Preliminary Associations Between Brain-Derived Neurotrophic Factor, Memory Impairment, Functional Cognition, and Depressive Symptoms Following Severe TBI

Neurorehabil Neural Repair. 2016 Jun;30(5):419-30. doi: 10.1177/1545968315600525. Epub 2015 Aug 13.

Abstract

Background Traumatic brain injury (TBI) often leads to mood and cognitive complications, affecting functional recovery. Understanding neurobiological alterations common in post-TBI depression (PTD) and cognition may identify novel biomarkers for TBI complications. Brain-derived neurotrophic factor (BDNF) is a likely target based on evidence of reduced BDNF signaling in experimental TBI and depression models and its role in learning and memory. Objective To evaluate BDNF as a biomarker for PTD, cognitive impairment, and functional cognition in a prospective cohort with severe TBI. Methods Participants with TBI (n = 113) were evaluated for PTD (Patient Health Questionnaire-9 [PHQ-9]), cognitive impairment (cognitive composite score), and functional cognition (Functional Independence Measure-Cognition, FIM-Cog). BDNF levels were measured in cerebrospinal fluid and serum at 0 to 6 days postinjury and in serum at 6 and 12 months postinjury.

Results: Serum BDNF was reduced after TBI versus controls at all time points. Acute serum BDNF positively correlated with memory composites (6 months: r = 0.43, P = .019, n = 30; 12 months: r = 0.53, P = .005, n = 26) and FIM-Memory scores (6 months: r = 0.35, P = .019, n = 45; 12 months: r = 0.38, P = .018, n = 38). Acute serum BDNF negatively correlated with 12-month PHQ-9 scores (r = -0.38; P = .044; n = 29). At 12 months, chronic serum BDNF tended to be lower in participants with PTD (P = .07) and correlated with PHQ-9 scores (r = -0.41; P = .019; n = 32). Conclusions Acute BDNF associations with memory recovery may implicate hippocampal damage/degeneration. Comparatively, BDNF associations with PTD status were not as strong as associations with PTD severity. Further investigation may delineate longitudinal BDNF patterns, and BDNF responsive treatments, reflecting mood and cognitive recovery following TBI.

Keywords: BDNF; biomarker; cognitive impairment; depression; rehabilomics; traumatic brain injury.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain Injuries, Traumatic* / blood
  • Brain Injuries, Traumatic* / cerebrospinal fluid
  • Brain Injuries, Traumatic* / complications
  • Brain-Derived Neurotrophic Factor / blood*
  • Brain-Derived Neurotrophic Factor / cerebrospinal fluid*
  • Cognition Disorders / etiology*
  • Cohort Studies
  • Depression / etiology*
  • Female
  • Humans
  • Male
  • Memory Disorders / etiology*
  • Middle Aged
  • Neuropsychological Tests
  • Statistics, Nonparametric
  • Surveys and Questionnaires
  • Trauma Severity Indices
  • Young Adult

Substances

  • Brain-Derived Neurotrophic Factor