In vivo evidence of global and focal brain alterations in anorexia nervosa Andrea Boghi a, ⁎, Sara Sterpone b , Stefano Sales c , Federico D'Agata d , Gianni Boris Bradac c , Giuseppina Zullo b , Donato Munno b a Section of Neuroradiology, Department of Radiodiagnostics, S. Croce Hospital, Cuneo, Italy b Clinical Psychology Service, Psychiatry Section, Department of Neuroscience, University of Torino, Italy c Neuroradiology, Department of Neuroscience, University of Torino, Italy d Department of Psychology, University of Torino, Italy abstract article info Article history: Received 8 July 2009 Received in revised form 26 November 2010 Accepted 11 December 2010 Keywords: Neuroimaging Voxel-based morphometry Eating disorder Caudate nucleus Hypothalamus Cerebellum Brain alterations are known to be associated with anorexia nervosa (AN) and tend to be distributed across brain structures, with only a few reports describing focal damage. Magnetic resonance images of 21 anorexic patients with different disease duration and 27 control subjects were acquired and compared using voxel- based morphometry (VBM). Patients had a significant reduction of total white matter (WM) volume and focal gray matter (GM) atrophy in cerebellum, hypothalamus, caudate nucleus and frontal, parietal and temporal areas. The cerebellum was more affected in patients with longer disease duration, whereas the hypothalamic alterations were more pronounced in patients with shorter food restriction. A correlation with body mass index (BMI) and GM was found in the hypothalamus. Our data demonstrate a diffuse reduction of WM together with focal areas of GM atrophy in AN. The finding of a hypothalamic focal atrophy points to hormonal dysfunction and opens the possibility for a central dysregulation of homeostasis. The involvement of temporoparietal areas could account for body image distortion. Finally, the cerebellar GM atrophy confirms previous findings and seems to be a late consequence of AN that could play a role in the chronic phase of the disease. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Anorexia nervosa (AN) is an eating disorder (ED) that predom- inantly affects women from adolescence to adulthood (sex ratio: 10/1=F/M); its incidence and lifetime prevalence among females are 0.5-1% and 0.5%, respectively (DSM IV-TR, American Psychiatric Association, 2000). Clinical features of AN are body image distortion and intense fear of becoming fat, with refusal of food and consequent severe emaciation (Cash and Deagle, 1997; Epstein et al., 2001; Seeger et al., 2002; Wagner et al., 2003). Because of self-starvation, anorexic patients could suffer from several physical consequences, such as anemia, osteoporosis, amenorrhea and other endocrine dysfunctions. Notably, cerebral alterations have been described as among these consequences. Cerebral alterations relative to controls have been demonstrated in post mortem investigations (Gagel, 1953; Martin, 1958) and in vivo by neuroimaging studies, using computed tomography (CT) (Enzmann and Lane, 1977; Kolhmeyer et al., 1983; Artmann et al., 1985; Dolan et al., 1988; Hoffman et al., 1989; Addolorato et al., 1998) and magnetic resonance imaging (MRI) (Golden et al., 1996; Katzman et al., 1996; Kingston et al., 1996; Swayze et al., 1996, 2003; Lambe et al., 1997; Inui et al., 2002; Miwa et al., 2004). The most frequently described macroscopic anatomical brain changes are cerebral and cerebellar gray matter (GM) and white matter (WM) atrophy and ventricular enlargement. These findings have been globally distributed over the brain, suggesting a diffuse cerebral vulnerability. However atrophy has also been reported in some discrete areas, including paracentral lobule (Inui et al., 2002), thalamus, midbrain (Husain et al., 1992), mammillary bodies (King- ston et al., 1996) and extra-striate body areas (Suchan et al., 2010). On the other hand, some authors have failed to find significant total and focal GM volumetric differences between anorexics and healthy controls (Swayze et al., 1996, 2003). The inconsistency in findings can partly be explained by the reversibility of these lesions. Indeed, longitudinal studies have reported that both GM and WM abnormalities are partially reversible after body weight restoration (GM: Kingston et al., 1996; Katzman et al., 1997; Swayze et al., 1996, 2003; WM: Swayze et al., 2003). Similar results have been reported for intracranial cerebrospinal fluid (CSF) volume. It has been found to be increased in the supratentorial ventricular compartments (Artmann et al., 1985; Kingston et al., 1996) and in the subarachnoid spaces (Krieg et al., Psychiatry Research: Neuroimaging 192 (2011) 154–159 ⁎ Corresponding author. Section of Neuroradiology, Department of Radiodiagnostics, S. Croce Hospital, Via M. Coppino 26, 12100, Cuneo, Italy. Tel.: + 39 0171 641082; fax: +39 0171 641090. E-mail address: boghi.a@ospedale.cuneo.it (A. Boghi). 0925-4927/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pscychresns.2010.12.008 Contents lists available at ScienceDirect Psychiatry Research: Neuroimaging journal homepage: www.elsevier.com/locate/psychresns