Table 1. Characteristics of studies evaluating the relation between BDNF levels/gene polymorphism and FM.
| Author | Year | Design | Location | FM | Control | N total | N FM | Age | BMI | % Female | Main Findings | Source |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alves et al. | 2020 | Cross-sectional | Brazil | Previous diagnosis of FM in women older than 18 according to 2016 ACR criteria | No chronic pain, FM, systemic lupus erythematosus, arthrosis, rheumatoid arthritis, or use of antidepressant drugs | 216 | 108 | 49.8 ± 9.5 | 27.6 ± 4.8 | 100 | The frequency of the Val allele was significantly higher in patients with FM (90.3%) compared to controls (83.8%) (P = 0.045). | Gene |
| Bidari et al. | 2022 | Case-control | Iran | New diagnosis of FM according to 2016 ACR criteria | Non-FM chronic pain and no concurrent diagnosis of FM | 73 | 50 | 46.7 ± 10.2 | NR | 100 | Patients with FM tended to have lower serum BDNF levels compared to controls (5293.5 ± 2676.3 pg/ml vs. 6136.3 ± 4037.6; P = 0.77). | Serum |
| Cardinal et al. | 2019 | Cohort | Brazil | FM diagnosis according to 2016 ACR and VAS ≥50mm on most days of the last three months | Absence of any diagnosis of acute or chronic disease or medication use | 45 | 17 | 46.3 ± 11.6 | 26.0 ± 5.0 | 100 | BDNF levels were significantly higher in patients with FM compared to healthy controls (49.82 ± 16.31 ng/ml vs. 18.04 ± 10.19; P<0.001). | Serum |
| Caumo et al. | 2016 | Cross-sectional | Brazil | FM diagnosis according to 2010 ACR criteria | Pain-free controls without the use of medications | 33 | 19 | 42.8 ± 9.7 | 28.1 ± 5.7 | 100 | Higher levels of serum BDNF in patients with FM (50.78 ± 16.06 ng/ml) compared to healthy controls (19.00 ± 8.79). | Serum |
| Deitos et al. | 2018 | RCT | Brazil | FM diagnosis according to 2010 ACR criteria | Pain-free healthy controls | 27 | 17 | 48.0 ± 9.0 | 28.7 ± 6.3 | 100 | Serum BDNF levels were significantly higher in patients with FM compared to healthy controls (49.8 + 16.3 ng/ml vs. 14.8 ± 6.9; P<0.01). | Serum |
| Elkfury et al. | 2021 | Cross-sectional | Brazil | FM diagnosis according to 2010 ACR criteria and VAS ≥ 40mm associated with disability | Pain-free healthy controls without the use of medications | 39 | 20 | - | 27.2 ± 4.7 | 100 | Compared to healthy controls, patients with FM had higher serum BDNF levels (27.5 ± 4.1 ng/ml vs. 23.7 ± 6.2; P = 0.029). | Serum |
| Fawzy et al. | 2015 | Cross-sectional | Egypt | FM diagnosis according to 2010 ACR criteria | Age- and sex-matched healthy volunteers | 50 | 30 | 34.0 ± 1.31 | NR | 86 | Patients with FM had significantly higher levels of BDNF compared to healthy controls (25031.5 ± 3684.29 ng/ml vs. 13526.1 ± 3394.35). | Serum |
| Haas et al. | 2010 | Cross-sectional | Brazil | FM diagnosis according to 2006 ACR criteria | Age- and sex-matched healthy controls | 60 | 30 | 46.3 ± 9.3 | NR | 100 | Higher plasma BDNF levels in patients with FM compared to the control group (167.1 ± 171.2 pg/ml vs. 113.8 ± 149.6; P = 0.049). | Plasma |
| Iannuccelli et al. | 2022 | Cross-sectional | Italy | FM diagnosis according to 2016 ACR criteria | Sex-matched healthy controls | 80 | 40 | 48.2 ± 8.8 | 25.1 ± 2.1 | 50 | BDNF levels were significantly lower in FM patients compared to healthy controls (3.25 ± 1.96 ng/ml vs. 8.5 ± 3.6; P<0.001). | Serum |
| Jablochkova et al. | 2019 | RCT | Sweden | FM diagnosis according to 1990 ACR criteria | Age-matched and pain-free women. | 100 | 75 | 50.0 ± 8.5 | 26.8 ± 4.7 | 100 | Plasma levels of BDNF were significantly higher in patients with FM compared to healthy controls (1553.3 [2323.8] pg/ml vs. 671.6 [2250.2]; P = 0.001). | Plasma |
