The Significance of the FTO Gene for Weight and Body Composition in Swedish Women With Severe Anorexia Nervosa During Intensive Nutrition Therapy.

OBJECTIVE: The aim of this prospective study was to investigate the potential influence of the fat mass and obesity-associated gene (FTO), SNP rs9939609, on body mass index (BMI) and body composition in women with anorexia nervosa (AN) undergoing intensive nutrition therapy. METHOD: Twenty-five female patients with AN (20.1 ± 2.3 years; BMI, 15.5 ± 0.9 kg/m2) were included for 12 weeks of treatment with a high-energy diet. FTO was genotyped and body composition parameters were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography at baseline and after 12 weeks. RESULTS: The distribution of the different FTO genotypes were as follows: AA, 24%; TA, 48%; and TT, 28%. Patients gained a median of 9.8 kg (range, 5.5-17.0 kg) and BMI increased to 19.0 ± 0.9 kg/m2. The increase in BMI, fat mass, and the quotient fat/muscle area was significant for the TT and TA genotype groups. Total lean mass was stable in all genotype groups. We could not demonstrate any difference among the 3 FTO genotypes related to the increases in BMI during nutrition therapy when the additive, dominant, and recessive models of inheritance were applied. CONCLUSIONS: Irrespective of the FTO genotype, there was no difference in weight response during nutrition therapy. Hence, in this small study there was limited support for individualized nutrition therapy for AN based on FTO genotype.

Molecular neuroanatomy of anorexia nervosa.

Anorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using genome-wide methods, recent studies have associated many genes with the disorder. We characterized these genes by projecting them into reference transcriptomic atlases of the prenatal and adult human brain to determine where these genes are expressed in fine detail. We found that genes from an induced stem cell study of anorexia nervosa cases are expressed at higher levels in the lateral parabrachial nucleus. Although weaker, expression enrichment of the adult lateral parabrachial is also found with genes from independent genetic studies. Candidate causal genes from the largest genetic study of anorexia nervosa to date were enriched for expression in the arcuate nucleus of the hypothalamus. We also found an enrichment of anorexia nervosa associated genes in the adult and fetal raphe and ventral tegmental areas. Motivated by enrichment of these feeding circuits, we tested if these genes respond to fasting in mice hypothalami, which highlighted the differential expression of Rps26 and Dalrd3. This work improves our understanding of the neurobiology of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.

Alterations of proteome, mitochondrial dynamic and autophagy in the hypothalamus during activity-based anorexia.

Restrictive anorexia nervosa is associated with reduced eating and severe body weight loss leading to a cachectic state. Hypothalamus plays a major role in the regulation of food intake and energy homeostasis. In the present study, alterations of hypothalamic proteome and particularly of proteins involved in energy and mitochondrial metabolism have been observed in female activity-based anorexia (ABA) mice that exhibited a reduced food intake and a severe weight loss. In the hypothalamus, mitochondrial dynamic was also modified during ABA with an increase of fission without modification of fusion. In addition, increased dynamin-1, and LC3II/LC3I ratio signed an activation of autophagy while protein synthesis was increased. In conclusion, proteomic analysis revealed an adaptive hypothalamic protein response in ABA female mice with both altered mitochondrial response and activated autophagy.

Higher reward value of starvation imagery in anorexia nervosa and association with the Val66Met BDNF polymorphism.

Recent studies support the idea that abnormalities of the reward system contribute to onset and maintenance of anorexia nervosa (AN). Next to cues coding for overweight, other research suggest cues triggering the proposed starvation dependence to be pivotally involved in the AN pathogenesis. We assessed the characteristics of the cognitive, emotional and physiologic response toward disease-specific pictures of female body shapes, in adult AN patients compared with healthy control (HC) women. Frequency and amplitude of skin conductance response (SCR) in 71 patients with AN and 20 HC were registered during processing of stimuli of three weight categories (over-, under- and normal weight). We then assessed the role of the Val66Met BDNF polymorphism as a potential intermediate factor. AN patients reported more positive feelings during processing of underweight stimuli and more negative feelings for normal- and overweight stimuli. The SCR showed a group effect (P=0.007), AN patients showing overall higher frequency of the response. SCR within patients was more frequent during processing of underweight stimuli compared with normal- and overweight stimuli. The Met allele of the BDNF gene was not more frequent in patients compared with controls, but was associated to an increased frequency of SCR (P=0.008) in response to cues for starvation. A higher positive value of starvation, rather than more negative one of overweight, might more accurately define females with AN. The Met allele of the BDNF gene could partly mediate the higher reward value of starvation observed in AN.

High prevalence of vitamin D deficiency and insufficiency in adolescent inpatients diagnosed with eating disorders.

