Chronic depression is associated with a pronounced decrease in serum brain-derived neurotrophic factor over time

Abstract

One of the leading neurobiological hypotheses on depression states that decreased expression of brain-derived neurotrophic factor (BDNF) contributes to depression. This is supported by consistent findings of low serum BDNF levels in depressed patients compared with non-depressed controls. Whereas it has been generally assumed that this is a state characteristic of depression, strong inferences about state or trait effects require a longitudinal study design. To investigate the longitudinal association between serum BDNF and depression, we measured serum BDNF, (current and past) depression status, use of antidepressants, and all potential covariates at baseline and after 2 years in 1751 individuals, consisting of patients with an incident (n=153), remitted (n=420) and persistent depression (n=310) and non-depressed controls (n=868). We analyzed change/differences in serum BDNF across these four groups with analyses of covariance adjusted for covariates and baseline BDNF value, together with the effects of starting and stopping antidepressant treatment. Our analyses revealed a significant difference for the depression course groups (P=0.007). Compared with non-depressed controls, persistently depressed and remitted patients had a steeper decrease of BDNF levels over time (-1.33 (P=0.001) and -0.97 ng ml(-1) (P=0.011), respectively), whereas BDNF reductions in patients with incident depression were similar to those in healthy controls. Initiation or discontinuation of antidepressants was not associated with BDNF change (P=0.72). These findings suggest that BDNF not only contributes to depression, but that depression in turn may also contribute to low BDNF.

Relationship Between Hippocampal Volume, Serum BDNF, and Depression Severity Following Electroconvulsive Therapy in Late-Life Depression

“…Differences in the sBDNF level could also be explained by sample characteristics and protocols used (eg, urbanicity, sex, smoking status, time of blood withdrawal, and so on; Bus et al, 2011). Similar to the observation from a large longitudinal study showing that initiation or discontinuation of antidepressants is not associated with sBDNF change (p = 0.72; Bus et al, 2015), we did not find any differences between the subjects who continued antidepressant therapy with the non-medicated sample.…”

“…Although BDNF can have a crucial role in the development of depression and its recovery (Molendijk et al, 2013;Bus et al, 2012Bus et al, , 2015, our study seems to indicate that improvements in depression and sBDNF are unrelated. The inability to elevate sBDNF levels following ECT could be because of an age-related less responsive BDNF system (Calabrese et al, 2013;Rapinesi et al, 2015).…”

Role of Serum Brain Derived Neurotrophic Factor and Central N-Acetylaspartate for Clinical Response under Antidepressive Pharmacotherapy

“…Although contrary to the neurotrophin hypothesis, this is in line with several recent studies that do not show a BDNF increase over the course of antidepressant treatment and other studies that also reported a clinical response to treatment without BDNF increase [18,22] or BDNF variations, independent of continuous application of antidepressants [47,48,49]. Our results were found while controlling for age and sex.…”

“…In contrast to most studies that assess BDNF in an acute state or for a few weeks under medication, there are some studies that argue that low peripheral BDNF might be associated with a chronic rather than an initial depressive state [24,47]. Bus et al [47] showed that over two years, serum BDNF persistently decreased in a group of depressed patients independently of remission and antidepressant treatment.…”

“…Bus et al [47] showed that over two years, serum BDNF persistently decreased in a group of depressed patients independently of remission and antidepressant treatment. Furthermore, in this depressed group, they found a steeper serum BDNF decrease compared to healthy controls and initially depressed subjects.…”