title: Missense Mutation of Brain Derived Neurotrophic Factor (BDNF) Alters Neurocognitive Performance in Patients with Mild Traumatic Brain Injury: A Longitudinal Study.
abstract: The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen's d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers.
authors.affiliation: Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia.
authors.forename: Vairavan
authors.initials: V
authors.lastname: Narayanan
authors.affiliation: Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia.
authors.forename: Vigneswaran
authors.identifier: http://orcid.org/0000-0003-2052-0858
authors.initials: V
authors.lastname: Veeramuthu
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Wilayah Persekutuan, Malaysia.
authors.forename: Azlina
authors.initials: A
authors.lastname: Ahmad-Annuar
authors.affiliation: University Malaya Research Imaging Centre, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia.
authors.forename: Norlisah
authors.initials: N
authors.lastname: Ramli
authors.affiliation: Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia.
authors.forename: Vicknes
authors.initials: V
authors.lastname: Waran
authors.affiliation: Julius Centre University Malaya, Department of Social and Preventive Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Karuthan
authors.initials: K
authors.lastname: Chinna
authors.affiliation: VA San Diego Healthcare System, San Diego, California, United States of America.|University of California San Diego, Department of Psychiatry, San Diego, California, United States of America.
authors.forename: Mark William
authors.initials: MW
authors.lastname: Bondi
authors.affiliation: VA San Diego Healthcare System, San Diego, California, United States of America.|University of California San Diego, Department of Psychiatry, San Diego, California, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Delano-Wood
authors.affiliation: Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia.
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Ganesan
mesh_terms: D000328:Adult; D000483:Alleles; D001924:Brain Concussion / Q000235:genetics* / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D003710:Demography; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human