Bulimia nervosa (BN) is a chronic, frequently treatment-resistant disorder, characterized by specific symptoms such as prominent body image distortion, a morbid fear of fatness, binge eating, consequent compensatory behaviors including subsequent self-induced vomiting or laxative abuse, excessive exercising, and self-starvation (American Psychiatric Association, 1994). It remains to be clarified whether characteristic psychological features such as anxiety, depressive symptoms and morbid body image distortion are primary causes or just the result of abnormal eating behaviors.
Brain-derived neurotrophic factor (BDNF) is a member of the family of neurotrophins, which includes nerve growth factor (NGF), neurotrophin-3 (NT-3), NT 4/5, NT-6 and NT-7 (Chaldakov, 2011 and Noble et al., 2011).
BDNF plays an important role in the growth and maintenance of several neuronal systems, serves as a neurotransmitter modulator, and participates in use-dependent plasticity mechanisms, such as learning and memory (Noble et al., 2011). BDNF is widely distributed in the central nervous system, beginning early in development and extending throughout the lifetime. In addition, BDNF and its tyrosine kinase receptor, TrkB, are expressed in various hypothalamic nuclei associated with eating behavior (Kernie et al., 2000). Some authors have demonstrated that hypothalamic BDNF may be an important signaling effector that controls glucose, energy balance and eating behavior (Xu et al., 2003); hence, BDNF, like NGF, is considered not only neurotrophic, but also a metabotrophic factor (Chaldakov, 2011). In the same vein, BDNF knockout mice develop obesity and hyperphagia (Kernie et al., 2000, Rios et al., 2001 and Fox and Byerly, 2004). The infusion of BDNF into the central nervous system induced weight loss, and direct infusion into the hypothalamus decreased feeding (Rios et al., 2001). In addition, in genetically obese, insulin- or leptin-resistant animal models, the peripheral injection of BDNF decreased weight and appetite as well as improved glucose, cholesterol, and nonesterified free fatty acid levels (Tonra et al., 1999, Ono et al., 2000, Nakagawa et al., 2003 and Xu et al., 2003). These results suggest that BDNF is associated with appetite, eating behavior, and conditions linked to cardiometabolic dysfunction, e.g., atherosclerosis, obesity, type 2 diabetes, and metabolic syndrome in humans (Chaldakov et al., 2004).
However, anorexic patients consistently showed lower blood BDNF levels (Nakazato et al., 2003, Monteleone et al., 2004, Monteleone et al., 2005, Nakazato et al., 2009 and Saito et al., 2009). In addition, genetic studies have reported significant and consistent associations of BDNF variants with eating disorder patients (Ribases et al., 2003 and Gratacos et al., 2007). Normal-weight bulimic patients also showed lower blood BDNF (Nakazato et al., 2003 and Monteleone et al., 2005); however, the results were relatively inconsistent compared with anorexic patients. In depressive patients, previous studies consistently reported significantly reduced blood BDNF levels, which were normalized with antidepressant therapy (Shimizu et al., 2003, Huang et al., 2008 and Piccinni et al., 2008). Also, depressive symptoms are common among BN patients (Garfinkel et al., 1980). Thus, the improvement of depressive symptoms could induce the recovery of low BDNF levels even among BN patients.
In the present study, we measured levels of plasma BDNF among BN patients to assess the relationship with psychological symptoms such as depression, anxiety and eating disorder symptoms, employing cross-sectional and longitudinal analyses. We hypothesized that lower plasma BDNF levels would recover to the levels of controls based on the improvement of abnormal eating behaviors as well as psychological symptoms including depression, anxiety, and eating disorder.
