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

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.

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).

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.

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.