Prognostic effect of serum BDNF levels in late-life depression: Moderated by childhood trauma and SSRI usage?

M Dimitriadis,R.H.S Van Den Brink,H.C Comijs,R.C Oude Voshaar

doi:10.1016/j.psyneuen.2019.02.003

M Dimitriadis, R.H.S Van Den Brink + Show 2 more

Open Access

https://doi.org/10.1016/j.psyneuen.2019.02.003

Copy DOI

Journal: Psychoneuroendocrinology	Publication Date: Feb 7, 2019
Citations: 9	License type: cc-by

Affiliation: University of Groningen

Abstract

BackgroundBrain-derived neurotrophic factor (BDNF) levels decline during depression and normalise after remission, although studies in older patient samples are inconsistent. Whether BDNF serum levels predict depression remission is unclear. We hypothesize that the predictive value of serum BDNF levels in late-life depression is moderated by selective serotonin reuptake inhibitors (SSRI) usage and early traumatization. MethodsOur study sample was a subset of the Netherlands Study of Depression in Older persons (NESDO), a prospective cohort study. It consisted of 267 older persons with a diagnosis of depression, for which follow-up data were available. Depression diagnosis was assessed at baseline and follow up using a structured diagnostic interview (Composite International Diagnostic Interview (CIDI), volume2.1). Logistic regression was performed (adjusted for covariates) with remission of depression after two years as the dependent variable and baseline BDNF serum levels, childhood traumatization and SSRI use as independent variables. Results - The mean age of the subjects was 70.7 years, 65.6% of them were female, their mean BDNF level was 7.7 ng/ml, 80 (30.0%) of them were traumatised in their childhood,71 (26.6%) used SSRIs and 136 (50.9%) no longer had a depressive disorder at the two year follow up. The predictive value of BDNF serum levels was conditional on traumatization and SSRI usage (threeway interaction p = .010). Higher BDNF serum levels predicted remission in traumatized depressed patients without SSRI usage (OR = 1.17, 95% C.I.: 1.00–1.36; p = .048) and in non-traumatized depressed patients who used SSRIs (OR = 1.17, 95% C.I.: 1.00–1.36; p = .052), but not in the other two subgroups. ConclusionThe association between BDNF serum levels and the course of late-life depression seems to depend on SSRI use and childhood trauma. Based on these results, we hypothesize that childhood trauma may permanently reduce (‘blunt’) the responsiveness of the neurotrophic system to SSRI usage, and that this responsiveness might be more important for depression course than the actual BDNF serum levels.

Highlights

The neurotrophic hypothesis of depression postulates that a stressinduced reduction of neurotrophic support, predisposes an individual to depression (Duman et al, 1997)
Five studies have been confined to late life depression; three of them found signifficantly decreased serum Brain-derived neurotrophic factor (BDNF) levels in depressed patients compared to non-depressed controls, (Chu et al, 2012; Diniz et al, 2010; Laske et al, 2010; Shi et al, 2010), whereas the fifth study did not
We found that the impact of BDNF serum levels on remission of late-life depression was moderated by the combination of the presence of early childhood traumatization and selective serotonin reuptake inhibitors (SSRI) usage

Summary

Introduction

The neurotrophic hypothesis of depression postulates that a stressinduced reduction of neurotrophic support, predisposes an individual to depression (Duman et al, 1997). Metaanalyses concluded that these results need further replication in studies with larger patient samples (Molendijk et al, 2014; Polyakova et al, 2015), and that BDNF serum levels may not be sufficient to predict depression remission. Brain-derived neurotrophic factor (BDNF) levels decline during depression and normalise after remission, studies in older patient samples are inconsistent. We hypothesize that the predictive value of serum BDNF levels in late-life depression is moderated by selective serotonin reuptake inhibitors (SSRI) usage and early traumatization. Logistic regression was performed (adjusted for covariates) with remission of depression after two years as the dependent variable and baseline BDNF serum levels, childhood traumatization and SSRI use as independent variables. Conclusion: The association between BDNF serum levels and the course of late-life depression seems to depend on SSRI use and childhood trauma. We hypothesize that childhood trauma may permanently reduce (‘blunt’) the responsiveness of the neurotrophic system to SSRI usage, and that this responsiveness might be more important for depression course than the actual BDNF serum levels

Methods

Results

Discussion

Conclusion