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

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

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/m(2). Those in the recAN group were aged 15-29 years and had a mean BMI of 20.5 (SD 1.3) kg/m(2) and the controls were aged 15-26 years and had a BMI of 21.4 (SD 2.1) kg/m(2). 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.

Conclusion: 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.

Figures

Fig. 1
Fig. 1
Mean scores and standard deviations on the Eating Disorders Inventory-2 core subscales and the Symptom Checklist-90-Revised Global Severity Index (T score × 10−1) for long-term weight-recovered patients with anorexia nervosa (recAN group), acutely underweight patients with anorexia nervosa (acAN group) and controls. Significant differences on Tamhane post-hoc tests for multiple comparisons between the acAN and control groups and between the acAN and recAN groups are indicated by asterisks (p < 0.001). There were no statistically significant differences between the recAN and control groups (p = 0.65 for drive for thinness, p = 0.45 for bulimia nervosa, p = 0.23 for body dissatisfaction and p = 0.98 for Global Severity Index).
Fig. 2
Fig. 2
Individual values and group means of serum brain-derived neurotrophic factor in healthy controls, long-term weight-recovered patients with anorexia nervosa and acutely underweight patients with anorexia nervosa. The significant statistical difference between the anorexia groups is indicated by an asterisk (p < 0.005).

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