PiD - Psychotherapie im Dialog 2004; 5(1): 57-62
DOI: 10.1055/s-2003-814807
Aus der Praxis
© Georg Thieme Verlag Stuttgart · New York

Biologie der Anorexia nervosa unter besonderer Berücksichtigung genetischer Aspekte[1]

Johannes  Hebebrand
Further Information

Publication History

Publication Date:
12 March 2004 (online)

Abstract

In dieser Übersichtsarbeit werden aktuelle biologische Erkenntnisse zur Anorexia nervosa zusammengestellt. Die Schwerpunkte liegen bei genetischen Ansätzen und den (neuro-)biologischen Folgen der Semistarvation. Hierbei wird die maßgebliche Bedeutung des Hormons Leptin hervorgehoben.

1 Wir danken den Patientinnen und ihren Familien für die Teilnahme an unseren wissenschaftlichen Studien. Unsere Forschung wird durch DFG, BMBF (Nationales Genomforschungsnetz) und die Europäische Union unterstützt.

Literatur

  • 1 Ahima R S, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier J S. Role of leptin in the neuroendocrine response to fasting.  Nature. 1996;  382 250-252
  • 2 Ballauff A, Ziegler A, Emons G, Sturm G, Blum W F, Remschmidt H, Hebebrand J. Serum leptin and gonadotropin levels in patients with anorexia nervosa during weight gain.  Molecular Psychiatry. 1999;  4 71-75
  • 3 Bergen A W, Bree M B van den, Yeager M, Welch R, Ganjei J K, Haque K, Bacanu S, Berrettini W H, Grice D E, Goldman D, Bulik C M, Klump K, Fichter M, Halmi K, Kaplan A, Strober M, Treasure J, Woodside B, Kaye W H. Candidate genes for anorexia nervosa in the 1p33 - 36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa.  Mol Psychiatry. 2003;  8 397-406
  • 4 Blundell J E, Lawton C L, Halford J C. Serotonin, eating behavior, and fat intake.  Obes Res. 1995;  3, Suppl 4 471-476
  • 5 Brewerton T D, Jimerson D C. Studies of serotonin function in anorexia nervosa.  Psychiatry Res. 1996;  62 31-42
  • 6 Bulik C M, Sullivan P F, Wade T D, Kendler K S. Twin studies of eating disdorders: a review.  Int J Eat Disord. 2000;  27 1-20
  • 7 Bulik C M, Devlin B, Bacanu S A, Thornton L, Klump K L, Fichter M M, Halmi K A, Kaplan A S, Strober M, Woodside D B, Bergen A W, Ganjei J K, Crow S, Mitchell J, Rotondo A, Mauri M, Cassano G, Keel P, Berrettini W H, Kaye W H. Significant linkage an chromosome 10p in families with bulimia nervosa.  Am J Hum Genet. 2003;  72 200-207
  • 8 Coners H, Remschmidt H, Hebebrand J. The relationship between premorbid body weight, weight loss, and weight at referral in adolescent patients with anorexia nervosa.  Int J Eat Disord. 1999;  26 171-178
  • 9 Devlin B, Bacanu S A, Klump K L, Bulik C M, Fichter M M, Halmi K A, Kaplan A S, Strober M, Treasure J, Woodside D B, Berrettini W H, Kaye W H. Linkage analysis of anorexia nervosa incorporating behavioral covariates.  Hum Mol Genet. 2002;  11 689-696
  • 10 Exner C, Hebebrand J, Remschmidt H, Wewetzer C, Ziegler A, Herpertz S, Schweiger U, Blum W F, Preibisch G, Heldmaier G, Klingenspor M. Leptin suppresses semi-starvation induced hyperactivity in rats: Implications for anorexia nervosa.  Molecular Psychiatry. 2000;  5 476-481
  • 11 Frank G K, Kaye W H, Meltzer C C, Price J C, Greer P, McConaha C, Skovira K. Reduced 5-HT2A receptor binding after recovery from anorexia nervosa.  Biol Psychiatry. 2002;  52 896-906
  • 12 Gershon E S, Schreiber J L, Hamovit J R, Dibble E D, Kaye W, Nurnberger J I, Andersen A E, Ebert M. Clinical findings in patients with anorexia nervosa and affective illness in their relatives.  Am J Psychiatry. 1984;  141 1419-1422