| Laske et al. | 2007 | Pilot | Germany | FM diagnosis according to 1990 ACR criteria | Controls without known major depression, depressive episode or use of antidepressant | 86 | 41 | 51.2 ± 9.6 | NR | 90.7 | Serum BDNF levels were significantly higher in patients with FM (19.6 ± 3.1 ng/ml vs. 16.8 ± 2.7; P<0.0001). | Serum |
| Martin et al. | 2018 | Case-control | Brazil | FM diagnosis according to 1990 ACR criteria | Chronic pain in the same age group of patients | 24 | 13 | 45.9 ± 4.3 | NR | 100 | In pre-treatment measurement, BDNF plasma concentrations had no significant difference (40.25 ± 16.35 ng/ml in controls and 46.57 ± 13.45 in patients with FM; P = 0.389) | Plasma |
| Nugraha et al. | 2013 | Cross-sectional | Germany | FM diagnosis according to 1990 ACR criteria | Age-matched healthy controls without chronic pain | 55 | 28 | 53.7 ± 1.1 | NR | 100 | BDNF concentration was significantly higher in patients with FM compared to healthy controls (15,557.6 [13218.20] pg/ml vs. 20,814.00 [7,152.75]; P <0.05). | Serum |
| Park et al. | 2018 | Cross-sectional | Korea | FM diagnosis according to 1990 ACR criteria | No history of chronic pain without matching for age or sex | 827 | 408 | 46.8 ± 11.7 | NR | 93.6 | No significant difference was seen in genotype and allele prevalence between patients with FM and healthy controls. | Gene |
| Polli et al. | 2020 | Cross-sectional | Belgium | FM diagnosis according to modified 2010 ACR criteria | Matched for age and physical activity healthy controls | 54 | 28 | 49.9 ± 10.2 | 24.5 ± 4.1 | 100 | BDNF protein expression was significantly higher in patients with FM (17.75 ± 4.48 ng/ml vs. 14.89 ± 3.55; P = 0.003). In addition, no significant between-groups differences were showed in the prevalence of gene polymorphism. No association between polymorphism and protein expression were showed. | Serum and Gene |
| Ranzolin et al. | 2016 | Cross-sectional | Brazil | FM diagnosis according to 2010 and 2016 ACR criteria | Age-matched healthy controls without acute or chronic pain | 130 | 69 | 44.3 ± 6.6 | NR | 100 | Study showed no difference between serum BDNF concentration of patients with FM and healthy controls (FM: 30.8 [21.8–37.1] vs. controls: 30.7 [21.1–35.4]; P = 0.595). | Serum |
| Sarchielli et al.† | 2007 | Cross-sectional | Italy | FM diagnosis according to 1990 ACR criteria | Age-matched controls not taking medications for at least two months | 40 | 20 | 40.8 ± 5.6 | NR | 22.5 | Significantly higher levels of CSF BDNF levels were found in FM patients compared to controls (39.4 ± 6.7 pg/ml vs. 11.3 ± 3.4; P<0.001) | CSF |
| Stefani et al. | 2019 | Cross-sectional | Brazil | FM diagnosis according to 2010 ACR and VAS ≥40mm that lasted more than three months with functional disability | Pain free volunteers without CNS complications | 96 | 79 | - | NR | 100 | Higher BDNF levels were seen in patients with FM compared to healthy controls (41.23 ± 20.03 pg/ml vs. 20.49 ± 8.82). | Serum |
| Taşkin et al. | 2008 | Cross-sectional | Turkey | Previously diagnosed FM | Healthy controls | 45 | 19 | 38.1 ± 7.8 | NR | 86.7 | Non-significant lower levels of BDNF were found in FM patients (30.75 ± 8.94 ng/ml) compared to healthy controls (31.42 ± 8.85). | Serum |
| Xiao et al. | 2012 | Cross-sectional | United states | FM diagnosis according to ACR criteria | Healthy controls that they had not sought medical care because of pain during the previous 5 years | 153 | 95 | 47.3 ± 11.0 | 32.8 ± 9.1 | 89.5 | The study found that genotype and allele frequency were not significantly different between patients with FM and healthy controls. | Gene |
† This study was not included in meta-analyses. FM, fibromyalgia; ACR, American College of Rheumatology; VAS, visual analog scale; BDNF, brain-derived neurotrophic factor; RCT, randomized controlled trial; CSF, cerebrospinal fluid; CNS, central nervous system.