Abstract
Background: The neurotrophin hypothesis of depression emphasizes the role of down-regulation of Brainderived Neurotrophic Factor (BDNF) in the pathophysiology of Major Depressive Disorder (MDD). Patients with MDD may have reduced serum BDNF levels and treatment with antidepressants may stimulate the expression of BDNF resulting in normalization of BDNF after successful treatment. Objective: To determine whether serum BDNF in MDD patients is lower than in healthy control (HC) subjects, whether all MDD patients show lower than normal levels and whether MDD patients with comparatively higher BDNF levels will respond better to antidepressant therapy. Method: Ninety medically healthy outpatients diagnosed with MDD were enrolled in one of two studies. In Study-1 patients were treated with escitalopram and in Study-2 with quetiapine. The main outcome measure was the 17-item Hamilton Depression Scale (HAM-D) scores. Of the 90 enrolled patients 54 had baseline BDNF values. Thirteen HC subjects for whom serum BDNF values were available were included for comparison. Results: Mean baseline serum BDNF did not differ between MDD and HC subjects. When the median BDNF value was used as a “cut score” to subdivide the MDD group into an above median (high) and a below median (low) subgroup, significant differences emerged. Both subgroups differed significantly from the HC mean and from each other. Depressive episodes of greater than 6 months’ duration correlated significantly with higher BDNF levels (p=0.03). Higher BDNF levels predicted a high probability of a positive treatment response (p=0.02) to either of the two pharmacologic agents used. Conclusions: Serum BDNF levels can be higher or lower in MDD subjects when compared to healthy controls. A high baseline BDNF level may predict a positive treatment response to antidepressant drug therapy, suggesting a possible future role of serum BDNF level as a useful biomarker for subtyping MDD and predicting antidepressant treatment response.
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