According to the present study, decreased serum BDNF levels were observed in drug-naïve MDD patients compared to HCs whereas no significant changes were found when compared between drug-treated MDD patients and HCs. We found a significant negative correlation between the serum BDNF levels with the severity of depression in both drug-treated and non-treated MDD patients. Our results can be described by different hypotheses. One study stated that lower levels of neurotrophic factors have a significant role in the development of depression whereas the increase in serum levels occurs after antidepressant therapy [15]. Another hypothesis is based on BDNF response to different stress mechanisms. Stress may reduce serum BDNF levels which can cause neuronal damage, neuronal atrophy and death in the hippocampus region of the brain result in biological vulnerability [22]. Treatment of MDD patients by antidepressants can increase both the BDNF level and neurogenesis [21]. Karege et al. reported the serum/blood BDNF ratio was lower in MDD compared to HCs and this altered levels of serum BDNF may interfere with the BDNF release mechanisms [23]. Studies proposed that plasma serotonin level is negatively correlated with the severity of depression and decreased levels of serotonin is released in MDD patients [24]. Another research suggested that BDNF in plasma is mainly stored in platelets and their release is correlated with each other, as a result, there is a correlation between serum BDNF levels with serotonin and depression [23,24].
The present study results are consistent with the many previous studies. Karege et al. observed serum BDNF levels were significantly lower in MDD patients compared to HCs. Also, the levels were negatively correlated to the severity scores and the female patients were high severity scores and low BDNF levels than men [15,23]. Bocchio-Chiavetto et al. found significantly decreased serum BDNF levels, but not plasma, in MDD patients than those of HCs [25]. Another study found that plasma BDNF levels were significantly lower in MDD patients than in the HCs [26]. Ozan et al. found MDD patients had a lower serum BDNF level than HCs and male subjects had a higher serum BDNF level than female subjects [27]. Yoshida et al. reported that serum levels of mature BDNF, but not proBDNF, were significantly lower in MDD patients than those of HCs [28]. Another recent study revealed that serum BDNF levels were significantly reduced in MDD patients compared to HCs [29]. Gupta et al. stated that after the treatment of MDD patients with fluoxetine and agomelatine, the serum BDNF levels were increased [30]. Serum BDNF levels were significantly decreased compared to HCs in MDD patients with bipolar symptoms [31]. Moreover, one study found that serum BDNF was significantly decreased in the drug-naive MDD patients than in the antidepressant treated MDD patients or in the HCs [32]. Additionally, many studies reported that the elevation of serum BDNF levels was observed after antidepressant treatment in MDD patients compared to HCs. One recent study suggested that low serum BDNF levels were associated with MDD and after the treatment with escitalopram positive effect was found [33]. According to Matrisciano et al. serum BDNF levels in MDD patients were lower than HCs and after 5 weeks of treatment with sertraline, serum BDNF levels were increased significantly [34]. Lener et al. predicted that the antidepressant action of ketamine increases the serum levels of BDNF in depression [35].
Similar to depression, some researchers observed an association of serum BDNF levels with anxiety and stress. One study found decreased serum BDNF levels in post-traumatic stress disorder after trauma compared to HCs [36]. Moreover, some other serum neuropeptides like GDNF, vascular endothelial growth factor, NGF, insulin-like growth factor-I, etc. can also be a pathological identifier of MDD. Diniz et al. found decreased serum GDNF levels in MDD patients compared to HCs [37]. Another study reported MDD patients were detected with significantly lower serum GDNF levels than HCs [38]. A post-mortem and imaging study also reported lower serum levels of GDNF in patients suffering MDD compared to HCs [39]. Also, reduced serum NGF levels were detected in depressed patients compared to HCs [40].
Another important finding of the present study is the ROC-curve analysis which deals with the diagnostic or predictive value of the analyzed parameters. Many past studies measured the serum BDNF levels in MDD patients and identified its association with depression but none of them were evaluated for their accuracy in diagnostic or predictive purpose [15, 31]. In the present study, the ROC-curve was plotted for serum BDNF levels to assess the diagnostic or predictive value in drug-naive MDD patients. The area under the curve for ROC analysis was 0.821 and the cut-off point was detected as 221.05 pg/mL. Higher values were allotted as the disease condition. Sensitivity, specificity, positive predictive value and negative predictive value were 72.4%, 73.1%, 68.3%, and 78.5%, respectively.
The finding of decreased serum BDNF levels in drug-naïve MDD patients may indicate a significant relationship between the pathophysiology of depression and peripheral levels of BDNF. The negative correlation between Ham-D scores and serum BDNF levels in MDD patients can be used as a predictor for the severity of depression. Increased serum BDNF levels in antidepressants treated MDD patients supported the drug-induced expression of peripheral BDNF. Moreover, analyzed serum BDNF levels achieved good diagnostic value for drug-naive MDD patients which can be used as predictors for the assessment of depression risk.
Limitation of the study
To the best of our knowledge, this is the first study regarding the evaluation of serum BDNF levels in MDD patients among the Bangladeshi population though it has few limitations. We didn’t perform pre and post measurement of serum BDNF levels in the same patient set for antidepressant therapy as well as any food intake data was not recorded. These outcomes should be treated as preliminary and further studies with a large and more homogeneous population are required to understand the exact relation between serum BDNF levels and major depression.