title: 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.
authors.affiliation: 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.
authors.forename: Maria
authors.initials: M
authors.lastname: Giese
authors.affiliation: Center for Affective, Stress and Sleep Disorders, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Beck
authors.affiliation: Center for Affective, Stress and Sleep Disorders, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Serge
authors.initials: S
authors.lastname: Brand
authors.affiliation: Center for Affective, Stress and Sleep Disorders, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Flavio
authors.initials: F
authors.lastname: Muheim
authors.affiliation: Psychiatric Service Center St. Gallen, Wil, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hemmeter
authors.affiliation: Psychiatric Services Solothurn, Department of Adult Psychiatry, Solothurn, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Hatzinger
authors.affiliation: Center for Affective, Stress and Sleep Disorders, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Edith
authors.initials: E
authors.lastname: Holsboer-Trachsler
authors.affiliation: 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.
authors.forename: Anne
authors.initials: A
authors.lastname: Eckert
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002940:Circadian Rhythm / Q000502:physiology*; D003865:Major Depressive Disorder / Q000097:blood* / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D011569:Psychiatric Status Rating Scales; D012892:Sleep Deprivation; D011795:Surveys and Questionnaires; D013997:Time Factors; D055815:Young Adult
chemical_list: D000929:Antidepressive Agents, Tricyclic; D019208:Brain-Derived Neurotrophic Factor; D008803:Mianserin; D000078785:Mirtazapine
keywords: BDNF; Depression; Sleep deprivation; Therapy response