Does lower brain-derived neurotrophic factor in adolescent waterpipe smokers suggest a negative effect on the developing brain?

Abstract

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that are pivotal for neuronal function; it supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. BDNF is active in the hippocampus, cortex, and basal forebrain. It has been implicated in learning and higher cognitive function and is associated with intelligence and attention (Bathina and Undurti, 2015). Lower serum levels of BDNF correlate with cardiovascular risk factors and a wide variety of psychiatric and neurodegenerative diseases (Kaess et al., 2015), particularly in adolescents (Pedersen et al., 2017) Studies of the effects of cigarette smoking on BDNF in adults have reported mixed results. The recent publication by Alomari et al. “Brainderived neutrophic factor in adolescents smoking waterpipe: The Irbid TRY” is the first study to evaluate the effect of waterpipe (WP) smoking on serum levels of BDNF among adolescents (mean (SD) age 14.4 (1.1)) (Alomari et al., 2018). The Irbid TRY was conducted in Jordan. The comparison of serum BDNF levels between WP users and non-users may provide insight on the health effects of WP smoking on the developing brains of adolescents. The data utilized by Alomari et al., are part of the “Irbid Tobacco Risk in Youth (Irbid-TRY)” longitudinal project (Alomari and Al-Sheyab, 2017). In the sub-study, blood samples were obtained from 483 adolescents enrolled in the descriptive, cross-sectional study. Serum BDNF levels were strongly correlated with WP smoking, sex, BMI and location (rural vs. urban) but not age, with lower BDNF found in males and in WP smokers. While lower levels of BDNF in males have been reported previously (Begliuomini et al., 2007), the lower BDNF level among adolescents smoking WP is a novel finding. The study results suggest that WP smoking may decrease BDNF levels and predispose adolescents to adverse health effects, including effects on cognitive function. Nevertheless, the interpretation of the results is limited due to several shortcomings. First and foremost, cognitive assessments were not performed so the cognitive effects of WP smoking associated with changes in BDNF were not assessed. Only one blood sample was obtained per person; thus, temporal changes and associations cannot be evaluated. Further, it is unknown how the circadian rhythm of BDNF secretion in adolescents is affected by WP smoking (Begliuomini et al., 2008; Cain et al., 2017). Moreover, blood samples were obtained in the morning, and may not reflect recent WP use. While the study sample size was substantial, there was no control for amount and frequency of WP use, tobacco type and flavor, or topography. Health effects noted by the participants were evaluated based on self-report. While it is known that food intake (and/or diet) and level of physical activity (Whiteman et al., 2014) may impact serum BDNF levels, there was no control for these factors in the study. The BDNF Val66Met polymorphism has been reported to be associated with cognitive dysfunctions and other brain disorders; however, the study did not assess if the participants were Met-allele carriers in comparison to Val homozygotes (Hennings et al., 2019; Harrisberger et al., 2015). WP smoking is increasing among youth worldwide and in the U.S. (Salloum et al., 2016; Wang et al., 2018). Despite a few limitations, the publication by Alomari et al., is the first to our knowledge to examine the effects of WP smoking on BDNF and to confirm the link between endothelial dysfunction and impaired cognition that has been identified recently (Marie et al., 2018). Data examining the plausibility of biomarkers to provide a quantitative evaluation of the health effects of WP can inform regulatory efforts aimed at reducing the harms associated with and WP smoking.