OBJECTIVE: Previous studies assessing vitamin D status in adolescents with eating disorders showed inconsistent results. The aim of the current study was to assess vitamin D status in a large cohort of adolescent inpatients with eating disorders and its relation to bone mineral density (BMD) and depression. METHOD: 25-Hydroxyvitamin D (25OHD), calcium, phosphorus, and alkaline phosphatase levels as well as BMD and depression were assessed on admission in 87 inpatients (aged 16 ± 2 years, females = 81) with eating disorders [anorexia nervosa (AN) = 64; bulimia nervosa (BN) = 5; eating disorders not otherwise specified-binge/purge type (EDNOS-B/P) = 18]. RESULTS: Mean 25OHD levels were 24.1 ± 7.5 ng/ml (25.0 ± 7.6, 25.4 ± 9.9, and 22.0 ± 9.9 ng/ml in patients with AB, BN, and EDNOS-B/P, respectively). Vitamin D deficiency (<15 ng/ml) was found in 7.8% of the patients, and insufficiency (15-20 ng/ml) in 22.2%. Only 16.7% had levels >32 ng/ml, considered optimal by some experts. No associations were found between 25OHD levels and BMD or comorbid depression. 25OHD levels during winter were significantly lower than summer levels (p < .001). Mean lumbar spine BMD z-score in patients with AN and EDNOS-B/P type was low (-1.5 ± 1.1) and correlated with body mass index standard deviation score (p = .03). DISCUSSION: Adolescents with eating disorders show a high prevalence of vitamin D deficiency and insufficiency. Given the risk of osteoporosis in this population, 25OHD levels found in this group may not offer optimal bone protection. Vitamin D levels should be routinely checked and supplementation should be administered as required.

[Pathogenesis of anorexia nervosa. Neurobiological risk factors and possible endophenotypes]. / Az anorexia nervosa kóreredetének újabb megközelítése. Neurobiológiai tényezok és lehetséges endofenotípusok a kutatási eredmények tükrében.

Anorexia nervosa is a serious, chronical state of illness which often starts in childhood or adolescence and has serious consequences on the quality of life. This review focuses on the heterogenity of the disease with emphasis on special diagnostic implications in case of childhood onset. Research findings of the last decade showed that genetic and neurobiological vulnerabilities are at least as potent risk factors as psychological, family constellations and sociocultural preferences. The heritability of eating disorders levels those of diseases predominantly influenced by biological factors. The authors give a summary of the most investigated neurobiologic and neurocognitive factors which could be the fundaments of a biological vulnerablilty. To date, no common risk factor could be identified, but some existing adversities can clearly be related to distinct subgroups with the disorder. The concept of endo- and subphenotypes leads to more specific and more efficient methods of therapy in other somatic and psychiatric diseases.

The genetics of anorexia nervosa.

Anorexia nervosa (AN) is a disease defined by inappropriate weight loss and maintenance of body weight <85% of that expected for weight and height; it is most common in adolescent women aged 15-19 years. Numerous studies have highlighted the familial aggregation of the disease, suggesting a significant genetic component to its etiology. The purpose of this review is to discuss the different fields of genetic research--both in humans and animals--that have contributed to the understanding of this complex disorder. Candidate gene studies focusing on genes involved in the hypothalamic control of appetite and energy regulation have found genetic risk variants that increase risk for AN. A recent genome-wide association study has highlighted novel loci for further investigation in AN. Animal models and epigenetic studies are also considered; the most recent advances in each field and their contributions to the understanding of AN are emphasized.

[Anorexia nervosa--new view on neuroendocrine and genetic determinations]. / Jadlowstret psychiczny--nowe spojrzenie na podloze neuroendokrynne i genetyczne.

Anorexia nervosa is an eating disorder, characterized by low body weight, distorted body image, amenorrhea and an intense fear of gaining weight. The occurrence of anorexia nervosa has increased over the past 10 years among adolescents and young women and it is estimated to occur in 0,5-1% of population. The Anorexia nervosa is not only a psychiatric illness may have many serious gynecological and medical ramifications. Preventive measures to reduce the incidence of anorexia are not known at this time. However, early detection, intervention and cooperation between many specialists can reduce the severity of symptoms and health consequences. Gynecologists assume a broader role in preventative medicine and health maintenance, that is why their awareness of anorexia nervosa is needed. Anorectic patients have metabolic and endocrine complications. Most of them are caused by the dysfunction of hypothalamus, which produces many nueropeptides and neurotransmitters. Anorexia nervosa is characterized by numerous aberrations in neuropeptides and neurotransmitters, such as gonadotropin-releasing hormone, corticotropin-releasing hormone, neuropeptyd Y, leptin, beta-endorfins and serotonine, dopamine. The relationship of anorexia nervosa with genetic factor is being enhanced lower the last few years. However, the studies on the role of polymorphism in some genes brought conflicting results.

[Self-starvation over 1500 years: the work of God, the devil or weight-control?]. / Självsvält under 1,500 år: verk av Gud, djävulen eller viktfixeringen.

For centuries self-starvation among young women has been the subject of intensive discussion. First and foremost it has been a question of debate over aetiological models. During the middle ages, the central issue was whether self-starvation was the work of God or the devil. Subsequently the question was whether the explanation was scientific or religious. The aim of medical science was to find a scientific explanation or debunk the phenomenon as fraudulent. The causes of self-starvation remain unclear. During the nineteenth century, the focus switched back and forth between biological and psychosocial models. Current multifactorial aetiological models take into account biological susceptibility, socio-cultural factors and psychological vulnerability.