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.
Key words
Starvation - Leptin - Fertilität - Hyperaktivität - Genomscan - Kandidatengenansatz
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
