ORIGINAL ARTICLE Rene´ Hurlemann Christian Boy Philipp T. Meyer Harald Scherk Michael Wagner Hans Herzog Heinz H. Coenen Kai Vogeley Peter Falkai Karl Zilles Wolfgang Maier Andreas Bauer Decreased prefrontal 5-HT 2A receptor binding in subjects at enhanced risk for schizophrenia Published online: 27 September 2005 Ó Springer-Verlag 2005 Abstract The brain serotonin-2A receptor (5-HT 2A R) has been implicated in both the pathology of schizo- phrenia and the therapeutic action of atypical antipsy- chotics. However, little is known about the 5-HT 2A R status before the onset of schizophrenia and before the exposure to antipsychotics. We used [ 18 F] altanserin and positron emission tomography (PET) in a pilot study of 6 individuals suspected to be at elevated risk for schizophrenia and seven age-matched controls to test the hypothesis that regional 5-HT 2A R binding is altered in the prodromal stages of schizophrenia. Distribution volume ratios (DVRs) as a proxy for 5-HT 2A R avail- ability were significantly reduced in prefrontal cortex regions of at-risk subjects, implicating early abnormali- ties of serotonergic neurotransmission that antecede the onset of schizophrenia. Keywords Serotonin-2A [(18)F]Altanserin PET At-risk Psychosis Schizophrenia Abbreviations DVR: distribution volume ratio ROI: region of interest at-risk: subjects with prodromal states for schizophrenia Introduction Neurochemical hypotheses of schizophrenia propose a role of the brain 5-HT 2A R in both the pathology of the disease and the therapeutic action of atypical antipsy- chotics (Dean 2003). Transmission of susceptibility for schizophrenia has been linked to allele 2 of the T102C polymorphism of the 5-HT 2A R gene (Erdmann et al. 1996; Williams et al. 1996; Abdolmaleky et al. 2004). Substantial evidence indicates a direct role of the pre- frontal 5-HT 2A R in the cognitive process of working memory (Williams et al. 2002), dysfunction of which is a core deficit in schizophrenia (Fletcher et al. 1998; Cam- eron et al. 2002). Most research on post-mortem brain tissue converges on locating a decrease of 5-HT 2A R binding in the prefrontal cortex of schizophrenic patients (e.g., Arora and Meltzer 1991; Laruelle et al. 1993; but see also Joyce et al. 1993). However, no consensus has evolved on the 5-HT 2A R in vivo status in schizophrenia. There are four [ 18 F]setoperone PET reports of either no specific alterations (Trichard et al. 1998; Lewis et al. 1999; Verhoeff et al. 2000) or significant decreases in prefrontal 5-HT 2A R binding (Ngan et al. 2000). The prodromal state is defined as that period pre- ceding the onset of schizophrenia, when there is increasing symptomatic presentation and functional deterioration (McGorry et al. 2000; Phillips et al. 2000; Klosterkotter et al. 2001; Ruhrmann et al. 2003; Hafner et al. 2004). Imaging the brain 5-HT 2A R during the prodromal stages provides an opportunity to identify potential abnormalities of serotonergic neurotransmis- R. Hurlemann (&) H. Scherk M. Wagner P. Falkai W. Maier K. Vogeley Department of Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany E-mail: Rene.Hurlemann@ukb.uni-bonn.de Tel.: +49-228-2871359 Fax: +49-228-2876097 R. Hurlemann C. Boy P. T. Meyer H. Herzog K. Vogeley K. Zilles A. Bauer Brain Imaging Center West, Institute of Medicine, Research Center Ju¨lich, Ju¨lich, Germany H. H. Coenen Institute of Nuclear Chemistry, Research Center Ju¨lich, Ju¨lich, Germany H. Scherk P. Falkai Department of Psychiatry, Saarland University Hospital, Homburg/Saar, Germany K. Zilles C. O. Vogt Institute for Brain Research, University of Duesseldorf, Duesseldorf, Germany Anat Embryol (2005) 210: 519–523 DOI 10.1007/s00429-005-0036-2