What Amount of Weight Loss Can Entail Anorexia Nervosa or Atypical Anorexia Nervosa After Bariatric Surgery?

Objective: Post-operative development of restrictive eating disorders can occur in patients after bariatric surgery. In children and adolescents with anorexia nervosa (AN) or atypical AN, premorbid body mass index (BMI) has recently been shown to predict total weight loss. We hypothesized that pre-operative BMI similarly predicts weight loss and the development of a restrictive eating disorder in adult bariatric patients.

Unexpected identification of obesity-associated mutations in LEP and MC4R genes in patients with anorexia nervosa.

Mutations leading to a reduced or loss of function in genes of the leptin-melanocortin system confer a risk for monogenic forms of obesity. Yet, gain of function variants in the melanocortin-4-receptor (MC4R) gene predispose to a lower BMI. In individuals with reduced body weight, we thus expected mutations leading to an enhanced function in the respective genes, like leptin (LEP) and MC4R.

Does hypoleptinemia trigger entrapment in anorexia nervosa? Etiological and clinical considerations.

Based on the recent observation that human recombinant leptin (r-Met-hu-leptin; metreleptin) may induce a profound alleviation of the complex symptomatology of patients with anorexia nervosa (AN), we examine the implications for our conceptualisation of this eating disorder. Hypoleptinemia as a core endocrine feature of AN serves as a central and peripheral trigger of tissue-specific adaptations to starvation. In this narrative review, we argue that leptin deficiency may explain many of the puzzling features of this eating disorder.

Case report: Rapid improvements of anorexia nervosa and probable myalgic encephalomyelitis/chronic fatigue syndrome upon metreleptin treatment during two dosing episodes.

A comorbidity of anorexia nervosa (AN) and myalgic encephalomyelitis (ME/CSF) is uncommon. A 17 years-old male adolescent with possible onset of ME/CFS after an Epstein Barr Virus infection (EBV) and later onset of AN during a second period of weight loss was twice treated off-label with metreleptin for 15 and 11 days, respectively. As in previous cases, eating disorder specific cognitions and mood improved.

Case report: clinical improvements observed in first off-label metreleptin treatment of a patient with atypical anorexia nervosa.

Off-label metreleptin treatment resulted in cognitive, emotional and behavioral improvements of patients with anorexia nervosa, who presented with hypoleptinemia. We now report a case study of a 16-year-old female patient with atypical anorexia nervosa who was treated off-label with metreleptin for 11 days. She had lost 21 kg over 6 months.

The role of leptin in rodent and human sleep: A transdiagnostic approach with a particular focus on anorexia nervosa.

This narrative review addressed to both clinicians and researchers aims to assess the role of hypoleptinemia in disordered sleep with a particular focus on patients with anorexia nervosa (AN). After introducing circadian rhythms and the regulation of circulating leptin, we summarize the literature on disordered sleep in patients with AN and in fasting subjects in general. We highlight novel single-case reports of substantially improved sleep within days after initiation of off-label metreleptin treatment.

Rapid Emergence of Appetite and Hunger Resulting in Weight Gain and Improvement of Eating Disorder Symptomatology during and after Short-Term Off-Label Metreleptin Treatment of a Patient with Anorexia Nervosa.

Off-label treatment of a 15-year-old female patient with anorexia nervosa (AN) with human recombinant leptin (metreleptin) for nine days was associated with self-reported increments of appetite and hunger resulting in rapid weight gain and substantial improvement of eating disorder cognitions and of depression. The results further substantiate the effects of metreleptin on both AN and depression. We contrast these results with the widespread view that leptin is an anorexigenic hormone.

Suggestive Evidence for an Antidepressant Effect of Metreleptin Treatment in Patients with Lipodystrophy.

Introduction: Lipodystrophy (LD) syndromes are rare heterogeneous disorders characterized by reduction or absence of subcutaneous fat, low or nondetectable leptin concentrations in blood and impaired hunger/satiety regulation. Metreleptin treatment reverses metabolic complications and improves eating behavior in LD. Because depression in anorexia nervosa (AN), which is also characterized by hypoleptinemia, improves substantially upon treatment with metreleptin, we hypothesized that metreleptin substitution may be associated with an antidepressant effect in patients with LD, too.

