Objectives: Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays an important role in weight regulation and eating behaviors as well as in the activity-dependent neuroplasticity underlying learning and memory behaviors involving the hippocampus. In anorexia nervosa (AN) patients, abnormal serum BDNF concentrations, cognitive impairments and specific personality traits have been traditionally observed. This study explores the levels of four serum neurotrophins [BDNF, neurotrophin 3 (NTF3), neurotrophin 4 (NTF4) and glial cell line-derived neurotrophic factor (GDNF)] with respect to their use as potential biomarkers for AN. This study also investigates any associations that might exist between serum neurotrophin levels and neurocognitive impairment or personality traits. Methods: Serum neurotrophin concentrations were measured in 60 AN patients (AN group) and 45 healthy controls (HC group). We correlated the serum levels of the four neurotrophins BDNF, NTF3, NTF4 and GDNF and the clinical type of anorexia. We also analyzed the relationship between serum neurotrophin levels and the Beck Depression Inventory, body mass index, executive functions by the Wisconsin Card Sorting test (WCST) and personality dimensions by the Temperament and Character Inventory (TCI) test. Results: Serum NTF4 concentrations were significantly lower when comparing all AN patients (34.7 ± 72.5 pg/ml) or restriction type AN patients (29.1 ± 62.5 pg/ml) with the HC group (58.4 ± 135.8 pg/ml; p = 0.004 and p = 0.005, respectively). A significant correlation (p < 0.005) between BDNF serum levels and patient personality dimensions as measured by the TCI test was observed. Furthermore, significant correlations were observed between NTF4 and GDNF serum levels and executive function as measured by the WCST. Conclusions: These data suggest that NTF4 might serve as a biomarker for AN. Furthermore, BDNF and GDNF serum levels appear to be associated with personality traits and executive function.

Keywords:
Neurotrophin 3, Neurotrophin 4, Wisconsin Card Sorting test, Temperament and Character Inventory test, Anorexia nervosa, Brain-derived neurotrophic factor, Glial cell line-derived neurotrophic factor
1.
Connan F, Campbell IC, Katzman M, Lightman SL, Treasure J: A neurodevelopmental model for anorexia nervosa. Physiol Behav 2003;79:13–24.
2.
Kernie SG, Liebl DJ, Parada LF: BDNF regulates eating behavior and locomotor activity in mice. EMBO J 2000;19:1290–1300.
3.
Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, Reichardt LF: Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 2003;6:736–742.
4.
King BM: The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav 2006;87:221–244.
5.
Lebrun B, Bariohay B, Moyse E, Jean A: Brain-derived neurotrophic factor (BDNF) and food intake regulation: a minireview. Auton Neurosci 2006;126–127:30–38.
6.
Lee J, Seroogy KB, Mattson MP: Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. J Neurochem 2002;80:539–547.
7.
Mercader JM, Saus E, Aguera Z, Bayes M, Boni C, Carreras A, Cellini E, de Cid R, Dierssen M, Escaramis G, Fernandez-Aranda F, Forcano L, Gallego X, Gonzalez JR, Gorwood P, Hebebrand J, Hinney A, Nacmias B, Puig A, Ribases M, Ricca V, Romo L, Sorbi S, Versini A, Gratacos M, Estivill X: Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders. Hum Mol Genet 2008;17:1234–1244.
8.
Rybakowski F, Dmitrzak-Weglarz M, Szczepankiewicz A, Skibinska M, Slopien A, Rajewski A, Hauser J: Brain-derived neurotrophic factor gene Val66Met and -270C/T polymorphisms and personality traits predisposing to anorexia nervosa. Neuro Endocrinol Lett 2007;28:153–158.
9.
Nakazato M, Tchanturia K, Schmidt U, Campbell IC, Treasure J, Collier DA, Hashimoto K, Iyo M: Brain-derived neurotrophic factor (BDNF) and set-shifting in currently ill and recovered anorexia nervosa (AN) patients. Psychol Med 2009;39:1029–1035.
10.
Brandys MK, Kas MJ, van Elburg AA, Campbell IC, Adan RA: A meta-analysis of circulating BDNF concentrations in anorexia nervosa. World J Biol Psychiatry 2011;12:444–454.
11.
McLennan SN, Mathias JL: The depression-executive dysfunction (DED) syndrome and response to antidepressants: a meta-analytic review. Int J Geriatr Psychiatry 2010;25:933–944.
12.
Champely S: Basic functions for power analysis. R package version 1.1.1. http://CRANR-projectorg/package=pwr 2009.
13.
Kowalska I, Karczewska-Kupczewska M, Straczkowski M: Adipocytokines, gut hormones and growth factors in anorexia nervosa. Clin Chim Acta 2011;412:1702–1711.
14.
Koizumi H, Hashimoto K, Itoh K, Nakazato M, Shimizu E, Ohgake S, Koike K, Okamura N, Matsushita S, Suzuki K, Murayama M, Higuchi S, Iyo M: Association between the brain-derived neurotrophic factor 196G/A polymorphism and eating disorders. Am J Med Genet B Neuropsychiatr Genet 2004;127B:125–127.
