Introduction To Translational Psychiatry Flashcards
Understand abnormal structure and function in psychiatric disease Understand brain neurotransmitter systems
How does the ICD-10 and WHO define a mental disoder?
“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”
Name some of the most common psychiatric disorders
Schizophrenia and other psychoses
Mood disorders
Anxiety disorders
ACD
Addictions
Dementias
ADHD
Adult personality disorders
What are positive symptoms in Schizophrenia?
Hallucinations and delusions
What is a hallucination?
And what forms are commonly experienced in Schizophrenia?
Perception in the absence of an external stimulus
With the qualities of a real perception
Auditory (common), visual (uncommon)
What are delusions?
Belief held with conviction, despite evidence to the contrary, and out of keeping with a sociocultural background
Obsessions and eccentric ideas are not delusions
How does the ICD-10 criteria classify Schizophrenia?
At least one month of symptoms
- at least one ‘list 1’ symptom
- at least two ‘list 2’ symptoms
What are the ICD-10 ‘list 1’ symptoms of schizophrenia?
(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’
What are the ICD-10 ‘list 2’ symptoms for Schizophrenia?
(a) Persistent hallucinations in any modality
(b) Thought disorder
(c) catatonic behaviour
(d) negative symptoms
‘Planned decisions create nuts’
What is the ICD-10 criteria for diagnosing Unipolar depression?
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
What criteria must be met for Somatic Syndrome to be presen in unipolar depression?
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
What are some of the dimensional measures for psychiatric diseases, to measure syndrome severity ?
Depression - MADRA, 17 Hamilton, BDI
Psychosis - PANSS
Alcohol misuse - AUDIT
Is Anxiety part of Unipolar depression?
Linked pathologies
Usually mutually inclusive, directly proportional severities
How does fMRI measure brain activity?
Measures blood flow
Blood flow correlates with metabolic O2 demand
Used as an indirect measure of locational activity
What functions, and abnormalities are the ACC (anterior cingulate cortex) and AFC (orbitofrontal cortex) linked to?
Limbic, motivation
Mood disorder, schizophrenia, addictions
What functions, and abnormalities are the Basal Ganglia, including nucleus accumbens linked to?
Limbic, motivation
mood disorders, schizophrenia, addictions
What functions, and abnormalities are the brainstem, including VTA, PAG, DRN linked to?
Dopamine an dserotonin systems
Mood disorder, schizophrenia
What is the functional influence on behaviour of the Lateral Habenula?
Inhibits brainstem dopamine reward systems
Sensitive to aversive stimuli
What abnormalities is the temporal lobe linked to?
Hallucinations
Amygdala / hippocampus linked to aversive stimuli
Mood disorders
What functions, and abnormalities is the DLPFC (dorsolateral prefrontal cortex) linked to?
Cognition, planning executive function
Inferior region linked to emotion
In regards to the cingulate, what did Bush et al 2000 influentially describe in meta-analysis?
Dissociation of function of at different parts.
Dorsal divison for congition
Anterior divison for emotion
In regards to the Cingulate, what did Steele JD and lowrie SM (2004) describe?
Overlappin boundaries between functional regions
Dorsal and superior lateral - cognitive
Rostral and inferior medial - emotion
(emotion on the R.I.M.)
Steele JD et al (2008) showed what treatment for treatment-resistant depression?
Anterior cingulotomy in ‘emotion’ region, not posteriorly
Is associated with long term recovery
in regards to the cingulate, Vogt (2014) described what?
aMCC (anterior mid-cingulate cortex) correlates with subjective unpleasantness
pACC (pregenual ant-cingulate cortex) correlates with reward, subjective state of pleasure
Gradin V et al (2014) showed what area of the basal ganglia is changed in opiate dependency?
The activity of the Nucleus Accumbens (NA) is blunted in patient suffering addiction of opiates
What is the funtion of, and what disorders are implicated by dopamine?
