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Table 1 Baseline Characteristics of Included Studies

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

Study ID

Patients

Controls

Main significant findings

Author, Year

Country

Study design

BDNF measurement method

Source (serum, plasma)

No. (Type of ED)

Diagnostic Criteria

BDNF levels

(mean ± SD), ng/ml

No

BDNF levels

(mean ± SD), ng/ml

Nakazato et al., 2002

Japan

Cross-sectional

BDNF Emax Immunoassay System kit (Promega, Madison, WI)

Serum

12 (AN-R, AN-BP)

DSM-IV

24.9 ± 6.75

21

61.4 ± 19.5

Lower BDNF levels in AN and BN patients compared to controls

Lower BDNF levels in AN patients compared to BN patients

Positive correlation between BDNF levels and BMI in all subjects

Nakazato et al., 2002

Japan

Cross-sectional

BDNF Emax Immunoassay System kit (Promega, Madison, WI)

Serum

18 (BN)

DSM-IV

38.4 ± 15.3

21

61.4 ± 19.5

Nakazato et al., 2006

Japan

Longitudinal

BDNF Emax Immunoassay System kit (Promega, Madison, WI, USA)

Serum

13 (AN-R, AN-BP)

DSM-IV

14.5 ± 4.4

17

14.5 ± 4.4

Lower BDNF levels in AN patients compared to controls

No difference in BDNF levels in AN patients before and after partial weight recovery

Positive correlation between BDNF levels and ED symptom scores (EDI-2) in all subjects

Positive correlation between BDNF levels and BMI in all subjects

Nakazato et al., 2009

Japan

Cross-sectional

Emax Immunoassay System kit (Promega, Madison, WI, USA)

Serum

29 (AN-R, AN-BP)

DSM-IV

11.7 ± 4.9

28

15.1 ± 5.5

Lower BDNF levels in AN patients compared to controls

Lower BDNF levels in AN patients compared to patients who recovered from AN

Higher rate of set-shifting errors (WCST) in AN patients

No correlation between BDNF levels and WCST performance

Yamada et al., 2012

Japan

Cross-sectional and longitudinal

ELISA kit (Quantikine, R & D Systems, Minneapolis, MN, USA)

Plasma

16 (BN)

DSM-IV

1.89 ± 1.67

10

6.57 ± 6.09

Lower BDNF levels in BN patients compared to controls

Increased BDNF levels following inpatient treatment, suggesting that lower BDNF in BN is associated with abnormal eating behaviors, especially binge eating

Dmitrzak-Weglarz et al., 2013

Poland

Cross-sectional

DuoSet ELISA Development Kits (R&D Systems) –

Serum

46 (AN-R)

ICD-10 and DSM-IV

23.72955 ± 8.245963

45

22.22206 ± 5.938468

No difference in BDNF levels in AN patients compared with controls

No correlation between BDNF levels and BMI or severity of depression symptoms (BDI) in all subjects

Correlations between BDNF levels and patient personality dimensions (TCI)

Dmitrzak-Weglarz et al., 2013

Poland

Cross-sectional

DuoSet ELISA Development Kits (R&D Systems) –

Serum

14 (AN-BP)

ICD-10 and DSM-IV

23.32821 ± 8.078747

45

22.22206 ± 5.938468

Zwipp et al., 2014

Germany

Cross-sectional and longitudinal

Enzyme-Linked Immunosorbent Assay kits (ELISA; 181 Promega Inc., Madison, WI, USA)

Serum

55 (AN)

DSM-IV

6.6165 ± 3.4158

52

6.7008 ± 2.7814

Higher BDNF levels in patients who recovered from AN compared to acutely underweight AN patients

Increased BDNF levels with short-term weight gain in acutely underweight AN patients

Inverse association of BDNF with psychomotor speed (TMT) in acutely underweight AN patients but not in controls

Acutely underweight AN patients with higher BDNF also had lower lifetime BMI, indicating that serum BDNF levels in patients with AN vary with the stage of illness

Changes in BDNF levels may have different context-dependent effects, including the modulation of cognitive functioning in acutely underweight patients; as BDNF has pleiotropic functions

Eddy et al., 2015

USA

Cross-sectional

immunoassay (ELISA, R&D Systems, Inc)

Serum

50 (AN-R)

DSM-V

13.6 ± 0.9

22

14.6 ± 0.8

Higher BDNF levels in AN-BP than AN-R

No difference in BDNF levels in AN-BP compared to AN-R after controlling for BMI

No difference in BDNF levels in AN patients compared to controls

No correlation between BDNF levels and BMI in all subjects

Positive association between BDNF levels and frequency of purging in all subjects

Eddy et al., 2015

USA

Cross-sectional

immunoassay (ELISA, R&D Systems, Inc)

Serum

25 (AN-BP)

DSM-V

17.2 ± 1.5

22

14.6 ± 1.4

Homan et al., 2015

Switzerland

Randomized, double-blind, placebo-controlled, crossover study

BDNF Emax Immunoassay Kit (Promega, Switzerland)

Plasma

20 (Remitted BN)

DSM-IV

3.058 ± 1.5066

27

2.383 ± 1.2814

Positive correlation between AMPT–induced differences in BDNF levels with the AMPT–induced differences in reward learning across sample

Higher BDNF levels in patients with remitted BN compared to controls across conditions

Higher BDNF levels in the morning before compared with after a standardized breakfast across groups and conditions

