateral prefrontal cortex

Question 18

Dual mechanisms of control?

Answer 18

Braver 2009
Goal in WM - action - action outcome - monitoring - needs for adjustment - adaption
Attentional
Learning
Motor
Responses

Question 19

What is the WM in SZ patients?

Answer 19

No general deficits but impairments in specific components
CE - associated with DLPFC in healthy patients, difficulty updating or maintaining information in SZ, reduced DLPFC
VSS, PL - no strong evidence, intact activity in these areas

Question 20

What is processing speed like in SZ patients?

Answer 20

Meta-analysis (Dickinson 2007) showed impairments
Digit symbol coding type task
Slowed processing speed in patients might be due to lack of integrity of white matter fibre tracts

Question 21

What is episodic memory like in SZ patients?

Answer 21

Relational memory more impaired than item memory
Associated with DLPFC activity
Rehearsal condition (item memory) - remember the order of items on the screen
Reorder condition (relational memory) - re arrange items according to weight, from lightest to heaviest
Recollection more impaired than familiarity during remembering - remembering exactly where in what context one has seen something
Familiarity - feeling of knowing
Encoding items in relation to their context is disrupted in SZ

Question 22

What are the motivational impairments in SZ?

Answer 22

Affects social and occupational functioning
No effective treatments
Underlying mechanisms not clear
Culbreth - atypical effort based decision making may contribute to motivational impairments
Effort based decision making - estimation of physical/mental effort to reach certain outcome
SZ less willing to exert effort

Question 23

What is the physical and mental efforts for decision making in SZ?

Answer 23

Experiments requiring participants to make repeated decisions between doing a hard or easy task to gain a high/low amount of money
SZ less likely to select hard task compared to control
Correlation with negative symptoms: those with more severe negative symptoms are least willing to exert more effort

Question 24

What are the neural correlateS of effort based decision making?

Answer 24

Structures involved in effort based decision making in healthy individuals
- medial frontal cortex
- ventral striatum
- dopamine systems
BOLD activity in ventral striatum and anterior cingulate cortex correlated with action value e.g. increasing with reward value, decreasing with effort
SZ - reduced BOLD activity during effort based decisions

Question 25

What is situation as a factor influencing effort based decision making?

Answer 25

Situation - considers the reward, probability to receive the reward, considers effort, precision of effort estimation, motivational state

Question 26

What is reward positivity as a factor influencing effort based decision making?

Answer 26

Reward positivity - How much do they enjoy the reward? SZ show reduced reward responsivity, less likely to exert effort - fit with negative symptoms - but self report measures did not differ from controls ?

Question 27

What is anticipatory pleasure as a factor influencing effort-based decision making?

Answer 27

How good will the reward be?
Will lead to more effort
SZ show reduced anticipatory pleasure
Correlations between anticipatory pleasure and effort in patients, if reported more anticipatory pleasure expended more effort

Question 27

What is cognitive control as a factor influencing effort based decision making?

Answer 27

Effort based decision making required several functions that depend on intact cognitive control
- integrating decision information
- utilising representations of costs and reward
SZ associated with reduced DLPFC

Question 28

What is defeatist performance beliefs as a factor influencing effort based decision making?

Answer 28

SZ often have negative beliefs about ability
If they don’t think they are good at baking they won’t bake cookies
Biased decisions against putting effort into a task

Question 29

What is dopaminergic medication as a factor influencing effort based decision making?

Answer 29

Decision making is associated with striatal dopamine
Antipsychotics block dopaminergic receptor sites, might modulate activity in brain areas involved in effort based decision making
- only small sample size and correlation cofounded with negative symptoms