15.
Ribases M, Gratacos M, Fernandez-Aranda F, Bellodi L, Boni C, Anderluh M, Cristina Cavallini M, Cellini E, Di Bella D, Erzegovesi S, Foulon C, Gabrovsek M, Gorwood P, Hebebrand J, Hinney A, Holliday J, Hu X, Karwautz A, Kipman A, Komel R, Nacmias B, Remschmidt H, Ricca V, Sorbi S, Tomori M, Wagner G, Treasure J, Collier DA, Estivill X: Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations. Eur J Hum Genet 2005;13:428–434.
16.
Dmitrzak-Weglarz M, Skibinska M, Slopien A, Szczepankiewicz A, Rybakowski F, Kramer L, Hauser J, Rajewski A: BDNF Met66 allele is associated with anorexia nervosa in the Polish population. Psychiatr Genet 2007;17:245–246.
17.
Nakazato M, Hashimoto K, Yoshimura K, Hashimoto T, Shimizu E, Iyo M: No change between the serum brain-derived neurotrophic factor in female patients with anorexia nervosa before and after partial weight recovery. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:1117–1121.
18.
Monteleone P, Fabrazzo M, Martiadis V, Serritella C, Pannuto M, Maj M: Circulating brain-derived neurotrophic factor is decreased in women with anorexia and bulimia nervosa but not in women with binge-eating disorder: relationships to co-morbid depression, psychopathology and hormonal variables. Psychol Med 2005;35:897–905.
19.
Ehrlich S, Salbach-Andrae H, Eckart S, Merle JV, Burghardt R, Pfeiffer E, Franke L, Uebelhack R, Lehmkuhl U, Hellweg R: Serum brain-derived neurotrophic factor and peripheral indicators of the serotonin system in underweight and weight-recovered adolescent girls and women with anorexia nervosa. J Psychiatry Neurosci 2009;34:323–329.
20.
Lang UE, Hellweg R, Gallinat J: BDNF serum concentrations in healthy volunteers are associated with depression-related personality traits. Neuropsychopharmacology 2004;29:795–798.
21.
Terracciano A, Martin B, Ansari D, Tanaka T, Ferrucci L, Maudsley S, Mattson MP, Costa PT Jr: Plasma BDNF concentration, Val66Met genetic variant and depression- related personality traits. Genes Brain Behav 2010;9:512–518.
22.
Jakubczyk A, Zechowski C, Namysłowska I: Anorexia nervosa – different characters, different therapies; in: Treatment of Anorexia and Bulimia Nervosa: What, When, to Whom. Krakow, Polish Psychiatric Association, 2003.
23.
Bulik CM, Thornton L, Pinheiro AP, Plotnicov K, Klump KL, Brandt H, Crawford S, Fichter MM, Halmi KA, Johnson C, Kaplan AS, Mitchell J, Nutzinger D, Strober M, Treasure J, Woodside DB, Berrettini WH, Kaye WH: Suicide attempts in anorexia nervosa. Psychosom Med 2008;70:378–383.
24.
Amianto F, Abbate-Daga G, Morando S, Sobrero C, Fassino S: Personality development characteristics of women with anorexia nervosa, their healthy siblings and healthy controls: what prevents and what relates to psychopathology? Psychiatry Res 2011;187:401–408.
25.
Nicole O, Ali C, Docagne F, Plawinski L, MacKenzie ET, Vivien D, Buisson A: Neuroprotection mediated by glial cell line-derived neurotrophic factor: involvement of a reduction of NMDA-induced calcium influx by the mitogen-activated protein kinase pathway. J Neurosci 2001;21:3024–3033.
26.
Diniz BS, Teixeira AL, Miranda AS, Talib LL, Gattaz WF, Forlenza OV: Circulating glial-derived neurotrophic factor is reduced in late-life depression. J Psychiatr Res 2012;46:135–139.
27.
Fernandes BS, Gama CS, Walz JC, Cereser KM, Fries GR, Colpo G, Aguiar B, Pfaffenseller B, Kauer-Sant’anna M, Kapczinski F: Increased neurotrophin-3 in drug-free subjects with bipolar disorder during manic and depressive episodes. J Psychiatr Res 2010;44:561–565.
28.
Walz JC, Magalhaes PV, Giglio LM, Cunha AB, Stertz L, Fries GR, Andreazza AC, Kapczinski F: Increased serum neurotrophin-4/5 levels in bipolar disorder. J Psychiatr Res 2009;43:721–723.
29.
Heberlein A, Muschler M, Wilhelm J, Frieling H, Lenz B, Groschl M, Kornhuber J, Bleich S, Hillemacher T: BDNF and GDNF serum levels in alcohol-dependent patients during withdrawal. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:1060–1064.
30.
Trajkovska V, Marcussen AB, Vinberg M, Hartvig P, Aznar S, Knudsen GM: Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data. Brain Res Bull 2007;73:143–149.
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2012
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