neuroimaging in psychiatry [email protected]
TRANSCRIPT
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Neuroimaging in Psychiatry [email protected]
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Imaging Modalities • Molecular Imaging (SPECT, PET) • MRI (structural, fMRI, DTI, spectroscopy) • Optical imaging • EEG, MEG • None are currently used to diagnose or help
prognosis of individual patients with psychiatric illness.
• All are useful in research, with group level studies, and some have helped in treatment development
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Summary points • PET imaging has helped to establish the most
effective medication dosing strategies • Imaging could, it is hoped, lead to earlier
diagnoses - eg in Dementia. • Neuroimaging can help inform our models of
healthy psychology and of psychiatric disorder, and may provide a rational basis for various interventions
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In-vivo molecular imaging
�The purpose of molecular imaging is to improve understanding of biology and medicine through non-invasive in vivo investigation of cellular molecular events involved in normal and pathologic processes� {Society of Molecular Imaging}
Currently clinical molecular imaging is mainly PET and SPECT!PET!
SPECT!SPECT!
I
O
ON
HO
* *A critical and rate limiting factor is the
development of imaging tracers [probes]!
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The Techniques: 1. PET
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SPECT or PET can measure the global pattern of functional loss by mapping blood flow or glucose metabolic rate
Non-selective molecular imaging
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By use of novel ligands that �bind� to specific molecular targets PET and SPECT can probe more selective abnormalities in patients with AD.
I
O
ON
HO
* *
[R,R]-123I-QNB is a selective ligand that binds with high affinity and selectivity to acetylcholine muscarinic receptors!
Selective molecular imaging:Radiochemistry
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Dopamine D2 Receptors are Lower in Addiction!
DA
D2
Rec
epto
r Ava
ilabi
lity!
control! addicted!
Cocaine!
Heroin!
Alcohol!
DA!
DA!
DA!
DA! DA !DA !
DA!
Reward Circuits!
DA !DA ! DA !DA !
DA !
Reward Circuits!
DA!
DA!
DA!
DA! DA !
DA!
Drug Abuser!
Non-Drug Abuser!
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Cause or Consequence of Drug use?
Impulsive rat, liable to addiction
Rat not liable to addiction Dalley et al 2007
Science
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For most first episode patients, 2mg haloperidol provided 65% D2 occupancy.
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Effect of amphetamine (0.3 mg/kg) on [123I]IBZM binding in healthy controls and untreated patients with schizophrenia. The y axis shows the percentage decrease in [123I]IBZM binding potential induced by amphetamine, which is a measure of the increased occupancy of D2 receptors by DA following the challenge. Laruelle et al 1996 PNAS
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Occupancy 2 studies
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MRI
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The fore-runner of structural MRI…
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But take care with confounders
See Ho et al 2011, Lewis et al 2011, Archives of General Psychiatry for discussions
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Further (clinical) pros and cons of imaging
• Most treatments involves medicines, and most MRI doesn�t measure chemicals
• But …
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How do antidepressants work?
• By dampening brain activity to negative self-descriptors? – Simplicio, Norbury & Harmer, Molecular
Psychiatry 2012
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Murray, Corlett… Fletcher 2008
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Amphetamine results similar to psychosis patient results
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Summary points • PET imaging has helped to establish the most
effective medication dosing strategies • Neuroimaging can help inform our models of
healthy psychology and of psychiatric disorder, and may provide a rational basis for various interventions