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

Maria Giese; Johannes Beck; Serge Brand; Flavio Muheim; Ulrich Hemmeter; Martin Hatzinger; Edith Holsboer-Trachsler; Anne Eckert

doi:10.1016/j.jpsychires.2014.09.005

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

J Psychiatr Res. 2014 Dec:59:1-7. doi: 10.1016/j.jpsychires.2014.09.005. Epub 2014 Sep 16.

Authors

Maria Giese¹, Johannes Beck², Serge Brand², Flavio Muheim², Ulrich Hemmeter³, Martin Hatzinger⁴, Edith Holsboer-Trachsler², Anne Eckert⁵

Affiliations

¹ Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric Clinics of the University of Basel, Basel, Switzerland; Transfacultary Research Platform, Molecular & Cognitive Neuroscience, University of Basel, Basel, Switzerland.
² Center for Affective, Stress and Sleep Disorders, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
³ Psychiatric Service Center St. Gallen, Wil, Switzerland.
⁴ Psychiatric Services Solothurn, Department of Adult Psychiatry, Solothurn, Switzerland.
⁵ Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric Clinics of the University of Basel, Basel, Switzerland; Transfacultary Research Platform, Molecular & Cognitive Neuroscience, University of Basel, Basel, Switzerland. Electronic address: Anne.Eckert@upkbs.ch.

PMID: 25258340
DOI: 10.1016/j.jpsychires.2014.09.005

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Analysis of Variance
Antidepressive Agents, Tricyclic / therapeutic use
Brain-Derived Neurotrophic Factor / blood*
Circadian Rhythm / physiology*
Depressive Disorder, Major / blood*
Depressive Disorder, Major / therapy*
Enzyme-Linked Immunosorbent Assay
Female
Humans
Male
Mianserin / analogs & derivatives
Mianserin / therapeutic use
Middle Aged
Mirtazapine
Psychiatric Status Rating Scales
Sleep Deprivation*
Surveys and Questionnaires
Time Factors
Young Adult

Substances

Antidepressive Agents, Tricyclic
Brain-Derived Neurotrophic Factor
Mianserin
Mirtazapine