Rybakowski et al., 2017

Poland

Longitudinal

n/a

Serum

76 (AN)

n/a

28.94 ± 7.19

30

34.66 ± 7.4

Lower BDNF levels in acute AN

Normalization of BDNF levels after weight recovery in AN

Negative correlation between BDNF levels and body weight in acute AN but not AN after partial weight recovery

No correlation between BDNF levels and psychopathological symptoms (HDRS, BDI and YBOCS) in either acute AN or AN after partial weight recovery

No evidence found to support a role of serum BDNF levels in the modulation of depressive and obsessive–compulsive symptoms of AN

Matsumoto et al., 2017

Japan

Cross-sectional

Human BDNF ELISA kits (Aviscera Bioscience, Santa Clara, CA, USA)

Serum

19 (AN-R, AN-BP)

DSM-IV

13.96 ± 6.02

22

16.58 ± 3.5

No difference in proBDNF and mBDNF levels among AN patients, BN patients, and controls

Correlation between proBDNF and MMP-9 levels in both ED patients and controls

Positive correlation between mBDNF levels and IGT performance in BN patients but not in AN patients

Matsumoto et al., 2017

Japan

Cross-sectional

Human BDNF ELISA kits (Aviscera Bioscience, Santa Clara, CA, USA)

Serum

28 (BN)

DSM-IV

14.99 ± 4.9

22

12.57 ± 12.54

Mancuso et al., 2020

USA

Cross-sectional

ELISA (EMD Millipore: Billerica, MA)

Serum

36 (AN-R, AN-BP)

K-SADS PL and EDE

2.7313 ± 0.4153

32

3.7928 ± 0.4575

Lower fasting BDNF levels in AN patients compared with controls

Lower BDNF AUC after breakfast in AN patients compared with controls

Positive association between BDNF AUC and kilocalories consumed during CTT in AN patients (particularly AN-R)

Tyszkiewicz-Nwafor et al., 2020

Poland

Longitudinal

BDNF DuoSet (cat. No DY 248) and TrkB DuoSet (cat. No DY 397–5) ELISA Development Kit (R&D System, Minneapolis, MN, USA)

Serum

42 (AN)

ICD-10, DSM-IV and DSM-V

28.66 ± 6.7

30

34.66 ± 7.4

Increased BDNF levels in AN patients after partial weight recovery compared with before, but lower levels compared with controls at two-time points

Negative correlation between BDNF levels and the severity of ED symptoms (EAT-26)

No correlation between BDNF levels and depressive and obsessive–compulsive symptoms (HDRS, BDI, YBOCS) for either malnourished patients or partially weight recovered AN patients

Borsdorf et al., 2021

Germany

Longitudinal

Quantikine ELISA (R&D Systems Inc.)

Serum

149 (AN)

DSM-IV

17.36 ± 6.57

79

14.08 ± 0.75

Lower BDNF levels in AN patients at admission compared with controls

Continuous increase in BDNF levels, reaching supranormal levels at 2.5-year follow-up

Inverse association between BDNF levels with ED psychopathology (BDI-II, SCAS, MROAS, SIAB-EX) at discharge

Positive association between BDNF levels with previous weight gain at 1-year follow-up

Keeler et al., 2022

UK

Cross-sectional

U-PLEX Human BDNF assay (Meso Scale Discovery, Maryland, USA)

Serum

56 (AN-R, AN-BP)

DSM-V

5.354 ± 2.616

51

8.323 ± 2.595

Lower BDNF levels in AN patients compared to controls and patients recovering from AN

Negative association of BDNF with depression and ED psychopathology in the whole sample, but not in AN patients

BDNF serum concentrations may be a state marker of AN, but do not reflect symptom severity

In acute AN, BDNF levels seem to be linked to TNF-α signaling

  1. BDNF: Brain-Derived Neurotrophic Factor; proBDNF: precursor Brain-Derived Neurotrophic Factor; mBDNF: mature Brain-Derived Neurotrophic Factor; ED: Eating Disorder; AN: Anorexia Nervosa; BN: Bulimia Nervosa; AN-R: Anorexia Nervosa Restricting subtype; AN-BP: Anorexia Nervosa Binge-eating/Purging subtype; YFAS: Yale Food Addiction Scale; ELISA: Enzyme-Linked Immunosorbent Assay; BMI: Body Mass Index; DSM: Diagnostic and Statistical Manual of Mental Disorders; ICD: International Classification of Diseases; K-SADS PL: Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version; EDE: Eating Disorder Examination; HDRS: Hamilton Depression Rating Scale; BITE: Bulimic Investigatory Test, Edinburgh; EDI: Eating Disorder Inventory; WCST: Wisconsin Card Sorting Test; TCI: Temperament and Character Inventory; TMT: Trail Making Test; AMPA: Alpha-methyl-para-tyrosine; MMP: Matrix Metalloproteinase; IGT: Iowa Gambling Task; SNP: Single Nucleotide Polymorphism; AUC: Area Under Curve; CTT: Cookie Taste Test; EAT: Eating Attitudes Test; BDI: Beck Depression Inventory; YBOCS: Yale-Brown Obsessive–Compulsive Scale; SCAS: Spence Children’s Anxiety Scale; MROAS: Morgan–Russell Outcome Assessment Schedule; SIAB-EX: Structured Interview for Anorexia and Bulimia-Expert Interview