Lower brain-derived neurotrophic factor levels associated with worsening fatigue in prostate cancer patients during repeated stress from radiation therapy

Abstract

Objectives Fatigue during cancer treatment is associated with depression. Neurotrophic factors play a major role in depression and stress and might provide insight into mechanisms of fatigue. This study investigated the association between plasma concentrations of three neurotrophic factors (BDNF, brain-derived neurotrophic factor; GDNF, glial-derived neurotrophic factor; and SNAPIN, soluble N-ethylmaleimide sensitive fusion attachment receptor-associated protein) and initial fatigue intensification during external beam radiation therapy (EBRT) in euthymic non-metastatic prostate cancer men. Methods Fatigue, as measured by the 13-item Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and plasma neurotrophic factors were collected at baseline (prior to EBRT) and mid-EBRT. Subjects were categorized into fatigue and no fatigue groups using a >3-point change in FACT-F scores between the two time points. Multiple linear regressions analysed the associations between fatigue and neurotrophic factors. Results FACT-F scores of 47 subjects decreased from baseline (43.95 ± 1.3) to mid-EBRT (38.36 ± 1.5, P < 0.001), indicating worsening fatigue. SNAPIN levels were associated with fatigue scores (rs = 0.43, P = 0.005) at baseline. A significant decrease of BDNF concentration (P = 0.008) was found in fatigued subjects during EBRT (n = 39). Conclusions Baseline SNAPIN and decreasing BDNF levels may influence worsening fatigue during EBRT. Further investigations are warranted to confirm their role in the pathophysiology and therapeutics of fatigue.

Consortium Building for Nurse Scientists Interested in Symptoms Research in the Era of Precision Health

“…Over the years, nurses have taken the lead to conduct research to understand the complex, multidimensional nature of CRS and to describe symptom biobehavioral underpinnings (Berger, Mitchell, Jacobsen, & Pirl, ; Cantarero‐Villanueva et al, ; Chen, Tsai, Wu, Lin, & Lin, ; Lyon, McCain, Pickler, Munro, & Elswick, ; Miaskowski et al, ; Saligan et al, ; Saligan, Lukkahatai, Holder, Walitt, & Machado‐Vieira, ). Unfortunately, the scientific community has not come to a consensus on a standard definition of symptom phenotypes, which has implications for symptom assessment and management.…”

National Institutes of Health Symptom Science Model sheds light on patient symptoms

“…Another investigation identified that increases in concentrations of two proteins (apolipoprotein E and A1) and a decrease in one (transthyretin) were significantly correlated with clinically significant fatigue intensification during EBRT (Lukkahatai et al, 2014). More recently, the team’s research has revealed that a decline in brain-derived neurotrophic factor levels during EBRT is common among participants who experience high fatigue (Saligan et al, 2015). …”

The Etiology and management of radiotherapy-induced fatigue

“…These biomarkers and biological pathways include alpha-synuclein [34], neurotrophic factors ( BDNF, GDNF , and SNAPIN ) [35], para-inflammatory bystander markers (the interferon alpha-inducible protein 27, IFI27 ) [36], and immunespecific response markers (e.g. MS4A1 ) [37], mitochondrial associated genes ( BCL2L1, FIS2, BCS1L , and SCL25A37 ) as well as RIF-associated biological pathways (glutathione biosynthesis, γ-glutamyl cycle, and antigen presentation pathways) [37].…”

“…Recent efforts are directed at predicting individuals who are at risk to develop RT-related side effects [35,41,83]. One study proposed specific gene signatures to classify and identify individuals who are at risk to develop severe adverse effects from RT [43].…”