  • 13 Gorwood P, Ades J, Bellodi L, Cellini E, Collier D A, Bella D Di, Bernardo M Di, Estivill X, Fernandez-Aranda F, Gratacos M, Hebebrand J, Hinney A, Hu X, Karwautz A, Kipman A, Mouren-Simeoni M C, Nacmias B, Ribases M, Remschmidt H, Ricca V, Rotella C M, Sorbi S, Treasure J. EC Framework V „Factors in Healthy Eating” consortium. The 5-HT(2A) - 1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres.  Mol Psychiatry. 2002;  7 90-94
  • 14 Grice D E, Halmi K A, Fichter M M, Strober M, Woodside D B, Treasure J T, Kaplan A S, Magistretti P J, Goldman D, Bulik C M, Kaye W H, Berrettini W H. Evidence for a susceptibility gene for anorexia nervosa on chromosome 1.  Am J Hum Genet. 2002;  70 787-792
  • 15 Halaas J L, Gajiwala K S, Maffei M, Cohen S L, Chait B T, Rabinowitz D, Lallone R L, Burley S K, Friedman J M. Weight-reducing effects of the plasma protein encoded by the obese gene.  Science. 1995;  269 543-546
  • 16 Hebebrand J, Hinney A. Genetics of eating disorders. In: Medeiros-Neto G, Hlapern A, Bouchard C (eds) Progress in Obesity Research 9. Esher, Surrey, UK; John Libbey Eurotext Limited 2003: 307-312
  • 17 Hebebrand J, Heyden J van der, Devos R, Köpp W, Herpertz S, Remschmidt H, Herzog W. Plasma concentrations of obese protein in anorexia nervosa.  Lancet. 1995b;  346 1624-1625
  • 18 Hebebrand J, Coners H, Barth N, Remschmidt H. Genetik der Essstörungen.  Psycho. 1996a;  22 188-197
  • 19 Hebebrand J, Himmelmann G W, Heseker H, Schäfer H, Remschmidt H. Use of percentiles for the body mass index in anorexia nervosa: Diagnostic, epidemiological, and therapeutic considerations.  International Journal of Eating Disorders. 1996b;  19 359-369
  • 20 Hebebrand J, Himmelmann G W, Wewetzer C, Gutenbrunner C, Heseker H, Schäfer H, Remschmidt H. Body weight in acute anorexia nervosa and at follow-up assessed with percentiles for the body mass index: Implications of a low body weight at referral.  International Journal of Eating Disorders. 1996c;  19 347-357
  • 21 Hebebrand J, Himmelmann G W, Herzog W, Herpertz-Dahlmann B M, Steinhausen H C, Amstein M, Seidel R, Deter H C, Remschmidt H, Schäfer H. Prediction of low body weight at long-term follow-up in acute anorexia nervosa by low body weight at referral.  American Journal of Psychiatry. 1997a;  154 566-569
  • 22 Hebebrand J, Blum W F, Barth N, Coners H, Englaro P, Juul A, Ziegler A, Warnke A, Rascher W, Remschmidt H. Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration.  Mol Psychiatry. 1997b;  2 330-334
  • 23 Hebebrand J, Exner C, Hebebrand K, Holtkamp C, Casper R C, Remschmidt H, Herpertz-Dahlmann B, Klingenspor M. Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia.  Physiol Behav. 2003;  79 25-37
  • 24 Herpertz S, Albers N, Wagner R, Pelz B, Köpp W, Mann K, Blum W F, Senf W, Hebebrand J. Longitudinal changes of circadian leptin, insulin and cortisol plasma levels and their correlation during refeeding in patients with anorexia nervosa.  European Journal of Endocrinology. 2000;  142 373-379
  • 25 Hinney A, Barth N, Ziegler A, Prittwitz S von, Hamann A, Hennighausen K, Lentes K U, Heils A, Rosenkranz K, Roth H, Coners H, Mayer H, Herzog W, Siegfried A, Lehmkuhl G, Poustka F, Schmidt M H, Schäfer H, Grzeschik K H, Pirke K M, Lesch K P, Remschmidt H, Hebebrand J. Serotonin transporter gene-linked polymorphic region: Allele distributions in relationship to body weight and in anorexia nervosa.  Life Sci. 1997;  61 295-303
  • 26 Hinney A, Remschmidt H, Hebebrand J. Candidate gene polymorphisms in eating disorders.  Eur J Pharmacol. 2000;  410 147-159
  • 27 Holland A J, Sicotte N, Treasure J. Anorexia nervosa: evidence for a genetic basis.  J Psychosom Res. 1988;  32 561-571
  • 28 Holtkamp K, Hebebrand J, Mika C, Heer M, Heussen N, Herpertz-Dahlmann B. High serum leptin levels subsequent to weight gain predict renewed weight loss in patients with anorexia nervosa. Neuroendocrinology 2003a (in press)
