Increased Brain Histamine H1 Receptor Binding in Patients with Anorexia Nervosa

Background: The central histaminergic neuron system modulates various brain functions, including eating behavior. We hypothesized that women have higher density of histamine H1 receptor (H1R) in the limbic system than men and that the density of central H1R is increased in patients with anorexia nervosa (AN). Methods: Subjects were 12 female AN patients, 12 healthy female subjects, and 11 healthy male subjects. Positron emission tomography with H1R radioligand [¹¹C]doxepin was performed on all subjects and regions of interest based analysis was conducted to evaluate brain H1R binding potential (BP). Abnormal eating behavior, depression, and anxiety of subjects were evaluated using the Eating Attitude Test-26 (EAT-26), Self-Rating Depression Scale (SDS), and State-Trait Anxiety Inventory (STAI), respectively. Results: Binding potential of [¹¹C]doxepin in female subjects was significantly higher than that in male subjects at the following brain sites: amygdala, hippocampus, medial prefrontal cortex, orbitofrontal cortex, and temporal cortex. Anorexia nervosa patients showed significantly higher BP of [¹¹C]doxepin in the amygdala and lentiform nucleus than the control female subjects. In AN patients, BP of [¹¹C]doxepin in the amygdala and thalamus negatively correlated with EAT-26 scores. There was a significant negative correlation between BP of [¹¹C]doxepin and SDS or STAI scores in the amygdala, anterior cingulate cortex, and orbitofrontal cortex of AN patients. Conclusions: These findings support the hypothesis that women have higher H1R density in the limbic system than men and suggest that AN patients may have higher expression of H1R in the limbic brain, particularly in the amygdala.