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Slide 1: PET Application in Psychiatry Ramin V. Parsey and J. John Mann By Dan Diner
Slide 2:  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 PET
Slide 3:  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
Slide 4: [15O]-Water  Half-life of 2 minutes  Used to image blood flow  Use of it also indicated pre-frontal cortex deficit in depression
Slide 5: F-FDG (fluoro-2-deoxyglucose) 18  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 activitiessuch 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
Slide 6:  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
Slide 7: Serotonin  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
Slide 8:  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 Cont.
Slide 9:  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
Slide 10: 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
Slide 11:  This is a PET McNeil scan result.  McNeil binds to the serotonin transporter  (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 transporter This suggests that the serotonin system is different between healthy and depressed people. Future drugs could be made to stabilize this system.
Slide 12: Schizophrenia  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
Slide 13: 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
Slide 15: Psychotropic 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.
Slide 16: 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)
Slide 17: END