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



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.
Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
Michelle D
MD
Failla
Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Shannon B
SB
Juengst
Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Patricia M
PM
Arenth
Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA wagnerak@upmc.edu.
Amy K
AK
Wagner
D000293:Adolescent; D000328:Adult; D000070642:Brain Injuries, Traumatic / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood* / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000209:etiology*; D015331:Cohort Studies; D003863:Depression / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D015599:Trauma Severity Indices; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor
BDNF; biomarker; cognitive impairment; depression; rehabilomics; traumatic brain injury