Fast BDNF serum level increase and diurnal BDNF oscillations are associated with therapeutic response after partial sleep deprivation

Abstract

Objective: Preclinical and clinical studies support a role for brain-derived neurotrophic factor (BDNF) in the pathophysiology of stress-related mood disorders. Furthermore, BDNF seems to be linked to antidepressant action. Available pharmacological treatments for depression are characterized by significant limitations with low efficacy and a major delay until treatment response. This demonstrates the urgent need for more efficient and fast-acting antidepressants. Besides ketamine, sleep deprivation (SD) as well as partial sleep deprivation (PSD) are effective and fast-acting antidepressant methods. However, the underlying molecular mechanisms of SD are not well understood; especially possible mechanisms explaining the rapid, but transient antidepressant effect of SD are unknown.

Methods: We evaluated serum BDNF from 28 patients suffering from major depressive disorder (MDD), who were naïve to SD therapy at seven different time points within a 32 h time window before (day 0) and after PSD (day 1). PSD-response was assessed by 6-Items of the Hamilton Depression Rating Scale (HDRS) before (day 0) and at follow-up after 2 weeks (FU2).

Results: PSD induced a very fast increase in BDNF serum levels at day 1 which parallels clinical findings, since levels increased with decreasing depression scores in all participants. Notably, responders showed a significant diurnal BDNF serum variation not only after PSD but already before PSD treatment, while diurnal profile of serum BDNF from non-responders did not vary.

Conclusions: The elasticity in diurnal serum BDNF variation is associated with favourable treatment response to PSD in patients suffering from MDD. Therefore, a normalized BDNF serum profile which oscillates in a circadian fashion seems to precede, rather than follow a favourable treatment outcome in depressed patients. Furthermore the fast increase of BDNF is comparable to effects seen with ketamine infusion.

Keywords: BDNF; Depression; Sleep deprivation; Therapy response.