The Role of Central and Peripheral Brain-Derived Neurotrophic Factor (BDNF) as a Biomarker of Anorexia Nervosa Reconceptualized as a Metabo-Psychiatric Disorder

Abstract

Neurotrophic factors play pivotal roles in shaping brain development and function, with brain-derived neurotrophic factor (BDNF) emerging as a key regulator in various physiological processes. This review explores the intricate relationship between BDNF and anorexia nervosa (AN), a complex psychiatric disorder characterized by disordered eating behaviors and severe medical consequences. Beginning with an overview of BDNF's fundamental functions in neurodevelopment and synaptic plasticity, the review delves into recent clinical and preclinical evidence implicating BDNF in the pathophysiology of AN. Specifically, it examines the impact of BDNF polymorphisms, such as the Val66Met variant, on AN susceptibility, prognosis, and treatment response. Furthermore, the review discusses the interplay between BDNF and stress-related mood disorders, shedding light on the mechanisms underlying AN vulnerability to stress events. Additionally, it explores the involvement of BDNF in metabolic regulation, highlighting its potential implications for understanding the metabolic disturbances observed in AN. Through a comprehensive analysis of clinical data and animal studies, the review elucidates the nuanced role of BDNF in AN etiology and prognosis, emphasizing its potential as a diagnostic and prognostic biomarker. Finally, the review discusses limitations and future directions in BDNF research, underscoring the need for further investigations to elucidate the complex interplay between BDNF signaling and AN pathology.

Keywords: anorexia nervosa; brain-derived neurotrophic factor (BDNF); eating disorders; metabolism; val66met polymorphism.

Figure 4

Brain circuits implicated in anorexia symptomatology. PFC: prefrontal cortex. DS: dorsal striatum. NAc: nucleus accumbens. AMY: amygdala. HIP: hippocampus. VTA: ventral tegmental area. HPT: hypothalamus [96,97,98].

Figure 1

Multifaceted symptoms of anorexia nervosa.

Figure 2

Signaling Pathways of BDNF Protein. This figure illustrates the primary signaling pathways activated by BDNF binding to its receptors, TrkB and p75NTR. Upon mBDNF binding, TrkB receptors initiate downstream signaling cascades and promote neuronal survival, synaptic plasticity, synaptogenesis, and long-term potentiation (LTP). The interaction of pro-BDNF with its receptor p75NTR is involved in apoptosis, pruning and retraction of synaptogenesis, and long-term depression (LTD).

Figure 3

Influence of Val66Met polymorphism on molecular mechanisms and physiological outcomes related with AN. The molecular level effects of the Val66Met polymorphism include alterations in BDNF signaling towards p57 receptor, and a decrease in the availability of mBDNF. At the physiological level, human Met carriers are more likely to develop psychiatric vulnerabilities to environmental stress and metabolic diseases such as obesity. Certain influences of the Val66Met polymorphism exhibit sexual dimorphism. In the context of AN, Met alleles are currently of interest.