B. Estour

Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: Association with subtype, body-mass index, severity and age of onset.

Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade and is strongly familial with genetic factors. Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptins effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight. Obestatin which counteracts ghrelin action on feeding is derived from the same propeptide than ghrelin. BDNF has been involved in body weight regulation and its Val66Met polymorphism associated with AN. We therefore re-investigated the association between AN and the Leu72Met and Gln90Leu polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes (restrictive--ANR--and bingeing/purging--ANB--subtypes). Family trios study of these 4 single nucleotide polymorphisms were performed in 114 probands with AN and both their parents recruited in two specialized French centres. A transmission disequilibrium was observed for the Leu72Met SNP of the preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by clinical subtype, these two polymorphisms were preferentially transmitted for the trios with a bingeing/purging proband. An excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed. These results do not provide evidence for a preferential transmission of the 66Met allele of BDNF but support the hypothesis that ghrelin and AGRP polymorphisms confers susceptibility to AN. Further simultaneous analysis of genetic variants of the biological determinants of energy metabolism and feeding behaviour in very large populations should contribute to the understanding of the high degree of heritability of eating disorders and to the description of pathophysiological patterns leading to life-threatening conditions in a highly redundant system.

Alteration of the QT rate dependence in anorexia nervosa

Myocardial repolarization has been evaluated in patients with anorexia nervosa (AN) with conflicting results. The authors postulated that dynamic alterations in QT interval adaptation could characterize these patients. This study compared QT dynamicity along RR intervals from 24‐hour ECG data of patients with and without AN. Twenty‐five patients (23 women) fulfilling the Diagnostic and Statistical Manual (DSM IV) criteria for AN were included in the study. All underwent 24‐hour ECG Holter recordings, allowing QT and RR measurements, and heart rate variability (HRV) analysis in free‐living conditions. A group of 25 sex‐ and age‐matched healthy subjects served as controls. Compared with controls, AN patients presented with relative bradycardia, more particularly during night periods but neither mean QT nor corrected mean QT length (calculated using Bazett formula) over the 24 hours of monitoring differed. However, QT/RR slope was found significantly enhanced compared with normals (− 2.00 ± 0.53 vs − 1.42 ± 0.40) (P = 0.006): QT length related to heart rate was found longer for a heart rate <55 beats/min in AN. Mean 24‐hours QT length appears unaltered in AN in the absence of electrolytic disorders. However, the QT/RR relationship was enhanced reflecting the specific autonomic imbalance encountered in this population. The clinical implications of such findings need to be discussed since an equivalent enhancement of QT/RR slope has been described after myocardial infarction in patients presenting life‐threatening ventricular arrhythmias.

Chronotropic incompetence to exercise separates low body weight from established anorexia nervosa.

Chronotropic incompetence (CI), characterized by an attenuated heart rate (HR) response to exercise could participate to the limitation of exercise capacity in anorexia nervosa (AN). Therefore, we evaluated the role of cardiac sympathetic responsiveness in AN patients. In addition, the ambulatory value of autonomic control using spectral analysis of heart rate variability (HRV) was determined and correlated to maximal exercise performance. Twenty‐two patients hospitalized for weight loss and suspicion of AN were included in the study. All performed a symptom‐limited exercise test with measurement of gas exchange for chronotropic response to exercise evaluation. Holter ECG recordings allowed daytime and night‐time spectral domain HRV analysis in order to evaluate the alteration of sympathetic control of HR in free‐living conditions. CI defined as a failure to achieve 80% of heart rate reserve (%HRR) was observed in 13 (59%) patients (CI+). This group presented a higher body mass deficit than the group without CI (CI−; −35·1 ± 8·7% versus −26·1 ± 10·7%; P<0·05). Obviously, patients with a lower body mass index (BMI < 16 kg m−2, n = 14) revealed a more severe limitation to maximal exercise with a lower peak HR, a lower peak Vo2, and a lower maximal O2 pulse (P<0·05). BMI was significantly correlated to peak Vo2, maximal HR, and %HRR achieved at peak exercise. Daytime HRV parameters reflecting the sympathetic autonomic equilibrium (LF nu, LF/HF ratio) were significantly lower in CI+ patients. Blunted sympathetic response to maximal exercise is frequent and correlated to weight deficit. The present data suggest a major autonomic derangement in AN characterized by a cardiac sympathetic withdrawal.

Differentiating constitutional thinness from anorexia nervosa in DSM 5 era

INTRODUCTION Constitutional thinness (CT) is an underweight state characterized by normal menstruations and no change in feeding behaviour. Thinness is the only resemblance between Anorexia Nervosa (AN) and CT. Removal of amenorrhea from the new DSM 5 definition of AN might result in misdiagnosis between these two populations. The objective of this study was to compare CT, AN and Control subjects in terms of biological, anthropometric, and psychological markers in order to better distinguish AN from CT subjects. MATERIALS AND METHODS Body composition, nutritional markers, pituitary hormones, bone markers and psychological scores were evaluated in three groups of young women: fifty-six CT, forty restrictive-type AN and fifty-four Control subjects. For every marker, a receiver Operator Characteristics (ROC) curve was calculated to evaluate the accuracy of differentiation between AN and CT groups. RESULTS For most studied parameters, CT subjects were similar to Controls but dramatically different from AN subjects. DEBQ Restrained Eating subscale score was identified by ROC data analysis as the only psychological parameter tested to successfully differentiate AN from CT. Free-T3 and Leptin were shown to be powerful markers to differentiate AN and CT populations as they were highly specific and sensitive ones. CONCLUSION The exclusive use of psychological testing criteria is not always sufficient to differentiate AN and CT patients. Minimally, additional testing of Free T3 levels, which is cheap and widely accessible for general practitioners, should be completed to avoid misdiagnosis which could result in the implementation of ineffective treatment plans and social stigmatization for CT women.