We measured serum BDNF in a large cohort of nonoverweight and overweight children to examine the importance of demographic and auxologic factors as predictors of circulating BDNF. Because conditions that are often associated with energy restriction, such as anorexia nervosa (12
), bulimia nervosa (13
), and untreated major depression (10
), have been found to be associated with low serum BDNF and because serum BDNF has been reported to reflect central BDNF levels in rats (29
), we hypothesized that serum concentrations of BDNF would be positively related to BMI or body adiposity. Contrary to our initial hypothesis, children’s serum BDNF concentrations were not significantly associated with BMI, BMI-Z, or fat mass in univariate models, and in multivariate models, in which chronological age and platelet count (22
) were the strongest factors associated with fasting serum BDNF concentrations, we found a negative association between BDNF and measures of adiposity, such that BDNF concentrations, adjusted for sex, race, pubertal status, age, and platelet count, were 15% lower in severely overweight youth than in those of normal weight. These results differ from those of Nakazato et al.
), who reported a significant, positive relationship between BMI and serum BDNF in adults but only when patients with anorexia nervosa were included in the analysis. Within the group of normal-weight individuals studied, a positive relationship between BMI and BDNF was not found. Interestingly, adults in the study by Nakazato et al.
who had bulimia nervosa, whose weight did not differ from those of his healthy controls, had lower BDNF, a result that may be consistent with the findings reported in the present investigation for severely obese children. Eating-disordered psychopathology involving loss of control over eating may be reported by as many as 30% of such children (31
). Alternatively, it is possible that some extremely overweight children may have relative deficiencies of BDNF and, like the BDNF haploinsufficient mouse (4
), may have hyperphagia as a consequence of BDNF insufficiency. Further studies seeking function-altering mutations in the BDNF gene among severely overweight children with low serum BDNF would thus seem indicated.
We also conducted a pilot investigation of the effect of food intake on serum BDNF 1 h after food consumption. In rats that have undergone a percussive head injury, a 4-wk exposure to a high-fat sucrose diet suppresses BDNF synthesis in some hippocampal neurons (37
). However, in the present study of children, eating a meal did not acutely change serum BDNF. We therefore conclude that circulating BDNF concentrations in children are not rapidly affected by food intake. We hypothesize that the reason we saw relatively little impact of food intake on BDNF concentrations is because serum BDNF most closely reflects platelet stores rather than neuronal secretion of BDNF. It remains possible, however, that serum BDNF might require a longer time period before the effects of food intake might be detected. It is also possible that some individuals have substantial circulating quantities of pro-BDNF, which cross-reacts with all currently available BDNF assays and might thus have affected these results (38
BDNF serves as a neurotransmitter modulator and participates in plasticity mechanisms such as long-term potentiation (39
) and learning (40
). Serum BDNF has therefore previously been investigated in children with autistic disorders and mental retardation (15
). Miyazaki et al.
) reported high serum BDNF in a small group of children with autistic disorders and mental retardation, compared with adult controls. Additional studies comparing serum BDNF in overweight children without neurocognitive difficulties and age- and BMI-matched children who have well-characterized learning and/or mood problems are required to elucidate the relationship between serum BDNF and neurocognitive deficiencies in children.
In conclusion, serum BDNF is not positively related to body adiposity in youth aged 3–19 yr. The current investigation suggests that serum BDNF is positively associated with platelet count and negatively associated with both BMI and age. Thus, serum BDNF concentrations in children may need to be interpreted with age-specific and platelet count-specific standards.
Prospective studies of individuals with phenotypes that include childhood-onset obesity in combination with learning or mood disorders are needed to define the role of serum BDNF as a biological marker for abnormalities in the BDNF-TrkB signal transduction system. Mutations in the BDNF
genes that can be shown to be associated with overweight appear to be rare in obese children (9
). It remains to be determined whether individuals with mutations expected to change BDNF expression or function have significant alterations in serum BDNF or whether serum BDNF will be useful to identify individuals anticipated to have resistance to the actions of BDNF at its receptor.