74. The Neurochemical Basis of Antipsychotic Response in Psychosis: A Prospective Multimodal 18 F-Dopa and 1-H MRS Study in First-Episode Psychosis.

摘要

>Background: Antipsychotic medication remains the primary treatment for symptoms of psychosis. The dopamine system, in particular, the presynaptic system, has been linked to treatment response, leading to the suggestion that dopaminergic and nondopaminergic forms of schizophrenia exist. This has been examined in vivo, using PET to index presynaptic dopamine (linking elevated dopamine to good treatment response), and Magnetic Resonance Spectroscopy (MRS) to measure glutamatergic function, linking elevated anterior cingulate glutamate to poor antipsychotic response. To date, no study has utilised these measures to examine antipsychotic response prospectively, in first episode patients. We sought to examine both neuroimaging methods in antipsychotic-naïve, first-episode psychosis patients, before and after treatment. >Methods: 18F-DOPA PET and 1-H MRS study, in people witfirst episode psychosis, naive of antipsychotic medication, those minimally treated with antipsychotic medication (for less than 2 weeks) and those not taking antipsychotic medication.Baseline and follow-up whole striatum Kicer, anterior cingulate glutamate and baseline and follow-up PANSS after antipsychotic treatment >Results: There was a significant positive correlation between baseline Kicer and subsequent improvement in PANSS positive (rho =0.64, P < .01), negative (rho=0.48, P = .03), total symptoms (rho=0.56, P = .01) and GAF score (rho=0.54,. There was no relationship between glutamate levels and any clinical measure. There was a significant effect of group on Kicer (F(2,25)=5.73, P < .01). Kicer was significantly higher in responders than both non-responders (P = .03) and healthy volunteers (P < .01). Cohen’s d effect size for the elevation in the responders relative to nonresponders was 1.28. No difference in dopamine synthesis capacity was found after treatment for at least 4 weeks of antipsychotic medication, t (20) = 0.73, P = 0.49. A positive correlation was found between change in dopamine synthesis capacity and change in PANSS positive symptoms (Pearson’s r = .47, P = .04), though not PANSS negative (r = .4, P = .1) or total symptoms (r = .42, P = .08). >Conclusion: Dopamine, and not glutamate function, predicts the response to antipsychotic treatment. Change in dopamine synthesis capacity is related to positive symptom change. Variability exists in the effects of antipsychotic medication on presynaptic dopamine function.