Introduction To Translational Psychiatry

Question 1

How does the ICD-10 and WHO define a mental disoder?

Answer 1

“Mental disorder is not an exact term, but implies the existence of a clinically recognisable set of symptoms and behaviours associated in most cases with distress and with interference with personal functions”

Question 2

Name some of the most common psychiatric disorders

Answer 2

Schizophrenia and other psychoses

Mood disorders

Anxiety disorders

ACD

Addictions

Dementias

ADHD

Adult personality disorders

Question 3

What are positive symptoms in Schizophrenia?

Answer 3

Hallucinations and delusions

Question 4

What is a hallucination?

And what forms are commonly experienced in Schizophrenia?

Answer 4

Perception in the absence of an external stimulus

With the qualities of a real perception

Auditory (common), visual (uncommon)

Question 5

What are delusions?

Answer 5

Belief held with conviction, despite evidence to the contrary, and out of keeping with a sociocultural background

Obsessions and eccentric ideas are not delusions

Question 6

How does the ICD-10 criteria classify Schizophrenia?

Answer 6

At least one month of symptoms

• at least one ‘list 1’ symptom
• at least two ‘list 2’ symptoms

Question 7

What are the ICD-10 ‘list 1’ symptoms of schizophrenia?

Answer 7

(a) Thought echo, insertion, withdrawal or broadcasting
(b) Delusions of control, influence or passivity
(c) Third person auditory hallucinations
(d) Persistent delusional beliefs

‘The Cats Tickle Ducks’

Question 8

What are the ICD-10 ‘list 2’ symptoms for Schizophrenia?

Answer 8

(a) Persistent hallucinations in any modality
(b) Thought disorder
(c) catatonic behaviour
(d) negative symptoms

‘Planned decisions create nuts’

Question 9

What is the ICD-10 criteria for diagnosing Unipolar depression?

Answer 9

2 weeks

two of:

• Depressed mood
• Anhedonia
• Decreased energy

one of:

• loss of self-esteem
• inappropriate guilt
• thoughts of death / suicide
• Poor concentration
• Agitation / retardation
• Sleep disturbance
• Change in appetite

Question 10

What criteria must be met for Somatic Syndrome to be presen in unipolar depression?

Answer 10

Four of:

• Anhedonia
• Emotional blunting
• Early morning waking
• Dinural variation (worse a.m.)
• Psychomotor agitation / retardation

Loss of apetite

Weight loss (>5%)

Loss of libido

Question 11

What are some of the dimensional measures for psychiatric diseases, to measure syndrome severity ?

Answer 11

Depression - MADRA, 17 Hamilton, BDI

Psychosis - PANSS

Alcohol misuse - AUDIT

Question 12

Is Anxiety part of Unipolar depression?

Answer 12

Linked pathologies

Usually mutually inclusive, directly proportional severities

Question 13

How does fMRI measure brain activity?

Answer 13

Measures blood flow

Blood flow correlates with metabolic O2 demand

Used as an indirect measure of locational activity

Question 14

What functions, and abnormalities are the ACC (anterior cingulate cortex) and AFC (orbitofrontal cortex) linked to?

Answer 14

Limbic, motivation

Mood disorder, schizophrenia, addictions

Question 15

What functions, and abnormalities are the Basal Ganglia, including nucleus accumbens linked to?

Answer 15

Limbic, motivation

mood disorders, schizophrenia, addictions

Question 16

What functions, and abnormalities are the brainstem, including VTA, PAG, DRN linked to?

Answer 16

Dopamine an dserotonin systems

Mood disorder, schizophrenia

Question 17

What is the functional influence on behaviour of the Lateral Habenula?

Answer 17

Inhibits brainstem dopamine reward systems

Sensitive to aversive stimuli

Question 18

What abnormalities is the temporal lobe linked to?

Answer 18

Hallucinations

Amygdala / hippocampus linked to aversive stimuli

Mood disorders

Question 19

What functions, and abnormalities is the DLPFC (dorsolateral prefrontal cortex) linked to?

Answer 19

Cognition, planning executive function

Inferior region linked to emotion

Question 20

In regards to the cingulate, what did Bush et al 2000 influentially describe in meta-analysis?

Answer 20

Dissociation of function of at different parts.

Dorsal divison for congition

Anterior divison for emotion

Question 21

In regards to the Cingulate, what did Steele JD and lowrie SM (2004) describe?

Answer 21

Overlappin boundaries between functional regions

Dorsal and superior lateral - cognitive

Rostral and inferior medial - emotion

(emotion on the R.I.M.)

Question 22

Steele JD et al (2008) showed what treatment for treatment-resistant depression?

Answer 22

Anterior cingulotomy in ‘emotion’ region, not posteriorly

Is associated with long term recovery

Question 23

in regards to the cingulate, Vogt (2014) described what?

Answer 23

aMCC (anterior mid-cingulate cortex) correlates with subjective unpleasantness

pACC (pregenual ant-cingulate cortex) correlates with reward, subjective state of pleasure

Question 24

Gradin V et al (2014) showed what area of the basal ganglia is changed in opiate dependency?

