Treatment of patients with anorexia nervosa (AN) involves serious difficulties such as "treatment-resistance" during refeeding that need careful consideration of psychopathology of AN from intrinsic/extrinsic risk factors. A lot of literature on AN has revealed that, mixed signaling in the food regulatory system which appears to mirror not only energy intake but also emotions, may underlie characteristic ambivalent eating behaviors in this disorder; however, the key mediator relevant to core psychopathology of AN has not yet to be determined. Further investigations exploring new intrinsic/extrinsic risk factors of pathogenesis of AN are required, and the alarmin system, a homeostatic regulator relevant to nutrition, inflammation, and immune system, is especially noteworthy because of its close association with "treatment-resistance" in AN. We believe that elucidation of pathogenesis of AN from the view of intrinsic/extrinsic risk factors, specifically crosstalk between food regulatory and alarmin systems, is needed to take advantage of possible therapeutic applications in this serious disorder.

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The patients of eating disorders like anorexia nervosa or bulimia nervosa are increasing in number especially among young female. However, the pathology of eating disorders has not been clarified because so many factors as socio-cultural factors, psychological factors, and biological factors are indicated to be concerned. In addition, the methods of treatment have not been established yet. To investigate the biological brain mechanisms of eating disorders, many types of animal models have been proposed. According to the clinical feature of the patients, anorexic status in adolescent female rats was set by food restriction. Psychological and physiological stress changed the feeding behavior in the anorexic status, and the relations of the behavioral changes and the brain neurotransmitters were examined. Those results suggested that abnormalities in many brain neurotransmitters are concerned in anorexic behavior, binge-eating behavior, and anxiety. We can speculate some part of biological bases of human eating disorders, and effective prevention and treatment through such animal models.

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This article describes functional Magnetic Resonance Imaging (fMRI) studies about brain mechanism in eating disorders. We compared the brain activation between men and women during viewing visual stimuli of distorted images of one's own body and processing unpleasant words concerning body image. Women showed significant activation of the bilateral prefrontal cortex and left parahippocampal area including the amygdala upon performing the fat-image. These results suggest that women tend to perceive distorted images of their own bodies by complex cognitive processing of emotion. Women showed amygdala activation while processing unpleasant words concerning body image and perceived these words to be emotionally negative. Furthermore, in the study in eating disorders, significant amygdala activation was shown in AN-R and AN-BP patients but not in BN patients in response to unpleasant body-image words. Significant activation in the medial prefrontal cortex was detected only in AN-BP and BN patients. Our results suggest that activation in the amygdala in response to unpleasant words concerning the body image may be associated with body-image distortion, like extreme weight phobia in AN. Similarly, activation in the medial prefrontal cortex may be associated with abnormal eating behavior, like binge eating/purging. We have identified different brain functions specific to diagnostic subgroups of ED.

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Genetic factors play a significant role in susceptibility to eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). A sib-pair linkage study suggested a linkage region for restricting AN in chromosome 1, 2, 13 and that for BN in chromosome 10. Candidate-gene association studies indicated associations of SLC6A4, HTR2A and BDNF genes with AN in multiple studies. We found that ghrelin gene Leu72Met SNP, -3056T>C SNP, and their haplotype were associated with purging type BN. The same ghrelin gene SNPs were significantly associated with increased body mass index, fat mass, waist circumference, acylated ghrelin concentration and elevated scores in the Drive for Thinness-Body Dissatisfaction in non-clinical young female. In addition, the 3056T>C SNP of the ghrelin gene is related to the probability and rate of change from the restricting type AN to other phenotypes of eating disorders. Our genome-wide association analysis with microsatellite markers identified novel candidate loci for AN at 1q41 and 11q22 in Japanese. A genome-wide association study with SNP markers using recent microarray technique is a promising method in search for susceptibility genes of eating disorders.

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We examined the clinical and psychological features of obsessive anorexia nervosa (AN) patients and discuss the relationship between obsession and perfectionism in AN. Participants were eighty-five AN inpatients who received cognitive behavioral therapy with behavior restriction in our hospital. We classified these AN patients into two groups according to the severity of obsession by use of the Maudsley Obsessional Compulsive Inventory done at admission: A higher obsessive (HO) group who scored 13 points and above and a lower obsessive (LO) group that scored lower than 13 points in the test. The age at onset of AN was lower in the HO group than in the LO group. The percentage of patients with AN subtypes did not differ between the two groups. No difference was found in the rate of drop-out from inpatient treatment and incremental body weight gain during hospital stay between the two groups, suggesting that obsession in AN patients had little influence on the course of inpatient treatment based on cognitive behavioral therapy with behavior restriction. The HO group was associated with the Eating Disorder Inventory subscales "interoceptive awareness", "ineffectiveness" and "perfectionism". Multidimensional Perfectionism Scales revealed that the HO group had higher total scores and higher scores on almost every perfectionism subscale, including self-oriented and socially oriented perfectionism, than the LO group.

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