1. By Rahul Kapoor

2. Based on a study performed by Stephen McGowan MRCPsych Andrew D. LawrenceMRCPsych Tim Sales MRCPsych Digby Quested MRCPsych Paul Grasby MRCPsych Performed at Hammersmith Hospital, Imperial college, London

3. Introduction Objective – Assessment of presynaptic dopaminergic fuction in a group of patients suffering from Schizophrenia by means of fluorodopa uptake and PET scanning Patients – 16 male medicated outpatients with DSM IV daignosis of schizophrenia and 12 age matched patients free of psychiatric and neurologic disorders Main outcome measure – fluorodaopa (FD) uptake constant measures and region of interest analysis Results and conclusion – in the end

4. Introduction (contd) Dopamine (DA) overactivity hypothesis still remains to be fully confirmed or refuted. Multiple causes for DA synthesis  increases synthesis, release, receptor number, affinity etc. Most imaging studies have confirmed the DA receptor changes in schizophrenia Prefrontal D1 receptors reported to be increased, decreased or unchanged in the illness Increase in striatal D2 receptors (smaller magnitude than in the reported post mortem changes) Evidence of increased DA release has been shown in the recent studies (laurelle et al and Brier et al)

5. Fluorodopa Radioactive analogue of L-dopa (precursor for dopamine) FD – taken up by presynaptic monoaminergic neurons where it is metabolized to fluorodopamine (enzyme = aromatic acid decarboxylase/AADC) Flourodopamine is trapped and stored within the vesicles in the nerve terminals FD uptake can be measured as influx constant (Ki) can be used to measure AADC activity and vesicular storage capacity High values of fluorodopa observed in areas of dense DA nerve terminal innervation (e.g. striatum) Fluorodopa – extinsively used in the assessment of straiatal dopaminergic neurons specially in Parkinson’s disease and other movement disorders

6. Patients 12 right handed healthy individuals as volunteers (mean age = 38.3 years) 20 patients meeting DSM IV criteria for schizophrenia (mran age = 39.9 years) EXCLUSION  4 patients were excluded : 1 patient had bilateral perisylvian atrophy on MRI in 1 patient, there were technical problems with PET 2 patients had excessive head movement during PET

7. Data analysis 2 methods used  i) statistical parametric mapping (SPM) ii) Region of interest approach (ROI) SPM – template of FD uptake created using combined images of FD and T1 MR images. ROI- data analyzed by means of standardized ROIs on representative single participant image available in T1 MRI

8. Results SPM analysis – increases in FD uptake (Ki) in the striatum of patients compared with controls ; increased FD predominantly in ventral striatum Using ROIs – Ki values in the whole striatum and the ventral striatum were increased in patients compared to controls (supporting the SPM analysis) FD uptake in ROI not significantly correlated with the presence of positive or negative symptoms (scores) Structural MRI imaging – no volume differences in the striatal volumes between the controls and the patients (whether assessed as a whole or ventral or dorsal separately)

9. Conclusion The increased Ki (uptake of FD) by the schizophrenic patients confirms that presynaptic striatal dopamine dysfunction is present, predominantly being in the ventral striatum.

10. Thank you for your attention