First Account of Psychological Changes Perceived by a Female with Congenital Leptin Deficiency upon Treatment with Metreleptin.

Two psychiatric interviews of a 39-year old female with congenital leptin deficiency were conducted to define psychological changes 14 and 165 days after initiation of treatment with human recombinant leptin (metreleptin). The most pronounced initial experience related to the reduced preoccupation with food. An improved mood was reported by the patient, which she associated with this reduced preoccupation.

The role of hypoleptinemia in the psychological and behavioral adaptation to starvation: Implications for anorexia nervosa.

This narrative review aims to pinpoint mental and behavioral effects of starvation, which may be triggered by hypoleptinemia and as such may be amenable to treatment with leptin receptor agonists. The reduced leptin secretion results from the continuous loss of fat mass, thus initiating a graded triggering of diverse starvation related adaptive functions. In light of leptin receptors located in several peripheral tissues and many brain regions adaptations may extend beyond those of the hypothalamus-pituitary-end organ-axes.

PTBP2 - a gene with relevance for both Anorexia nervosa and body weight regulation.

Genetic factors are relevant for both eating disorders and body weight regulation. A recent genome-wide association study (GWAS) for anorexia nervosa (AN) detected eight genome-wide significant chromosomal loci. One of these loci, rs10747478, was also genome-wide and significantly associated with body mass index (BMI).

Suggestive Evidence for Causal Effect of Leptin Levels on Risk for Anorexia Nervosa: Results of a Mendelian Randomization Study.

Genetic correlations suggest a coexisting genetic predisposition to both low leptin levels and risk for anorexia nervosa (AN). To investigate the causality and direction of these associations, we performed bidirectional two-sample Mendelian randomization (MR) analyses using data of the most recent genome-wide association study (GWAS) for AN and both a GWAS and an exome-wide-association-study (EWAS) for leptin levels. Most MR methods with genetic instruments from GWAS showed a causal effect of lower leptin levels on higher risk of AN (e.

[Genetic Analyses of Complex Phenotypes Through the Example of Anorexia Nervosa and Bodyweight Regulation].

Genetic Analyses of Complex Phenotypes Through the Example of Anorexia Nervosa and Bodyweight Regulation Genetics variants are important for the regulation of bodyweight and also contribute to the genetic architecture of eating disorders. For many decades, family studies, a subentity of so-called formal genetic studies, were employed to determine the genetic share of bodyweight and eating disorders and found heritability rates exceeding 50 % with both phenotypes. Because of this significant contribution of genetics, the search for those genes and their variants related to the variance in bodyweight and the etiology of eating disorders - or both - was commenced by the early 1990s.

Lack of Evidence for a Relationship Between the Hypothalamus-Pituitary-Adrenal and the Hypothalamus-Pituitary-Thyroid Axis in Adolescent Depression.

In adults with major depressive disorder (MDD), a dysfunction between the hypothalamus-pituitary-adrenal (HPA) and the hypothalamus-pituitary-thyroid (HPT) axis has been shown, but the interaction of both axes has not yet been studied in adolescent major depressive disorder (MDD). Data from 273 adolescents diagnosed with MDD from two single center cross-sectional studies were used for analysis. Serum levels of thyrotropin (TSH), free levothyroxine (fT4), and cortisol were determined as indicators of basal HPT and HPA axis functioning and compared to that of adolescent controls by t-tests.

Increased Prevalence of Subclinical Hypothyroidism and Thyroid Autoimmunity in Depressed Adolescents: Results From a Clinical Cross-Sectional Study in Comparison to the General Pediatric Population.

Objective: The study was undertaken to determine the prevalence of subclinical and overt thyroid dysfunction as well as thyroid autoimmunity in depressed adolescents in comparison to the general pediatric population. Additionally, the relationship between parameters of thyroid function and Beck Depression Inventory-II (BDI-II) scores was examined.

Methods: Parameters of thyroid function (thyrotropin, free thyroxine, thyroid peroxidase antibodies) and prevalence of thyroid dysfunction and autoimmunity were determined in 360 adolescents (11-19 years) with at least mild depression (BDI-II score > 13) between June 2016 and December 2019 and in a representative reference cohort without evidence of impaired mental health from a nationwide survey (German Health Interview and Examination Survey for Children and Adolescents [KiGGS], 2003-2006).

