Serum brain-derived neurotrophic factor and peripheral indicators of the serotonin system in underweight and weight-recovered adolescent girls and women with anorexia nervosa

Serum brain-derived neurotrophic factor and peripheral indicators of the serotonin system in underweight and weight-recovered adolescent girls and women with anorexia nervosa

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J Psychiatry Neurosci 2010; 34(4): 323-329

Stefan Ehrlich, MD; Harriet Salbach-Andrae, PhD; Sarah Eckart; Julia V. Merle; Roland Burghardt, MD; Ernst Pfeiffer, MD; Leonora Franke, PhD; Ralf Uebelhack, MD; Ulrike Lehmkuhl, MD; Rainer Hellweg, MD

Ehrlich, Eckhardt, Franke, Uebelhack, Hellweg — Department of Psychiatry and Psychotherapy; Ehrlich, Salbach-Andrae, Merle, Burghardt, Pfeiffer, Lehmkuhl — Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Charité – Universitätsmedizin Berlin, Berlin, Germany

Abstract

Background: Brain-derived neurotrophic factor (BDNF) mutant mice show hyperphagia and hyperleptinemia. Animal and cell-culture experiments suggest multiple interrelations between BDNF and the serotonin (5-HT) system. We studied serum BDNF in patients with anorexia nervosa and its associations with peripheral indicators of the 5-HT system. To control for secondary effects of acute malnutrition, we assessed acutely underweight patients with anorexia nervosa (acAN) in comparison to long-term weight-recovered patients with the disorder (recAN) and healthy controls.

Methods: We determined serum BDNF, platelet 5-HT content and platelet 5-HT uptake in 33 patients in the acAN group, 20 patients in the recAN group and 33 controls. Plasma leptin served as an indicator of malnutrition.

Results: Patients in the acAN group were aged 14–29 years and had a mean body mass index (BMI) of 14.9 (standard deviation [SD] 1.4) kg/m2. Those in the recAN group were aged 15–29 years and had a mean BMI of 20.5 (SD 1.3) kg/m2 and the controls were aged 15–26 years and had a BMI of 21.4 (SD 2.1) kg/m2. The mean serum BDNF levels were significantly increased in the recAN group compared with the acAN group (8820, SD 3074 v. 6161, SD 2885 pg/mL, U = 154.5, p = 0.001). There were no significant associations between BDNF and either platelet 5-HT content or platelet 5-HT uptake. Among patients with anorexia nervosa, we found significant positive linear relations between BDNF and BMI (r = 0.312, p = 0.023) and between BDNF and leptin (r = 0.365, p = 0.016).

Limitations: We measured the signal proteins under study in peripheral blood.

Conclusions: Serum BDNF levels in patients with anorexia nervosa depend on the state of illness and the degree of hypoleptinemia. Upregulation of BDNF in weight-recovered patients with anorexia nervosa could be part of a regenerative process after biochemical and molecular neuronal injury due to prolonged malnutrition. Associations between the BDNF and the 5-HT system in humans remain to be established.


Submitted Sep. 17, 2008; Revised Feb. 1, 25, 2009; Accepted Feb. 26, 2009

Acknowledgements: The authors would like to thank Mrs. I. Kamenzky for excellent technical assistance and Mrs. D. Weiss for help with the biochemical assessments.

Competing interests: None declared for Ms. Eckart and Merle and Drs. Ehrlich, Salbach-Andrae, Burghardt, Pfeiffer, Franke, Uelbelhack and Lehmkuhl. Dr. Hellweg has travel assistance from Merz Pharmaceutical and Eli Lilly and speaker fees from Merz Pharmaceutical, Pfizer, GlaxoSmithKline, Janssen and Novartis.

Contributors: Drs. Ehrlich, Salbach-Andrae, Pfeiffer, Lehmkuhl and Hellweg designed the study. Ms. Eckart and Merle and Drs. Ehrlich, Burghardt, Franke and Hellweg acquired the data, which Drs. Ehrlich, Salbach-Andrae, Franke, Uebelhack and Hellweg analyzed. Dr. Ehrlich wrote the article, which all other authors reviewed. All authors approved the final version for publication.

Correspondence to: Dr. S. Ehrlich, Harvard Medical School, Department of Psychiatry, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Bldg. 149, 13th Street, Room 2311, Charlestown, MA 02129-2000; fax 617 726-4078; stefan@nmr.mgh.harvard.edu