Is Serum BDNF Altered in Acute, Short- and Long-Term Recovered Restrictive Type Anorexia Nervosa?

Abstract

Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in the regulation of food intake and body weight, has been implicated in the development and maintenance of Anorexia nervosa (AN). The majority of previous studies reported lower BDNF levels in acutely underweight AN patients (acAN) and increasing levels after weight rehabilitation. Here, we investigated serum BDNF concentrations in the largest known AN sample to date, both before and after weight restoration therapy. Serum BDNF was measured in 259 female volunteers: 77 in-patient acAN participants of the restrictive type (47 reassessed after short-term weight rehabilitation), 62 individuals long-term recovered from AN, and 120 healthy controls. We validated our findings in a post-hoc mega-analysis in which we reanalyzed combined data from the current sample and those from our previous study on BDNF in AN (combined sample: 389 participants). All analyses carefully accounted for known determinants of BDNF (age, sex, storage time of blood samples). We further assessed relationships with relevant clinical variables (body-mass-index, physical activity, symptoms). Contrary to our hypotheses, we found zero significant differences in either cross-sectional or longitudinal comparisons and no significant relationships with clinical variables. Together, our study suggests that BDNF may not be a reliable state- or trait-marker in AN after all.

BDNF levels in adolescent patients with anorexia nervosa increase continuously to supranormal levels 2.5 years after first hospitalization

“…The increase in BDNF over the course of weight rehabilitation and recovery fits well with the pre-existing literature. 22,23,[27][28][29] This increase has been interpreted by previous authors as a reconstruction process, indicating repair mechanisms and reversal of damage induced by starvation. 17,23 However, this explanation does not appear to capture the whole process, because it does not explain our new finding of a supranormal endpoint at 2.5-year follow-up.…”

“…The nominally lower cBDNF values we found at admission point in the same direction as a previous, similarly powered meta-analysis by Brandys and colleagues, 17 which found significantly lower serum BDNF values in 155 mostly adult patients with acute anorexia nervosa compared to healthy controls. However, 4 recent studies did not find significant differences in a total of 209 adolescents and 72 adults [21][22][23][24] (but see divergent results [25][26][27] ). This raises the possibility that BDNF reduction might not be as pronounced in adolescent patients with anorexia nervosa, who tend to be less chronically ill. We could neither support nor dismiss this explanation, because we found no correlation between cBDNF and duration of illness in our study.…”

“…17 However, recent studies have painted a more ambiguous picture. Dmitrzak-Weglarz and colleagues (n = 60), 21 Steinhäuser and colleagues (n = 77) 22 and Zwipp and colleagues (n = 72) 23 found no significant differences between patients with acute anorexia nervosa and healthy controls in a population consisting mostly of adolescents. Eddy and colleagues (n = 72) 24 found no significant differences between adults with anorexia nervosa and healthy controls.…”

“…Whether serum BDNF levels normalize in recovered patients with anorexia nervosa (as would be expected) or instead rise to supranormal levels that are significantly higher than that of healthy controls appears less clear. Four studies found nominal increases of 4% to 26% in recovered patients with anorexia nervosa compared to healthy controls, but these increases reached only trend level or were not significant, 22,23,28,29 while Tyszkiewicz-Nwafor and colleagues 27 found that BDNF levels were still decreased after only partial weight recovery. Thus, there have been indications of an increase in serum BDNF to supranormal levels in recovered patients with anorexia nervosa, but previous studies have lacked the power to provide a definitive answer.…”

“…Regarding BDNF after weight recovery, 3 of 4 studies that have done cross-sectional comparisons of patients with anorexia nervosa found that patients who had recovered showed significantly higher BDNF levels than those who were acutely ill 23,28,29 (but see Steinhäuser and colleagues, 22 who found no difference). Five longitudinal studies of shortterm weight-recovered patients with anorexia ner-vosa 22,23,[27][28][29] supported these findings, but only with partly trend-level findings and often small sample sizes.…”