PET Application in Psychiatry

PET Application in Psychiatry

Ramin V. Parsey and J. John MannRamin V. Parsey and J. John Mann

By Dan Diner

PETPET nuclear medical imaging technique Produces 3D images(maps) of functional

processes in the body Scientists inject short half-life radioactive

isotopes(tracers) into body, then detect gamma rays

nuclear medical imaging technique Produces 3D images(maps) of functional

processes in the body Scientists inject short half-life radioactive

isotopes(tracers) into body, then detect gamma rays

isotope goes through positron decay emits a positron(antimatter of electron) Travels a few mm and annihilates with an

electron, producing gamma photons moving in opposite directions*

The annihilation is detected by the scintillator material in the scanning device, which sends off a burst of light that is caught by the photomultiplier tubes

isotope goes through positron decay emits a positron(antimatter of electron) Travels a few mm and annihilates with an

electron, producing gamma photons moving in opposite directions*

The annihilation is detected by the scintillator material in the scanning device, which sends off a burst of light that is caught by the photomultiplier tubes

[15O]-Water[15O]-Water

Half-life of 2 minutes Used to image blood flow Use of it also indicated pre-frontal cortex

deficit in depression

Half-life of 2 minutes Used to image blood flow Use of it also indicated pre-frontal cortex

deficit in depression

18F-FDG(fluoro-2-deoxyglucose)

18F-FDG(fluoro-2-deoxyglucose)

used for the assessment of glucose activity in brain (and heart). Used for finding tumors.

Patients fast 6 hours beforehand After injection, patient waits 1 hour Taken in by tissues with high metabolic activities- such

as tumors High for tumors because not they don’t listen to body.

Grow out of control. More Cells. Patient does keeps physical activity to a minimum so as

to minimize uptake of radioactive chemicals into muscles

used for the assessment of glucose activity in brain (and heart). Used for finding tumors.

Patients fast 6 hours beforehand After injection, patient waits 1 hour Taken in by tissues with high metabolic activities- such

as tumors High for tumors because not they don’t listen to body.

Grow out of control. More Cells. Patient does keeps physical activity to a minimum so as

to minimize uptake of radioactive chemicals into muscles

Neuroimaging studies generally agree that mood disorders link with functional deficits but disagreed about structal deficits:

Study with depressed patients found 11/12 had low regional cerebral metabolic rate of glucose

Other studies studies claim that differences in key brain region volumes play roles in mood disorders

Neuroimaging studies generally agree that mood disorders link with functional deficits but disagreed about structal deficits:

Study with depressed patients found 11/12 had low regional cerebral metabolic rate of glucose

Other studies studies claim that differences in key brain region volumes play roles in mood disorders

SerotoninSerotonin

Neurotransmitter in CNS Regulates anger, sleep, body temperature,

aggression, mood, appetite, vomiting, and sexuality

Deficits in Serotonin are associated with extreme mood disorders, such as Obsessive Compulsive Disorder, bipolar disorder, and clinical depression

Neurotransmitter in CNS Regulates anger, sleep, body temperature,

aggression, mood, appetite, vomiting, and sexuality

Deficits in Serotonin are associated with extreme mood disorders, such as Obsessive Compulsive Disorder, bipolar disorder, and clinical depression

Cont.Cont. Abnormal 5-HT transmission is thought to cause

major depression In postmortem studies, less serotonin transorter

binding was found throughout the dorsal(upper)-ventral extent of the prefrontal cortex and in the brainstem of people with episodes of major depression

Found lower 5-HT transporter binding in midbrain, amygdala, and ventral striatum, but not the thalamus

Abnormal 5-HT transmission is thought to cause major depression

In postmortem studies, less serotonin transorter binding was found throughout the dorsal(upper)-ventral extent of the prefrontal cortex and in the brainstem of people with episodes of major depression

Found lower 5-HT transporter binding in midbrain, amygdala, and ventral striatum, but not the thalamus

The lab found that depressed people's prefrontal cortex responds poorly to forced brain activity using serotonin

this suggests that pre-frontal cortex might be malfunctioning in depressed people

Fenfluramine(drug) was used as the challenge. It is supposed to activate brain activity everywhere in the brain

The lab found that depressed people's prefrontal cortex responds poorly to forced brain activity using serotonin

this suggests that pre-frontal cortex might be malfunctioning in depressed people

Fenfluramine(drug) was used as the challenge. It is supposed to activate brain activity everywhere in the brain

Why?Why?Hypotheses: Low 5-HT transporter binding could be due

to a functional change in the distribution of transporters

few serotonin nerve terminals due to fewer 5-HT neurons

Fewer terminals or fewer transporters per terminals

Hypotheses: Low 5-HT transporter binding could be due

to a functional change in the distribution of transporters

few serotonin nerve terminals due to fewer 5-HT neurons

Fewer terminals or fewer transporters per terminals

This is a PET McNeil scan result. McNeil binds to the serotonintransporter

(A) is an MRI (B) is a healthy person pet scan (C) is a depressed person

This is a PET McNeil scan result. McNeil binds to the serotonintransporter

(A) is an MRI (B) is a healthy person pet scan (C) is a depressed person

Notice that regions in a depressed person have much less serotonin transporterThis suggests that the serotonin system is different between healthy and depressed people. Future drugs could be made to stabilize this system.

SchizophreniaSchizophrenia

Mental disorder characterized by an impaired perception of reality

Often patients have hallucinogens Hypothesized to be caused by abnormal

Dopamine levels PET scan is often used to understand why

Mental disorder characterized by an impaired perception of reality

Often patients have hallucinogens Hypothesized to be caused by abnormal

Dopamine levels PET scan is often used to understand why

Dopamine System in Schizophrenia

Dopamine System in Schizophrenia

Dopamine- a neurotransmitter released by the hypothalamus that is also used as a medication that increases heart rate and blood pressure

Studies using [11C]-raclopride showed no result in D2 receptor binding abnormalities

but studies using [11C]-N-methyl-spiper-one showed that schizophrenics tended to have more D2 receptor binding

[11C]-raclopride have been used for same general purpose, and showed that decrease in [11C]-raclopride binding was proportional to amount of dopamine released

Dopamine- a neurotransmitter released by the hypothalamus that is also used as a medication that increases heart rate and blood pressure

Studies using [11C]-raclopride showed no result in D2 receptor binding abnormalities

but studies using [11C]-N-methyl-spiper-one showed that schizophrenics tended to have more D2 receptor binding

[11C]-raclopride have been used for same general purpose, and showed that decrease in [11C]-raclopride binding was proportional to amount of dopamine released

Psychotropic Drug DevelopmentPsychotropic Drug Development

[11C]-raclopride has been used to show that typical/classical antipsychotics (e.g. haloperidol) block over 70-80% of D2 receptors at doses with therapeutic effects. Atypical/newer generation antipsychotic block <70%. Atypical antidepressants produce much less side effects.

[11C]-raclopride has been used to show that typical/classical antipsychotics (e.g. haloperidol) block over 70-80% of D2 receptors at doses with therapeutic effects. Atypical/newer generation antipsychotic block <70%. Atypical antidepressants produce much less side effects.

Cont.Cont.

Antidepressants that enhance serotonin function(such as SSRI’s(Selective serotonin reuptake inhibitors)) have a therapeutic effects that evolve for weeks

SSRI prevents neurotransmitter from going back to the pre-synaptic neuron(reuptake)

Antidepressants that enhance serotonin function(such as SSRI’s(Selective serotonin reuptake inhibitors)) have a therapeutic effects that evolve for weeks

SSRI prevents neurotransmitter from going back to the pre-synaptic neuron(reuptake)

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