Table 2.
Studies on circulating BDNF protein levels.
| Study and Country | Study Design | Sample | Study Aim(s) | Main Findings | |
|---|---|---|---|---|---|
| 1 | Aas et al. 2018, Norway [39] | Cross-sectional | 254 BD patients; 589 psychotic patients; 603 HC | To assess BDNF serum levels and to investigate if childhood trauma can affect BDNF levels | Reduced BDNF levels in patients with severe mental disorders. The most substantial reduction was observed in patients reporting childhood sexual abuse. |
| 2 | Ameele et al. 2017, Belgium [54] | Prospective case–control study | 67 BD patients (35 during a depressive and 32 during a manic episode) 30 HC |
To evaluate mood-specific changes in BDNF and their association with inflammatory activity | No differences in the levels of BDNF levels between BD patients and HC. |
| 3 | Barbosa et al. 2010, Brazil [51] | Cross-sectional | 53 BD (34 manic and 19 euthymic) patients 38 HC |
To assess BDNF levels in BD patients and their association with clinical and demographic factors | Significantly increased plasma BDNF levels in patients with mania and euthymia compared to controls, without any correlation with clinical parameters. Higher BDNF concentration in BD patients with 10 or more years of disease was found. |
| 4 | Fernandes et al. 2009, Brazil [58] | Cross-sectional | 40 BD patients 10 MDD patients 30 HC |
To investigate serum BDNF levels as a potential diagnostic biomarker in bipolar and unipolar depression | Lower serum BDNF levels in depressed BD patients compared to MDD patients and controls were found. |
| 5 | Binici et al. 2016, Turkey [53] | Cross-sectional | 25 BD patients 17 HC |
To assess BDNF serum levels in euthymic adolescents with BD type I |
No difference in BDNF levels between patients and healthy controls was found. |
| 6 | Chou et al., 2021, Taiwan [68] | Cross-sectional | 23 euthymic BD type I patients 33 HC |
To examine the cognitive performance in euthymic BD I patients and to assess if cognitive deficits correlate with BDNF levels | No association between impaired cognition and BDNF was found. |
| 7 | Cunha et al. 2005, Brazil [70] | Cross-sectional | 85 BD (32 euthymic, 21 Depressed and 32 Manic) patients 32 HC |
To investigate serum BDNF levels in manic, depressed, and euthymic BD patients and in matched healthy controls | Decreased serum BDNF levels in BD patients during manic and depressive episodes compared with euthymic BD patients and HC. Negative correlation between serum BDNF levels and severity of manic and depressive symptoms was found. |
| 8 | Dias et al. 2009, Spain [67] | Cross-sectional | 65 BD patients 50 HC |
To investigate serum BDNF levels in BD patients compared with HC | No significant difference in serum BDNF levels in BD type I euthymic patients compared to healthy controls. |
| 9 | Jacoby et al. 2016, Denmark [72] | Longitudinal | 60 BD-I patients 35 HC |
To investigate whether neurotrophins and inflammatory markers vary with mood states | BDNF and the other inflammatory markers did not vary according to affective state in adjusted mixed models. |
| 10 | Machado-Vieira et al. 2007, Brazil [61] | Cross-sectional | 60 BD patients 30 HC |
To investigate whether BDNF levels are altered during manic phases of the disorder | Significantly decreased BDNF levels in manic patients compared to HC. Negative correlation between the severity of manic episodes and BDNF plasma levels. |
| 11 | Mansur et al., 2016, Brasile/Canada [66] | Cross-sectional | 57 BD patients 26 HC |
To assess the relationship between BDNF levels and indices of illness course | Lower levels of BDNF in the BD population. |
| 12 | Monteleone et al, 2008, Italy [64] | Cross-sectional | 35 MDD patients 17 BD I patients 11 BD II patients 22 HC |
To assess BDNF circulating levels in mood disorders; to exclude the possibility that comorbid psychiatric disorders exerted an effect on BDNF levels | Serum BDNF levels were reduced in both euthymic and depressed MDD patients as well as in euthymic patients with BD-I and BD-II. The reduction in circulating BDNF was not affected by drug treatments. Comorbid Axis I mental disorders did not influence circulating BDNF in affective patients. |
| 13 | Nuernberg et al., 2016, Brazil [65] | Longitudinal | 236 patients with BD, MDD, SZ 100 HC |