Rapid amelioration of anorexia nervosa in a male adolescent during metreleptin treatment including recovery from hypogonadotropic hypogonadism.

With this case report we support our medical hypothesis that metreleptin treatment ameliorates starvation related emotional, cognitive and behavioral symptomatology of anorexia nervosa (AN) and show for the first time strong effects in a male patient with AN. A 15.9 year old adolescent with severe AN of eight-month duration was treated off-label with metreleptin.

Evaluation of Metabolic Profiles of Patients with Anorexia Nervosa at Inpatient Admission, Short- and Long-Term Weight Regain-Descriptive and Pattern Analysis.

Acute anorexia nervosa (AN) constitutes an extreme physiological state. We aimed to detect state related metabolic alterations during inpatient admission and upon short- and long-term weight regain. In addition, we tested the hypothesis that metabolite concentrations adapt to those of healthy controls (HC) after long-term weight regain.

A mendelian randomization study on causal effects of 25(OH)vitamin D levels on attention deficit/hyperactivity disorder.

Background: While observational studies revealed an inverse association between serum 25(OH)vitamin D (25(OH)D) and the risk of attention deficit/hyperactivity disorder (ADHD), the causality of this relationship remains unclear.

Methods: We conducted a bidirectional two-sample Mendelian Randomization (MR) study to examine whether 25(OH)D has an effect on the risk to develop ADHD or vice versa. Information on single nucleotide polymorphisms (SNP) associated with serum 25(OH)D was obtained from a genome-wide association study (GWAS) considering phenotype data from 79,366 individuals of European ancestry.

Short-term metreleptin treatment of patients with anorexia nervosa: rapid on-set of beneficial cognitive, emotional, and behavioral effects.

To examine the hypothesis that normalization of low circulating leptin levels in patients with anorexia nervosa ameliorates hyperactivity, three seriously ill females with hyperactivity were treated off-label with metreleptin (recombinant human leptin) for up to 14 days. Drive for activity, repetitive thoughts of food, inner restlessness, and weight phobia decreased in two patients. Surprisingly, depression improved rapidly in all patients.

The Role of Genetic Variation of BMI, Body Composition, and Fat Distribution for Mental Traits and Disorders: A Look-Up and Mendelian Randomization Study.

Anthropometric traits and mental disorders or traits are known to be associated clinically and to show genetic overlap. We aimed to identify genetic variants with relevance for mental disorders/traits and either (i) body mass index (or obesity), (ii) body composition, (and/or) (iii) body fat distribution. We performed a look-up analysis of 1,005 genome-wide significant SNPs for BMI, body composition, and body fat distribution in 15 mental disorders/traits.

Effect of vitamin D deficiency on depressive symptoms in child and adolescent psychiatric patients: results of a randomized controlled trial.

Purpose: While observational studies revealed inverse associations between serum vitamin D levels [25(OH)D] and depression, randomized controlled trials (RCT) in children and adolescents are lacking. This RCT examined the effect of an untreated vitamin D deficiency compared to an immediate vitamin D supplementation on depression scores in children and adolescents during standard day and in-patient psychiatric treatment.

Methods: Patients with vitamin D deficiency [25(OH)D ≤ 30 nmol/l] and at least mild depression [Beck Depression Inventory II (BDI-II) > 13] (n = 113) were 1:1 randomized into verum (VG; 2640 IU vitamin D/d) or placebo group (PG) in a double-blind manner.

Assessing causal links between metabolic traits, inflammation and schizophrenia: a univariable and multivariable, bidirectional Mendelian-randomization study.

Background: Blood immunoreactive biomarkers, such as C-reactive protein (CRP), and metabolic abnormalities have been associated with schizophrenia. Studies comprehensively and bidirectionally probing possible causal links between such blood constituents and liability to schizophrenia are lacking.

Methods: To disentangle putative causal links between CRP blood levels and schizophrenia in both directions, we conducted multiple univariable Mendelian-randomization (MR) analyses, ranging from fixed-effect to inverse variance-weighted (IVW), weighted-median, MR Egger and generalized summary-data-based Mendelian-randomization (GSMR) models.