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Neuropharmacology - Translational Psychiatry > Introduction To Translational Psychiatry > Flashcards

Introduction To Translational Psychiatry Flashcards

Understand abnormal structure and function in psychiatric disease Understand brain neurotransmitter systems

1
Q

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

A

“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”

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2
Q

Name some of the most common psychiatric disorders

A

Schizophrenia and other psychoses

Mood disorders

Anxiety disorders

ACD

Addictions

Dementias

ADHD

Adult personality disorders

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3
Q

What are positive symptoms in Schizophrenia?

A

Hallucinations and delusions

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4
Q

What is a hallucination?

And what forms are commonly experienced in Schizophrenia?

A

Perception in the absence of an external stimulus

With the qualities of a real perception

Auditory (common), visual (uncommon)

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5
Q

What are delusions?

A

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

Obsessions and eccentric ideas are not delusions

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6
Q

How does the ICD-10 criteria classify Schizophrenia?

A

At least one month of symptoms

  • at least one ‘list 1’ symptom
  • at least two ‘list 2’ symptoms
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7
Q

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

A

(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’

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8
Q

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

A

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

‘Planned decisions create nuts’

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9
Q

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

A

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
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10
Q

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

A

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

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11
Q

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

A

Depression - MADRA, 17 Hamilton, BDI

Psychosis - PANSS

Alcohol misuse - AUDIT

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12
Q

Is Anxiety part of Unipolar depression?

A

Linked pathologies

Usually mutually inclusive, directly proportional severities

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13
Q

How does fMRI measure brain activity?

A

Measures blood flow

Blood flow correlates with metabolic O2 demand

Used as an indirect measure of locational activity

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14
Q

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

A

Limbic, motivation

Mood disorder, schizophrenia, addictions

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15
Q

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

A

Limbic, motivation

mood disorders, schizophrenia, addictions

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16
Q

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

A

Dopamine an dserotonin systems

Mood disorder, schizophrenia

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17
Q

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

A

Inhibits brainstem dopamine reward systems

Sensitive to aversive stimuli

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18
Q

What abnormalities is the temporal lobe linked to?

A

Hallucinations

Amygdala / hippocampus linked to aversive stimuli

Mood disorders

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19
Q

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

A

Cognition, planning executive function

Inferior region linked to emotion

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20
Q

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

A

Dissociation of function of at different parts.

Dorsal divison for congition

Anterior divison for emotion

21
Q

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

A

Overlappin boundaries between functional regions

Dorsal and superior lateral - cognitive

Rostral and inferior medial - emotion

(emotion on the R.I.M.)

22
Q

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

A

Anterior cingulotomy in ‘emotion’ region, not posteriorly

Is associated with long term recovery

23
Q

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

A

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

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

24
Q

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

A

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

25
Q

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

A

Prediction of rewards, motivation

Schizophrenia, addictions, mood disorder

26
Q

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

A

Responses to aversive stimuli

Depression, anxiety

27
Q

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

A

Liking (in contrast to wanting), with mu receptors

heroin dependency, methadone maintenance

28
Q

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

A

Inhibits dopamine in brainstem

Anxiety and fear

Benzodiazepines and dependency

29
Q

What disorders are implicated by ACh?

A

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

30
Q

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

A

Opponent to GABA

Addiction and rewards related to learning

Probably important in repeated alcohol withdrawals

31
Q

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

A

Hypothalamus

Midbrain

  • Ventral tegmental Area (limbic projections)
  • Substantia nigra pars compacta (motor)
32
Q

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

A

Reduced activity in the VTA in depression

Reduced reward signalling

33
Q

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

A

Raphe Nuclei of the brain stem

Dorsal nucleus

Median Nucleus

Project to the hippocampus, amygdala, cortex

34
Q

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

A

Linked serotonin to:

Aversive experiences

Depressive illness

35
Q

What are the three prinicple calsses of opiod receptor?

A

Mu - linked to pleasure (morphine agonises)

Kappa

Delta

36
Q

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

A

Basal forebrain (substantia inominata) - Nucleus basalis of Meynert

Medial septal nuclei

Brainstem - pontomesencephalo-tegmental complex

Project widely to brain

37
Q

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

A

Objective measurement

Good sensitivity and specificity

May or may not be mechanism related

38
Q

What are the types of biomarker possible from neuroimaging?

A

Diagnostic

  • Sensitivity
  • Specificity in comparison with competing diagnosis

Prognostic

-Likelihood or response to treatment A versus B

Risk

-Likelihood of developing a disorder

39
Q

Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders.

Interpret this in Depression

A

Depressive Illness - anhedonia

Redcued value of rewards

40
Q

Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders.

Interpret this in Schizophrenia/psychosis

A

Schizophrenia / psychosis - Delusional beliefs

Delusions associated with abnormal increased value

Decreased value of non-psychotic content

41
Q

Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders.

Interpret this in addictions

A

Abnormally increased value of given drug of dependency

Decreased value of non-drug stimuli / self-neglect

42
Q

Detecting abnormalities of Neural value estimation can be used to reflect different psychiatirc disorders.

Interpret this for the use of psychopharmacology

A

Effective medications act on putatively abnormal neural valuation systems?

Treatment resistance reflects failure of this effect

43
Q

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

A

Intrumental and pavlovian learning

Decision making tasts during fMRI

Computational neuroscience models of value estimation

44
Q

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

A

Operationalised social interaction

-Facilitates measurments of slippery intuitive social concepts (eg. trust)

Valuation and utility core concepts

45
Q

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

A

Signal

Followed by reward/punishment

‘emotional learning’

46
Q

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

A

Two signals given (predictors)

Descision made (behavioural response)

Reward / punishment

‘states produced by instumental reinforcing stimuli’

47
Q

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

A

Increased firing if rewards > predicted

Reduced firing if rewards < predicted

No change in firing if reward delivery as predicted

48
Q

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

A

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

49
Q

Summaries the theory of Neural valuation in MDD and SZ

A

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

Neuropharmacology - Translational Psychiatry (12 decks)

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