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

Abstract

Background: Brain-derived neurotrophic factor (BDNF) influences brain plasticity and feeding behaviour, and it has been linked to anorexia nervosa in numerous studies. Findings in mostly adult patients point to reduced serum BDNF levels in the acute stage of anorexia nervosa and rising levels with weight recovery. However, it is unclear whether this increase leads to normalization or supranormal levels, a difference that is potentially important for the etiology of anorexia nervosa and relapse. Methods: We measured serum BDNF at admission (n = 149), discharge (n = 130), 1-year follow-up (n = 116) and 2.5-year follow-up (n = 76) in adolescent female patients with anorexia nervosa hospitalized for the first time, and in healthy controls (n = 79). We analyzed associations with body mass index, eating disorder psychopathology and comorbidities. Results: Serum BDNF was only nominally lower at admission in patients with anorexia nervosa compared to healthy controls, but it increased continuously and reached supranormal levels at 2.5-year follow-up. BDNF was inversely associated with eating disorder psychopathology at discharge and positively associated with previous weight gain at 1-year follow-up. Limitations: We compensated for attrition and batch effects using statistical measures. Conclusion: In this largest longitudinal study to date, we found only nonsignificant reductions in BDNF in the acute stage of anorexia nervosa, possibly because of a shorter illness duration in adolescent patients. Supranormal levels of BDNF at 2.5-year follow-up could represent a pre-existing trait or a consequence of the illness. Because of the anorexigenic effect of BDNF, it might play an important predisposing role for relapse and should be explored further in studies that test causality.

Serum and plasma levels of brain-derived neurotrophic factor in individuals with eating disorders (EDs): a systematic review and meta-analysis

“…Except for four studies [ 37 , 40 – 42 ], all the other included ones reported a negative association between the level of BDNF and the presence of any type of eating disorders, meaning the levels of BDNF was lower among ED individuals compared to healthy controls (Table 1 ). None of the four studies reported the opposite recruited sex-matched controls.…”

“…None of the four studies reported the opposite recruited sex-matched controls. In fact, except for Borsdorf et al [ 37 ] study, having age-matched controls, the other three studies did not provide information on the detailed characteristics of their control groups.…”

“…The median NOS score for included studies was 6.57 (IQR = 1, mean ± SD = 6.57 ± 0.75, range: 5–8) out of 9, which shows an estimated moderate to good quality. One study (7.14%) [ 43 ] had high risks of bias (scores 0–5), twelve studies (85.71%) [ 36 , 38 – 42 , 44 – 48 ] had moderate [ 34 , 39 ] risks of bias (scores 6–7), and one study (7.14%) [ 37 ] had low risks of bias (scores 8–9) in their methodological quality (Table 2 ).…”

“…An influence analysis was done to detect any influential cases, which identified three studies as outliers [ 37 , 44 , 46 ], and the p-value raised from 0. 0116 to 0.0118.…”

Long-lasting BDNF signaling alterations in the amygdala of adolescent female rats exposed to the activity-based anorexia model

“…Moreover, low BDNF circulating levels have also been reported in other chronic mental disorders, including obsessive-compulsive disorder, major depression, bipolar disorder, and schizophrenia (Bocchio-Chiavetto et al, 2010 ; Fontenelle et al, 2012 ; Brand et al, 2015 ; Fernandes et al, 2015 ), reasonably pointing to BDNF as a potential biomarker of increased vulnerability also in AN. Regarding the modulation of BDNF after weight recovery, different investigations found a normalization of serum BDNF in weight-recovered AN patients (Ehrlich et al, 2009 ; Zwipp et al, 2014 ; Tyszkiewicz-Nwafor et al, 2019 ) or a rise to supranormal levels that are significantly higher than those of healthy controls (Borsdorf et al, 2021 ). Even though the human condition is less clear, body weight recovery in ABA rats restored circulating BDNF levels, suggesting that, in rats, peripheral mechanisms mediating BDNF homeostasis are still able to recover.…”