Brain Serotonin 1A Receptor Binding in Bulimia Nervosa Jari Tiihonen, Anna Keski-Rahkonen, Mari Lo ¨ ppo ¨ nen, Maria Muhonen, Jaana Kajander, Topias Allonen, Kjell Na ˚gren, Jarmo Hietala, and Aila Rissanen Background: Selective serotonin reuptake inhibitors (SSRIs) are the first choice for the pharmacologic treatment of bulimia nervosa, but there are no published data on the putative altered serotonin (5-HT) receptor characteristics in patients with bulimia. Experimental studies suggest that the therapeutic antidepressant effect of SSRIs is mediated via 5-HT 1A receptors. The aim of this study was to measure brain 5-HT 1A receptor binding among nonmedicated patients with bulimia nervosa. Methods: Positron emission tomography (PET) with a selective 5-HT 1A ligand, [ 11 C]WAY-100635, was performed on eight unmedicated patients with bulimia and 10 healthy comparison subjects. Results: The binding potential values were greater in patients than in control subjects in all brain regions studied. The most robust differences were observed in the angular gyrus, the medial prefrontal cortex, and the posterior cingulate cortex. Conclusions: These results suggest that brain 5-HT 1A receptor binding is increased in several cortical areas in patients with bulimia nervosa during their state of impulsive binge eating. Key Words: Bulimia, serotonin, receptor, positron emission tomog- raphy (PET), 5-HT 1A , brain B ulimia nervosa is characterized by recurrent binge-eating episodes and loss of self-control over eating (First et al 1997). Bulimic eating is associated with altered serotonin (5-HT) neurotransmission (Fairburn and Harrison 2003). Two recent studies suggest that brain 5-HT transporter availability is reduced in bulimic and binge-eating patients compared with control subjects (Kuikka et al 2001; Tauscher et al 2001), and reduced 5-HT 2A binding has been reported among patients who have recovered from bulimia (Kaye et al 2001); however, there are no published data on 5-HT receptor characteristics in patients with current bulimic symptoms. Selective serotonin reuptake inhibitors (SSRIs) are the first choice of pharmacologic treatment for bulimia (Fairburn and Harrison 2003), and experimental studies suggest that the therapeutic effect of SSRIs is actually mediated via the 5-HT 1A receptors (Blier et al 1990; Ramboz et al 1998). The aim of the present study was to test the hypothesis that brain 5-HT 1A receptor binding is altered among patients with bulimia nervosa. Methods and Materials Participants Eight right-handed nonpregnant women (mean age 25.8 years, range 20 –31) with a current DSM-IV diagnosis of bulimia nervosa were included in the study. None had a history of anorexia, and seven had binge–purge behavior at least once per week. The duration of bulimic symptoms ranged from 12 to 180 months (mean  SD, 71.2  85.5). The body mass index (BMI) of these patients was 21.1  1.8 kg/m 2 , and the Bulimic Investigatory Test, Edinburgh severity score was 12.3  3.4 (Henderson and Freeman 1987). The psychiatric diagnoses were set in accordance with DSM-IV criteria (First et al 1997), and patients with current psychosis, major depressive disorder, and cluster A or B personality disorders were excluded. One of the patients had a coexisting panic disorder and obsessive-compul- sive personality disorder. Five patients had never received psychotropic medication, and three had been free of medication for more than 3 months before the study. Owing to irregular menstrual cycling or the use of contraceptives among patients, it was not possible to match or standardize the phase of the menstrual cycles between the groups. Ten healthy age- and weight-matched right-handed women (mean age 24.9 years, range 20 –33) served as control subjects. The BMI of the control subjects was 22.9  3.2 kg/m 2 . All subjects gave their written informed consent before participation in this study. The study protocol was approved by the Ethics Board of the Helsinki University Hospital. PET Imaging The women were studied with positron emission tomography (PET) (GE Advance, three-dimensional mode; General Electric Medical Systems, Milwaukee, Wisconsin) and [carbonyl- 11 C]WAY-100635 (235  59 MBq) with arterial plasma input (Oikonen et al 2000). The specific radioactivity at the time of tracer administration was 124  68 GBq/mol (injected tracer mass 1.08  .68 g). Cortical regions and cerebellar cortex were defined on coregistered magnetic resonance images (MRIs). The PET-MRI image alignment was done with a surface-fitting pro- cedure (Pellizari et al 1989). The region of interest analysis was exploratory and focused primarily on frontal and temporal cortex and raphe. Dorsal raphe was identified in the PET images. The brain 5-HT 1A receptor binding potential (referring to k3/k4 in this article) was calculated with an indirect kinetic analysis, with arterial input function as the primary analysis (Parsey et al 2000). Arterial input data were not available for one control subject and one patient owing to technical problems during blood sampling. From the Departments of Psychiatry (JT, AK-R, ML, MM, AR) and Public Health (AK-R), University of Helsinki; Helsinki University Hospital (JT, AK-R, ML, MM, AR), Helsinki; Department of Forensic Psychiatry (JT), University of Kuopio, Niuvanniemi Hospital; Department of Clinical Physiology (JT), Kuopio University Hospital, Kuopio; Turku Positron Emis- sion Tomography Centre (JK, TA, KN, JH), Turku University Central Hos- pital; and Department of Psychiatry (JH), University of Turku, Finland. Address reprint requests to Jari Tiihonen, M.D., Ph.D., University of Kuopio, Niuvanniemi Hospital, Department of Forensic Psychiatry, Kuopio FIN- 70240, Finland. Received September 8, 2003; revised December 18, 2003; accepted December 19, 2003. BIOL PSYCHIATRY 2004;55:871– 873 0006-3223/04/$30.00 doi:10.1016/j.biopsych.2003.12.016 © 2004 Society of Biological Psychiatry