To evaluate BDNF levels at admission and discharge and compare them with HC To compare BDNF levels in the different SMI patients |
BDNF levels persistently lower compared to HC were found. |
| 14 | Oliveira et al., 2009, Brazil [59] | Cross-sectional | 22 BD unmedicated patients, 22 BD medicated patients, 22 HC | To assess whether drug-free patients have different levels of circulating serum BDNF compared to medicated BD patients and controls | Serum BDNF is decreased in drug-free and drug-treated BD subjects during manic and depressive episodes compared with HC. Similar serum BDNF levels in drug-free and medicated BD patients. |
| 15 | Piccinni et al. 2014, Italy [60] | Cross-sectional | 18 depressed patients (16 BD patients, 2 MDD patients) 19 BD patients with mixed episode 15 HC |
To assess BDNF plasma levels in patients with mixed episodes, and compare them with those with a depressed episode and HC | Lower BDNF levels in depressed patients compared to patients with mixed episodes, although the difference was not statistically significant. |
| 16 | Poletti et al. 2016, Italy [52] | Cross-sectional | 36 BD patients 17 HC |
To assess BDNF serum levels in BD patients and HC | Significantly higher serum BDNF levels in BD patients compared with HC were found. |
| 17 | Rosa et al. 2014, UK and Spain [69] | Cross-sectional | 50 BD I patients 50 HC |
To assess BDNF levels in BD I patients compared with HC | Similar levels of plasma BDNF levels in bipolar patients and healthy controls were found. |
| 18 | Shahyad et al. 2023, Iran [56] | Cross-sectional | 30 BD patients 30 MDD patients 30 HC |
To assess the discriminatory properties of BDNF levels for the differential diagnosis of BD and MDD | Lowest BDNF levels in BD compared to MDD or HC. |
| 19 | Skibinska et al. 2021, Poland [55] | Longitudinal | 27 BD patients 52 MDD patients 31 HC |
To assess serum levels of BDNF, proBDNF, mBDFN, and rBDNF | No significant difference in BDNF among patients and controls was found. Higher levels of BDNF in patients with a family history of affective disorders were found. |
| 20 | Teng et al, 2021, Cina [57] | Cross-Sectional | 45 BD II patients 40 MDD patients 40 HC |
To assess the role of BDNF in clinical and cognitive outcomes in medication-naïve patients with BD II and MDD patients | Decreased serum BDNF in MDD and BD II patients with a current depressive episode, compared to HC. BDNF and cognitive deficits are both of low efficiency in distinguishing BD II from MDD. |
| 21 | Tramontina et al, 2009, Brazil [40] | Longitudinal | 10 BD I patients 10 HC |
To assess changes in BDNF serum levels of BD patients during and after treatment of an acute episode | Decreased BDNF levels in BD patients during mania compared to HC. This difference was no longer significant after treatment. A sharp increase in BDNF levels after effective treatment was found. No correlation between BDNF levels either in acute episodes or after treatment with clinical scales was found. |
| 22 | Tunca et al, 2014, Turkey [62] | Cross-Sectional | 96 BD patients (37 euthymic, 33 manic, 26 depressed) 61 HC |
To assess BDNF levels across different episodes in bipolar disorders | Significantly lower BDNF levels during mania and depression compared to euthymic patients and HC. Positive correlation between BDNF levels and lithium levels. |
| 23 | Yoshimura et al, 2006, Japan [63] | Longitudinal | 18 BD I patients (12 manic, 6 depressive) 20 HC |
To investigate the efficacy of risperidone treatment for both acute manic and depressive episodes in BD | Decreased plasma levels of BDNF in depressed patients compared with manic patients or healthy controls. The administration of risperidone did not alter plasma BDNF levels. |
| 24 | Zhao et al, 2017, China [71] | Longitudinal | 24 BD patients 37 MDD patients 44 HC |
To investigate the role of mature BDNF (mBDNF) and its precursor (proBDNF) in distinguishing bipolar depression (BP) from MDD during acute depressive episode | Lower plasma mBDNF levels and mBDNF/proBDNF ratio in BP compared with MDD. The M/P ratio was restored to normal levels after antidepressant treatment in the MDD group. |
BDNF: brain-derived neurotrophic factor; MDD: major depressive disorder; BD: bipolar disorder; HC: healthy controls; SZ: schizophrenia; SMI: severe mental illness; proBDNF: BDNF precursor; mBDNF: mature BDNF; rBDNF: mBDNF/proBDNF ratio; M/P ratio: mBDNF/proBDNF ratio.