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      Premorbid body weight predicts weight loss in both anorexia nervosa and atypical anorexia nervosa: Further support for a single underlying disorder

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          Abstract

          Objective

          For adolescents, DSM‐5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI‐centile‐for‐age. We hypothesized that the diagnostic weight cut‐off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN.

          Method

          Based on admission BMI‐centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t‐tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders.

          Results

          Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI‐standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN.

          Discussion

          Whereas the weight cut‐off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight‐specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity.

          Public significance

          Because body weights of patients with AN must drop below the 5th BMI‐centile per DSM‐5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight.

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          Most cited references47

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          Serum immunoreactive-leptin concentrations in normal-weight and obese humans.

          Leptin, the product of the ob gene, is a hormone secreted by adipocytes. Animals with mutations in the ob gene are obese and lose weight when given leptin, but little is known about the physiologic actions of leptin in humans. Using a newly developed radioimmunoassay, wer measured serum concentrations of leptin in 136 normal-weight subjects and 139 obese subjects (body-mass index, > or = 27.3 for men and > or = 27.8 for women; the body-mass index was defined as the weight in kilograms divided by the square of the height in meters). The measurements were repeated in seven obese subjects after weight loss and during maintenance of the lower weight. The ob messenger RNA (mRNA) content of adipocytes was determined in 27 normal-weight and 27 obese subjects. The mean (+/- SD) serum leptin concentrations were 31.3 +/- 24.1 ng per milliliter in the obese subjects and 7.5 +/- 9.3 ng per milliliter in the normal-weight subjects (P < 0.001). There was a strong positive correlation between serum leptin concentrations and the percentage of body fat (r = 0.85, P < 0.001). The ob mRNA content of adipocytes was about twice as high in the obese subjects as in the normal-weight subjects (P < 0.001) and was correlated with the percentage of body fat (r = 0.68, P < 0.001) in the 54 subjects in whom it was measured. In the seven obese subjects studied after weight loss, both serum leptin concentrations and ob mRNA content of adipocytes declined, but these measures increased again during the maintenance of the lower weight. Serum leptin concentrations are correlated with the percentage of body fat, suggesting that most obese persons are insensitive to endogenous leptin production.
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            Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

            Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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              Smoothing reference centile curves: The lms method and penalized likelihood

              Refence centile curves show the distribution of a measurement as it changes according to some covariate, often age. The LMS method summarizes the changing distribution by three curves representing the median, coefficient of variation and skewness, the latter expressed as a Box-Cox power. Using penalized likelihood the three curves can be fitted as cubic splines by non-linear regression, and the extent of smoothing required can be expressed in terms of smoothing parameters or equivalent degrees of freedom. The method is illustrated with data on triceps skinfold in Gambian girls and women, and body weight in U.S.A. girls.
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                Journal
                International Journal of Eating Disorders
                Intl J Eating Disorders
                Wiley
                0276-3478
                1098-108X
                April 2024
                March 25 2024
                April 2024
                : 57
                : 4
                : 967-982
                Affiliations
                [1 ] Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy University Hospital Essen (AöR), University of Duisburg‐Essen Essen Germany
                [2 ] Center for Translational Neuro‐ and Behavioral Sciences, University Hospital Essen, University of Duisburg‐Essen Essen Germany
                [3 ] Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy University Hospital, RWTH Aachen Aachen Germany
                [4 ] Department of Child and Adolescent Psychiatry University Hospital Münster Münster Germany
                [5 ] LWL University Hospital Hamm for Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, Ruhr University‐Bochum Hamm Germany
                [6 ] Department of Child and Adolescent Psychiatry, University Medicine Mainz, Johannes Gutenberg‐University Mainz Germany
                [7 ] kbo‐Heckscher Klinikum for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Academic Teaching Hospital, Ludwig Maximilian University Munich Germany
                [8 ] Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy Faculty of Medicine, Philipps‐University and University Hospital Marburg Marburg Germany
                [9 ] Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus Liebig University Giessen Germany
                [10 ] Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany
                [11 ] Zucker School of Medicine at Hofstra/Northwell, Department of Psychiatry and Molecular Medicine Hempstead New York USA
                [12 ] The Zucker Hillside Hospital, Department of Psychiatry, Northwell Health Glen Oaks New York USA
                [13 ] Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy Centre for Mental Health, University Hospital Würzburg Würzburg Germany
                [14 ] Translational Developmental Neuroscience Section, Division of Psychological and Social Medicine and Developmental Neurosciences Faculty of Medicine TU Dresden Germany
                [15 ] Eating Disorder Research and Treatment Center, Department of Child and Adolescent Psychiatry, Faculty of Medicine TU Dresden Dresden Germany
                [16 ] Department of Child and Adolescent Psychiatry and Psychotherapy University Freiburg Germany
                [17 ] Department of Child and Adolescent Psychiatry Saarland University Homburg Germany
                [18 ] Department of Child &amp; Adolescent Psychiatry and Psychotherapy LVR‐Klinik Viersen Viersen Germany
                [19 ] University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern Bern Switzerland
                [20 ] Clinic of Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg Heidelberg Germany
                [21 ] Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy University of Tübingen Tübingen Germany
                [22 ] Department of Child and Adolescent Psychiatry/Psychotherapy University Hospital Ulm, University of Ulm Germany
                [23 ] Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy LVR Hospital Bonn Bonn Germany
                [24 ] Central Information Office, CIO Marburg GmbH Fronhausen Germany
                [25 ] Department of Psychiatry and Psychology Mayo Clinic Rochester Minnesota USA
                Article
                10.1002/eat.24189
                38528714
                c27f1cd6-1b62-42f0-8b08-9f644081ef6c
                © 2024

                http://creativecommons.org/licenses/by/4.0/

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