altanserin and Anorexia-Nervosa

Many studies have found disturbances of serotonin (5-HT) activity in anorexia nervosa (AN). Because little is known about 5-HT receptor function in AN, positron emission tomography (PET) imaging with 5-HT receptor-specific radioligands was used to characterize 5-HT1A and 5-HT2A receptors.. Fifteen women ill with AN (ILL AN) were compared with 29 healthy control women (CW); PET and [11C]WAY100635 were used to assess binding potential (BP) of the 5-HT1A receptor, and [18F]altanserin was used to assess postsynaptic 5-HT2A receptor BP. [15O] water and PET were used to assess cerebral blood flow.. The ILL AN women had a highly significant (30%-70%) increase in [11C]WAY100635 BP in prefrontal and lateral orbital frontal regions, mesial and lateral temporal lobes, parietal cortex, and dorsal raphe nuclei compared with CW. The [18F]altanserin BP was normal in ILL AN but was positively and significantly related to harm avoidance in suprapragenual cingulate, frontal, and parietal regions. Cerebral blood flow was normal in ILL AN women.. Increased activity of 5-HT1A receptor activity may help explain poor response to 5-HT medication in ILL AN. This study extends data suggesting that 5-HT function, and, specifically, the 5-HT2A receptor, is related to anxiety in AN.

Topics: Adult; Anorexia Nervosa; Cerebrovascular Circulation; Data Interpretation, Statistical; Female; Humans; Ketanserin; Magnetic Resonance Imaging; Oxygen Radioisotopes; Piperazines; Positron-Emission Tomography; Pyridines; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2A; Serotonin Antagonists

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.

Topics: Adult; Age Factors; Anorexia Nervosa; Brain; Brain Mapping; Bulimia; Drive; Female; Fluorine Radioisotopes; Harm Reduction; Humans; Ketanserin; Protein Binding; Receptor, Serotonin, 5-HT2A; Serotonin 5-HT2 Receptor Antagonists; Thinness; Time Factors; Tomography, Emission-Computed

Several lines of evidence suggest that a disturbance of serotonin neuronal pathways may contribute to the pathogenesis of anorexia nervosa (AN). This study applied positron emission tomography (PET) to investigate the brain serotonin 2A (5HT2A) receptor, which could contribute to disturbances of appetite and behavior in AN.. To avoid the confounding effects of malnutrition, we studied 16 women recovered from AN (REC AN, >1 year normal weight, regular menstrual cycles, no bingeing or purging) compared with 23 healthy control women (CW) using [18F]altanserin, a specific 5-HT2A receptor antagonist on PET imaging.. REC AN women had significantly reduced [18F]altanserin binding relative to CW in mesial temporal (amygdala and hippocampus), as well as cingulate cortical regions. In a subset of subjects (11 CW and 16 REC AN), statistical parametric mapping (SPM) confirmed reduced mesial temporal cortex 5HT2A receptor binding and, in addition, showed reduced occipital and parietal cortex binding.. This study extends research suggesting that altered 5-HT neuronal system activity persists after recovery from AN and may be related to disturbances of mesial temporal lobe function. Altered 5-HT neurotransmission after recovery also supports the possibility that this may be a trait-related disturbance that contributes to the pathophysiology of AN.

Topics: Adult; Anorexia Nervosa; Binding, Competitive; Brain; Cerebellum; Convalescence; Female; Fluorodeoxyglucose F18; Humans; Ketanserin; Limbic System; Magnetic Resonance Imaging; Neural Pathways; Radiopharmaceuticals; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Tomography, Emission-Computed