Prediction of rewards, motivation
Schizophrenia, addictions, mood disorder
What is the funtion of, and what disorders are implicated by serotonin?
Responses to aversive stimuli
Depression, anxiety
What is the funtion of, and what disorders are implicated by opioids?
Liking (in contrast to wanting), with mu receptors
heroin dependency, methadone maintenance
What is the funtion of, and what disorders are implicated by GABA?
Inhibits dopamine in brainstem
Anxiety and fear
Benzodiazepines and dependency
What disorders are implicated by ACh?
Nucleus basalis of Meynert degeneration in Alzheimer’s and Parkinson’s
What is the funtion of, and what disorders are implicated by Glutamate/glutamine?
Opponent to GABA
Addiction and rewards related to learning
Probably important in repeated alcohol withdrawals
What are the dopamine system nuclei, where are they located and what functions are they implicated in?
Hypothalamus
Midbrain
- Ventral tegmental Area (limbic projections)
- Substantia nigra pars compacta (motor)
Gradin V, Steele JD (2011) describe what change in the dopamine VTA in depression?
Reduced activity in the VTA in depression
Reduced reward signalling
What are the serotonin system nuclei and where are they located / project to?
Raphe Nuclei of the brain stem
Dorsal nucleus
Median Nucleus
Project to the hippocampus, amygdala, cortex
Deaken JFW et al (2013) proposed an influential theory linking serotonin to what functions and behaviours?
Linked serotonin to:
Aversive experiences
Depressive illness
What are the three prinicple calsses of opiod receptor?
Mu - linked to pleasure (morphine agonises)
Kappa
Delta
What are the ACh system nuclei and where are they located / project to?
Basal forebrain (substantia inominata) - Nucleus basalis of Meynert
Medial septal nuclei
Brainstem - pontomesencephalo-tegmental complex
Project widely to brain
What are the requirements for a good candidate biomarker in psychiatry?
Objective measurement
Good sensitivity and specificity
May or may not be mechanism related
What are the types of biomarker possible from neuroimaging?
Diagnostic
- Sensitivity
- Specificity in comparison with competing diagnosis
Prognostic
-Likelihood or response to treatment A versus B
Risk
-Likelihood of developing a disorder
Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders.
Interpret this in Depression
Depressive Illness - anhedonia
Redcued value of rewards
Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders.
Interpret this in Schizophrenia/psychosis
Schizophrenia / psychosis - Delusional beliefs
Delusions associated with abnormal increased value
Decreased value of non-psychotic content
Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders.
Interpret this in addictions
Abnormally increased value of given drug of dependency
Decreased value of non-drug stimuli / self-neglect
Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders.
Interpret this for the use of psychopharmacology
Effective medications act on putatively abnormal neural valuation systems?
Treatment resistance reflects failure of this effect
What methods can be used to explore the neural valuation of Reinforement learning
Intrumental and pavlovian learning
Decision making tasts during fMRI
Computational neuroscience models of value estimation
What methods can be used to explore neural valuation in the context to neuroeconomics?
Operationalised social interaction
-Facilitates measurments of slippery intuitive social concepts (eg. trust)
Valuation and utility core concepts
Reinforcement learning. Describe the process of Classical (pavlovian) conditioning
Signal
Followed by reward/punishment
‘emotional learning’
Reinforcement learning. Describe the process of Instrumental (operative) conditioning
Two signals given (predictors)
Descision made (behavioural response)
Reward / punishment
‘states produced by instumental reinforcing stimuli’
How does Neural signalling reflect learning in conditioning? (eg. of dopamine neurones)
Increased firing if rewards > predicted
Reduced firing if rewards < predicted
No change in firing if reward delivery as predicted
In 2011, what did Gradin and Steele suggest evidence for in “Expected value and prediction error abnormalities in Depression and Schizophrenia”
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
Summaries the theory of Neural valuation in MDD and SZ
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
