Serum BDNF levels before treatment predict SSRI response in depression

Abstract

OBJECTIVES The “neurotrophin hypothesis” of depression posits a role of brain-derived neurotrophic factor (BDNF) in depression, although it is unknown whether BDNF is more involved in the etiology of depression or in the mechanism of action of antidepressants. . It is also unknown whether pre-treatment serum BDNF levels predict antidepressant response. METHODS Thirty un-medicated depressed subjects were treated with escitalopram (N=16) or sertraline (N=14) for eight weeks. Twenty-five of the depressed subjects completed 8 weeks of antidepressant treatment and had analyzable data. Twenty-eight healthy controls were also studied. Serum for BDNF assay was obtained at baseline in all subjects and after 8 weeks of treatment in the depressed subjects. Depression ratings were obtained at baseline and after 8 weeks of treatment in the depressed subjects. RESULTS Pre-treatment BDNF levels were lower in the depressed subjects than the controls (p= 0.001) but were not significantly correlated with pre-treatment depression severity. Depression ratings improved with SSRI treatment (p< 0.001), and BDNF levels increased with treatment (p= 0.005). Changes in BDNF levels were not significantly correlated with changes in depression ratings. However, pre-treatment BDNF levels were directly correlated with antidepressant responses (p<0.01), and “Responders” to treatment (≥ 50% improvement in depression ratings) had higher pre-treatment BDNF levels than did “Non-responders” (p< 0.05). CONCLUSIONS These results confirm low serum BDNF levels in unmedicated depressed subjects and confirm antidepressant-induced increases in BDNF levels, but they suggest that antidepressants do not work simply by correcting BDNF insufficiency. Rather, these findings are consistent with a permissive or facilitatory role of BDNF in the mechanism of action of antidepressants.

The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

“…The inhibition of serotonin uptake may be substantial in the anti-inflammatory effect of antidepressants [12,40,41]. Moreover, escitalopram can elevate the serum level of BDNF in depressed patients as reported in a previous study [42]. These findings are in agreement with various published data in which escitalopram was individually efficacious in decreasing depression symptoms in comparison with placebo [43,44].…”

Neurotrophic factors in depression in response to treatment

“…We have also performed these analyses and observed no significant correlations between changes in MADRS depression score and changes in serum BDNF or VEGF levels. This finding is in agreement with some studies (Ventriglia et al, 2009;Wolkowitz et al, 2011;Yoshimura et al, 2014) and in disagreement with others (Iga et al, 2007;Matrisciano et al, 2009;Minelli et al, 2014).…”

“…Although not directly comparable, this is in harmony with our previous study (Elfving et al, 2012) showing a significantly higher serum BDNF level in depressed individuals compared to controls and is further supported by a recent metaanalysis showing no significant difference in BDNF concentrations among healthy controls and antidepressant treated depressed patients (Molendijk et al, 2014). Most studies have reported a significant increase in serum BDNF level after antidepressant treatment (Aydemir et al, 2005;Yoshimura et al, 2007Yoshimura et al, , 2014Hellweg et al, 2008;Matrisciano et al, 2009;Wolkowitz et al, 2011;Deuschle et al, 2013), and a few studies have reported a significant decrease (Hellweg et al, 2008;Deuschle et al, 2013). The experimental designs of these studies differ in the type of antidepressant treatment, treatment period, assessment methods, and temperature of serum storage.…”

Effect of Mirtazapine Treatment on Serum Levels of Brain-Derived Neurotrophic Factor and Tumor Necrosis Factor-α in Patients of Major Depressive Disorder with Severe Depression

“…Moreover, some studies say that changes in BDNF levels are associated with treatment response and only responders show altered levels [13,14] , whereas others found no association between BDNF levels and treatment response [15] . Also, some studies did not consider therapeutic response as a potential factor for BDNF levels regulation [16] .…”