Partial Normalization of Serum Brain-Derived Neurotrophic Factor in Remitted Patients after a Major Depressive Episode

Abstract

We had previously reported decreased serum brain-derived neurotrophic factor (BDNF) levels in depressed patients. In the present study, we tested the hypothesis that antidepressant treatment would normalize serum BDNF levels, at least in a subgroup of patients. Major depressed patients (15 females and 11 males) diagnosed according to DSM-IV criteria and healthy controls (13 females and 13 males) participated in this study. Serum BDNF was assayed with the ELISA method for depressed and remitted patients and the severity of depression was evaluated with the Montgomery-Asberg Depression Rating Scale. An analysis of variance showed that treatment had an effect [F(1, 24) = 4.46, p = 0.045] on the normalization of serum BDNF levels. We also found a correlation between the severity of depression (r = 0.51, p = 0.008), the pretreatment BDNF levels (r = 0.62, p = 0.001) and the difference in serum BDNF levels after antidepressant treatment. These results suggest that antidepressant treatment has a positive effect on serum BDNF levels and support the hypothesis of neurotrophic factor involvement in affective disorders.

Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

“…Given that IFN-a therapy is associated with higher IL-6 in those who develop MDD (Prather et al, 2009) and IL-6 can induce lymphocytes to increase BDNF production (Kunz et al, 2009), the parsimonious explanation for lowering serum BDNF during IFN-a therapy is that it is a consequence of decreased CNS BDNF (rather than decreased peripheral synthesis) (Lisak et al, 2007). In support of this, BDNF can readily cross the blood-brain barrier via a high-capacity transport system (Pan et al, 1998;Poduslo and Curran, 1996), serum BDNF correlates with cortical BDNF mRNA expression (Gervasoni et al, 2005), and serum BDNF may be affected by changes in cortical BDNF. For example, electroconvulsive treatments result in increased cortical BDNF followed by a rise in serum BDNF (Sartorius et al, 2009).…”

“…Thus, it is feasible that cytokine-induced decreases in BDNF may result in the depressogenic effects of inflammatory cytokines such as IFN-a. Consistent with this, several studies have associated low serum BDNF with MDD (Aydemir et al, 2006;BocchioChiavetto et al, 2006;Gervasoni et al, 2005;Hashimoto, 2010;Sen et al, 2008;Shimizu et al, 2003;Verhagen et al, 2010), which subsequently normalizes with antidepressant treatment (Castren and Rantamaki, 2010;Chen et al, 2001). Also, a functional polymorphism causing a change from valine (Val) to methionine (Met) may result in diminished BDNF secretion (Egan et al, 2003).…”

Consensus paper of the WFSBP Task Force on Biological Markers: Biological Markers in Depression

“…All of these treatments increase BDNF at least in rats, and likely in humans, as supported by multiple threads of evidence, e.g., direct measurements of BDNF in the bloodstream (Karege et al 2002(Karege et al , 2005Shimizu et al 2003). Treatment of depressed patients with antidepressants increases the reduced pretreatment serum BDNF levels close to the levels of normal controls (Aydemir et al 2005;Gervasoni et al 2005;Gonul et al 2005). Some results suggest that the combination of exercise and antidepressant treatment may have significant neurochemical and behavioural effects.…”

Interaction between BDNF and Serotonin: Role in Mood Disorders

“…The resultant decrease in activity in excitatory neurons could underlie the observed downregulation of BDNF. Moreover, several studies have shown that SSRI treatment, which increases synaptic serotonin levels, can reverse the stress-induced downregulation of BDNF gene expression (Aydemir et al, 2005;Gervasoni et al, 2005;Gonul et al, 2005). In summary, stress generally inhibits BDNF gene expression, and some evidence suggests that this effect is, at least in part, mediated by a reduction in serotonin signaling.…”