Relationship between dopamine D 2 receptor occupancy, clinical response, and drug and monoamine metabolites levels in plasma and cerebrospinal fluid. A pilot study in patients suffering from first-episode schizophrenia treated with quetiapine Georg Nikisch a, * , Pierre Baumann g , Bernhard Kießling a,1 , Michael Reinert d,4 , Georg Wiedemann a,1 , Jan Kehr h,7 , Aleksander A. Mathé f,6 , Markus Piel e,5 , Frank Roesch e,5 , Heike Weisser c,3 , Peter Schneider d,4 , Andreas Hertel b,2 a Department of Psychiatry and Psychotherapy, Klinikum Fulda gAG, Pacelliallee 4, 36043 Fulda, Germany b Department of Nuclear Medicine, Klinikum Fulda gAG, Pacelliallee 4, 36043 Fulda, Germany c Department of Medical Laboratory, Klinikum Fulda gAG, Pacelliallee 4, 36043 Fulda, Germany d Department of Medical Physics and Radiation Protection, Klinikum Fulda gAG, Pacelliallee 4, 36043 Fulda, Germany e Institute for Nuclear Chemistry, University of Mainz, Fritz-Straßmann-Weg 2, 55128 Mainz, Germany f Karolinska Institutet, Clinical Neuroscience, Psychiatry M56, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden g Department of Psychiatry, CHUV, Hospital of Cery, 1008 Prilly-Lausanne, Switzerland h Karolinska Institutet, Department of Physiology and Pharmacology, 17177 Stockholm, Sweden article info Article history: Received 15 October 2009 Received in revised form 1 February 2010 Accepted 2 February 2010 Keywords: Schizophrenia Quetiapine Norquetiapine CSF Monoamine metabolites Neuroimaging abstract Combining measurements of the monoamine metabolites in the cerebrospinal fluid (CSF) and neuroim- aging can increase efficiency of drug discovery for treatment of brain disorders. To address this question, we examined five drug-naïve patients suffering from schizophrenic disorder. Patients were assessed clin- ically, using the Positive and Negative Syndrome Scale (PANSS): at baseline and then at weekly intervals. Plasma and CSF levels of quetiapine and norquetiapine as well CSF 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindole-acetic acid (5-HIAA) and 3-methoxy-4-hydroxyphe- nylglycol (MHPG) were obtained at baseline and again after at least a 4 week medication trail with 600 mg/day quetiapine. CSF monoamine metabolites levels were compared with dopamine D 2 receptor occupancy (DA-D 2 ) using [ 18 F]fallypride and positron emission tomography (PET). Quetiapine produced preferential occupancy of parietal cortex vs. putamenal DA-D 2 , 41.4% (p < 0.05, corrected for multiple comparisons). DA-D 2 receptor occupancies in the occipital and parietal cortex were correlated with CSF quetiapine and norquetiapine levels (p< 0.01 and p< 0.05, respectively). CSF monoamine metabolites were significantly increased after treatment and correlated with regional receptor occupancies in the putamen [DOPAC: (p < 0.01) and HVA: (p < 0.05)], caudate nucleus [HVA: (p < 0.01)], thalamus [MHPG: (p < 0.05)] and in the temporal cortex [HVA: (p < 0.05) and 5-HIAA: (p < 0.05)]. This suggests that CSF monoamine metabolites levels reflect the effects of quetiapine treatment on neurotransmitters in vivo and indicates that monitoring plasma and CSF quetiapine and norquetiapine levels may be of clinical relevance. Ó 2010 Elsevier Ltd. All rights reserved. 0022-3956/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2010.02.004 * Corresponding author. E-mail addresses: georg.nikisch@klinikum-fulda.de (G. Nikisch), pierre.baumann@chuv.ch (P. Baumann), kiessling.bernhard@klinikum-fulda.de (B. Kießling), Michael.- Reinert.Radiologie@klinikum-fulda.de (M. Reinert), psychiatrie@klinikum-fulda.de (G. Wiedemann), jan.kehr@ki.se (J. Kehr), aleksander.mathe@ki.se (A.A. Mathé), piel@uni- mainz.de (M. Piel), frank.roesch@uni-mainz.de (F. Roesch), heike.weisser@klinikum-fulda.de (H. Weisser), p.schneider@klinikum-fulda.de (P. Schneider), AHertel.RAZ@kli- nikum-fulda.de (A. Hertel). 1 Tel.: +49 661 84 5736; fax: +49 661 84 5722. 2 Tel.: +49 661 84 6330; fax: +49 661 84 6332. 3 Tel.: +49 661 84 6370; fax: +49 661 84 6372. 4 Tel.: +49 661 84 6310; fax: +49 661 84 6312. 5 Tel.: +49 6131 39 25371; fax: +49 6131 39 25253. 6 Tel.: +46 70 4840743; fax: +46 8 300972. 7 Tel.: +46 8 524 87084; fax: +46 8 300972. Journal of Psychiatric Research 44 (2010) 754–759 Contents lists available at ScienceDirect Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/jpsychires RETRACTED