  • 29 Holtkamp K, Herpertz-Dahlmann B, Mika C, Heer M, Heussen N, Fichter M, Herpertz S, Senf W, Blum W F, Schweiger U, Warnke A, Ballauff A, Remschmidt H, Hebebrand J. Elevated physical activity and low leptin levels co-occur in patients with anorexia nervosa.  Journal of Clinical and Endocrinological Metabolism. 2003b;  88 5169-5174
  • 30 Jimerson D C, Lesem M D, Kaye W H, Brewerton T D. Low serotonin and dopamine metabolite concentrations in cerebrospinal fluid from bulimic patients with frequent binge episodes.  Arch Gen Psychiatry. 1992;  49 132-138
  • 31 Kaye W, Strober M. The neurobiology of eating disorders. In: Charney DS, Nestler EJ, Bunney BS (eds) Neurobiological foundations of mental illness. New York; Oxford University Press 1999: 891-906
  • 32 Kaye W H, Gwirtsman H E, George D T, Ebert M H. Altered serotonin activity in anorexia nervosa after long-term weight restoration. Does elevated cerebrospinal 5-hydroxyindoleacetic acid level correlate with rigid and obsessive behavior?.  Arch Gen Psychiatry. 1991;  48 556-562
  • 33 Kaye W H, Greeno C G, Moss H, Fernstrom J, Fernstrom M, Lilenfeld L R, Weltzin T E, Mann J J. Alterations in serotonin activity and psychiatric symptoms after recovery from bulimia nervosa.  Arch Gen Psychiatry. 1998;  55 (10) 927-935
  • 34 Kaye W H, Lilenfeld L R, Berrettini W H, Strober M, Devlin B, Klump K L, Goldman D, Bulik C M, Halmim K A, Fichter M M, Kaplan A, Woodside D B, Treasure J, Plotnicov K H, Pollice C, Rao R, McConaha C W. A search for susceptibility loci for anorexia nervosa: methods and sample description.  Biol Psychiatry. 2000;  47 794-803
  • 35 Kipman A, Gorwood P, Mouren-Simeoni M C, Ades J. Genetic factors in anorexia nervosa.  Eur Psychiatry. 1999;  14 189-198
  • 36 Lee D W, Leinung M C, Rozhavskaya-Arena M, Grasso P. Leptin and the treatment of obesity: its current status.  Eur J Pharmacol. 2002;  440 129-139
  • 37 Rosenkranz K, Hinney A, Prittwitz S von, Barth N, Ziegler A, Mayer H, Siegfried W, Lehmkuhl G, Poustka F, Schmidt M, Schäfer H, Remschmidt H, Hebebrand J. Screening for mutations in the neuropeptide Y Y5 receptor gene in cohorts belonging to different weight extremes.  International Journal of Obesity. 1998;  22 157-163
  • 38 Steinle N I, Hsueh W C, Snitker S, Pollin T I, Sakul H, St Jean P L, Bell C J, Mitchell B D, Shuldiner A R. Eating behavior in the Old Order Amish: heritability analysis and a genome-wide linkage analysis.  Am J Clin Nutr. 2002;  75 1098-1106
  • 39 Strober M. Family-genetic studies of eating disorders.  J Clin Psychiatry. 1991;  52 9-12
  • 40 Strober M, Freeman R, Lampert C, Diamond J, Kaye W. Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes.  Am J Psychiatry. 2000;  157 393-401
  • 41 Stoving R K, Hangaard J, Hansen-Nord M, Hagen C. A review of endocrine changes in anorexia nervosa.  J Psychiatr Res. 1999;  33 139-152
  • 42 Walters E E, Kendler K S. Anorexia nervosa and anorexic-like syndromes in a population-based female twin sample.  Am J Psychiatry. 1995;  152 64-71
  • 43 Young J K. Estrogen and the etiology of anorexia nervosa.  Neurosci Biohav Rev. 1990;  15 327-331
  • 44 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse obese gene and its human homologue.  Nature. 1994;  372 425-432

1 Wir danken den Patientinnen und ihren Familien für die Teilnahme an unseren wissenschaftlichen Studien. Unsere Forschung wird durch DFG, BMBF (Nationales Genomforschungsnetz) und die Europäische Union unterstützt.

Korrespondenzadresse

Prof. Dr. med. Johannes Hebebrand

Klinische Forschergruppe
Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters

Schützenstraße 49

35039 Marburg

    >