Answer 24

The activity of the Nucleus Accumbens (NA) is blunted in patient suffering addiction of opiates

Question 25

What is the funtion of, and what disorders are implicated by dopamine?

Answer 25

Prediction of rewards, motivation Schizophrenia, addictions, mood disorder

Question 26

What is the funtion of, and what disorders are implicated by serotonin?

Answer 26

Responses to aversive stimuli Depression, anxiety

Question 27

What is the funtion of, and what disorders are implicated by opioids?

Answer 27

Liking (in contrast to wanting), with mu receptors heroin dependency, methadone maintenance

Question 28

What is the funtion of, and what disorders are implicated by GABA?

Answer 28

Inhibits dopamine in brainstem Anxiety and fear Benzodiazepines and dependency

Question 29

What disorders are implicated by ACh?

Answer 29

Nucleus basalis of Meynert degeneration in Alzheimer's and Parkinson's

Question 30

What is the funtion of, and what disorders are implicated by Glutamate/glutamine?

Answer 30

Opponent to GABA Addiction and rewards related to learning Probably important in repeated alcohol withdrawals

Question 31

What are the dopamine system nuclei, where are they located and what functions are they implicated in?

Answer 31

Hypothalamus Midbrain - Ventral tegmental Area (limbic projections) - Substantia nigra pars compacta (motor)

Question 32

Gradin V, Steele JD (2011) describe what change in the dopamine VTA in depression?

Answer 32

Reduced activity in the VTA in depression Reduced reward signalling

Question 33

What are the serotonin system nuclei and where are they located / project to?

Answer 33

Raphe Nuclei of the brain stem Dorsal nucleus Median Nucleus Project to the hippocampus, amygdala, cortex

Question 34

Deaken JFW et al (2013) proposed an influential theory linking serotonin to what functions and behaviours?

Answer 34

Linked serotonin to: Aversive experiences Depressive illness

Question 35

What are the three prinicple calsses of opiod receptor?

Answer 35

Mu - linked to pleasure (morphine agonises) Kappa Delta

Question 36

What are the ACh system nuclei and where are they located / project to?

Answer 36

Basal forebrain (substantia inominata) - Nucleus basalis of Meynert Medial septal nuclei Brainstem - pontomesencephalo-tegmental complex Project widely to brain

Question 37

What are the requirements for a good candidate biomarker in psychiatry?

Answer 37

Objective measurement Good sensitivity and specificity May or may not be mechanism related

Question 38

What are the types of biomarker possible from neuroimaging?

Answer 38

Diagnostic - Sensitivity - Specificity in comparison with competing diagnosis Prognostic -Likelihood or response to treatment A versus B Risk -Likelihood of developing a disorder

Question 39

Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders. Interpret this in Depression

Answer 39

Depressive Illness - anhedonia Redcued value of rewards

Question 40

Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders. Interpret this in Schizophrenia/psychosis

Answer 40

Schizophrenia / psychosis - Delusional beliefs Delusions associated with abnormal increased value Decreased value of non-psychotic content

Question 41

Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders. Interpret this in addictions

Answer 41

Abnormally increased value of given drug of dependency Decreased value of non-drug stimuli / self-neglect

Question 42

Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders. Interpret this for the use of psychopharmacology

Answer 42

Effective medications act on putatively abnormal neural valuation systems? Treatment resistance reflects failure of this effect

Question 43

What methods can be used to explore the neural valuation of Reinforement learning

Answer 43

Intrumental and pavlovian learning Decision making tasts during fMRI Computational neuroscience models of value estimation

Question 44

What methods can be used to explore neural valuation in the context to neuroeconomics?

Answer 44

Operationalised social interaction -Facilitates measurments of slippery intuitive social concepts (eg. trust) Valuation and utility core concepts

Question 45

Reinforcement learning. Describe the process of Classical (pavlovian) conditioning

Answer 45

Signal Followed by reward/punishment 'emotional learning'

Question 46

Reinforcement learning. Describe the process of Instrumental (operative) conditioning

Answer 46

Two signals given (predictors) Descision made (behavioural response) Reward / punishment 'states produced by instumental reinforcing stimuli'

Question 47

How does Neural signalling reflect learning in conditioning? (eg. of dopamine neurones)

Answer 47

Increased firing if rewards \> predicted Reduced firing if rewards \< predicted No change in firing if reward delivery as predicted

Question 48

In 2011, what did Gradin and Steele suggest evidence for in "Expected value and prediction error abnormalities in Depression and Schizophrenia"

Answer 48

Aim - Are depession and Schiz. associated with abnormal valuation? Prediction - abnormal decision and outcome times during instrumental learning Methods - Instumental learning paradigm + fMRI Result - MSS and SZ patients weaker/absent reward value encoding -SZ absence of value signaling correlated with increase in severity of delusions and hallucinations

Question 49

Summaries the theory of Neural valuation in MDD and SZ

Answer 49

MDD and SZ -Learning about reward stimuli unrelated to illness content Reduced encoding of reward values - Extent of reduction correlates with syndrome severity - DIfferent spatial pattern of abnormality between SZ and MDD