Altered 5-HT(2A) receptor binding after recovery from bulimia-type anorexia nervosa: relationships to harm avoidance and drive for thinness

Abstract

Several lines of evidence suggest that a disturbance of serotonin neuronal pathways may contribute to the pathogenesis of anorexia nervosa (AN) and bulimia nervosa (BN). This study applied positron emission tomography (PET) to investigate the brain serotonin 2A (5-HT(2A)) receptor, which could contribute to disturbances of appetite and behavior in AN and BN. To avoid the confounding effects of malnutrition, we studied 10 women recovered from bulimia-type AN (REC AN-BN, > 1 year normal weight, regular menstrual cycles, no binging, or purging) compared with 16 healthy control women (CW) using PET imaging and a specific 5-HT(2A) receptor antagonist, [18F]altanserin. REC AN-BN women had significantly reduced [18F]altanserin binding potential relative to CW in the left subgenual cingulate, the left parietal cortex, and the right occipital cortex. [18F]altanserin binding potential was positively related to harm avoidance and negatively related to novelty seeking in cingulate and temporal regions only in REC AN-BN subjects. In addition, REC AN-BN had negative relationships between [18F]altanserin binding potential and drive for thinness in several cortical regions. In conclusion, this study extends research suggesting that altered 5-HT neuronal system activity persists after recovery from bulimia-type AN, particularly in subgenual cingulate regions. Altered 5-HT neurotransmission after recovery also supports the possibility that this may be a trait-related disturbance that contributes to the pathophysiology of eating disorders. It is possible that subgenual cingulate findings are not specific for AN-BN, but may be related to the high incidence of lifetime major depressive disorder diagnosis in these subjects.

Figure 1

(a) Horizontal sections from coregistered SPGR magnetic resonance (upper panel) and positron emission tomography (PET; lower panel) images of a typical subject recovered from anorexia nervosa, bulimic type. The PET images are summations of dynamic data acquired over 12–90 min after [¹⁸F]altanserin injection. The PET and MR imaging sections on the left include the left and right parietal cortex (BA 7), whereas those on the right include the subgenual cingulate (BA 25, inferior to the genu of the corpus callosum). Also shown are examples of the regions-of-interest that were used to generate the PET time–activity data. (b) Examples of the [¹⁸F]altanserin PET time–activity data that were generated for the parietal and subgenual cingulate cortices and cerebellum of the subject described above (a). The inset graph shows the early kinetics of the time–activity data (0–5 min postinjection). Similar curve shapes were observed for the two cortical regions-of-interest, whereas lower uptake and rapid clearance was observed in the cerebellum.

Figure 2

(a) Correlation of Harm avoidance, subscale 2, and [¹⁸F]altanserin binding potential (ALT BP) in the right mesial temporal cortex. rho, Pearson’s correlation coefficient. (b) Correlation of Eating Disorder Inventory-2 (EDI-2), subscale ‘drive for thinness’ and [¹⁸F]altanserin binding potential (ALT BP) in the left parietal cortex. rho, Pearson’s correlation coefficient.