Brain-Derived Neurotrophic Factor Val66Met and Behavioral Adjustment after Early Childhood Traumatic Brain Injury

Treble‐Barna, Amery; Wade, Shari L.; Pilipenko, Valentina; Martin, Lisa J.; Yeates, Keith Owen; Taylor, H. Gerry; Kurowski, Brad G.

doi:10.1089/neu.2020.7466

Cited by 9 publications

(5 citation statements)

References 78 publications

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“…In contrast, Met carriers have shown fewer internalizing problems (Gagner et al, 2020) and better quality of life (Tuerk et al, 2020) in a cohort of children with mild TBI. The present results are consistent with our prior report in this cohort (Treble-Barna et al, 2021), suggesting that the Met allele (associated with reduced activity-dependent secretion of BDNF) may confer risk for poorer neuroplasticity and repair mechanisms after TBI, affecting both longitudinal behavioral adjustment and neuropsychological functioning. These inconsistent findings regarding risk versus protection of the Met allele are not unique to TBI, with similar complex and conflicting findings in other clinical conditions (Hong et al, 2011;Notaras et al, 2015), perhaps most relevantly in stroke (Rezaei, Asgari Mobarake, & Saberi, 2020;Rezaei, Mobarake, Saberi, & Keshavarz, 2020).…”

Section: Discussionsupporting

confidence: 93%

“…The Met allele was similarly protective in a recent cohort of children studied at 6 months after mild TBI, with carriers having fewer internalizing problems and better quality of life (Tuerk et al, 2020). In contrast, in the present cohort, we recently observed a differential effect of Val66Met allele status in children with mostly moderate to severe TBI relative to children with orthopedic injuries (OI), such that the Met allele conferred risk for poorer longitudinal behavioral adjustment in children with TBI but not in children with OI (Treble-Barna et al, 2021). To our knowledge, no studies have yet examined the influence of BDNF Val66Met on neuropsychological outcomes after pediatric TBI.…”

Section: Introductioncontrasting

confidence: 70%

“…To our knowledge, no studies have yet examined the influence of BDNF Val66Met on neuropsychological outcomes after pediatric TBI. The present study builds on our prior work in this same cohort (Treble-Barna et al, 2021) by examining performance-based measures of neuropsychological functioning and caregiver ratings of executive function rather than parent-report measures of behavioral adjustment. Prior research in pediatric TBI and other pediatric neurological conditions has shown that neuropsychological and behavioral outcomes are associated with family environmental factors to varying degrees, with behavioral outcomes often being more sensitive to such factors compared to neuropsychological outcomes (Breslau, 1995;Taylor et al, 2008;.…”

Section: Introductionmentioning

confidence: 99%

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Brain-derived neurotrophic factor Val66Met and neuropsychological functioning after early childhood traumatic brain injury

Treble‐Barna

Wade

Pilipenko

et al. 2022

J Int Neuropsychol Soc

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Objective: The present study examined the differential effect of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on neuropsychological functioning in children with traumatic brain injury (TBI) relative to orthopedic injury (OI). Methods: Participants were drawn from a prospective, longitudinal study of children who sustained a TBI (n = 69) or OI (n = 72) between 3 and 7 years of age. Children completed a battery of neuropsychological measures targeting attention, memory, and executive functions at four timepoints spanning the immediate post-acute period to 18 months post-injury. Children also completed a comparable age-appropriate battery of measures approximately 7 years post-injury. Parents rated children’s dysexecutive behaviors at all timepoints. Results: Longitudinal mixed models revealed a significant allele status × injury group interaction with a medium effect size for verbal fluency. Cross-sectional models at 7 years post-injury revealed non-significant but medium effect sizes for the allele status x injury group interaction for fluid reasoning and immediate and delayed verbal memory. Post hoc stratified analyses revealed a consistent pattern of poorer neuropsychological functioning in Met carriers relative to Val/Val homozygotes in the TBI group, with small effect sizes; the opposite trend or no appreciable effect was observed in the OI group. Conclusions: The results suggest a differential effect of the BDNF Val66Met polymorphism on verbal fluency, and possibly fluid reasoning and immediate and delayed verbal memory, in children with early TBI relative to OI. The Met allele—associated with reduced activity-dependent secretion of BDNF—may confer risk for poorer neuropsychological functioning in children with TBI.

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Section: Discussionsupporting

confidence: 93%

Section: Introductioncontrasting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

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Brain-derived neurotrophic factor Val66Met and neuropsychological functioning after early childhood traumatic brain injury

Treble‐Barna

Wade

Pilipenko

et al. 2022

J Int Neuropsychol Soc

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“…Only a handful of studies examining BDNF genotype have been conducted in pediatric ABI, with mixed results. In a concurrent cohort study of children with moderate-to-severe TBI or orthopedic injury but no TBI (OI; comparison group), the Val66Met met allele was associated with poorer longitudinal behavioral adjustment [95] and poorer long-term neuropsychological functioning [96] in children with TBI (n = 69) but not OI (n = 72). These results suggest that the Met allele-associated with reduced activity-dependent secretion of BDNF-may confer a risk for poorer neurobehavioral recovery from pediatric TBI.…”

Section: Bdnf Genotypementioning

confidence: 99%

Brain-Derived Neurotrophic Factor in Pediatric Acquired Brain Injury and Recovery

Treble-Barna,

Petersen,

Stec

et al. 2024

Biomolecules

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We review emerging preclinical and clinical evidence regarding brain-derived neurotrophic factor (BDNF) protein, genotype, and DNA methylation (DNAm) as biomarkers of outcomes in three important etiologies of pediatric acquired brain injury (ABI), traumatic brain injury, global cerebral ischemia, and stroke. We also summarize evidence suggesting that BDNF is (1) involved in the biological embedding of the psychosocial environment, (2) responsive to rehabilitative therapies, and (3) potentially modifiable. BDNF’s unique potential as a biomarker of neuroplasticity and neural repair that is reflective of and responsive to both pre- and post-injury environmental influences separates it from traditional protein biomarkers of structural brain injury with exciting potential to advance pediatric ABI management by increasing the accuracy of prognostic tools and informing clinical decision making through the monitoring of therapeutic effects.

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“…Some single nucleotide polymorphisms (SNPs) in Apolipoprotein E (APOE), Brain Derived Neurotrophic Factor (BDNF), Glutathione S-Transferase Pi 1 (GSTP1) and Paraoxonase 1 (PON1) genes, have shown a possible role in pathways related with metal neurotoxicity (Gaynor et al 2009;Benke et al 2014;Trucco et al 2018;Della Torre et al 2018;Paes et al 2018;Cimino et al 2020;Lozano et al 2021;Treble-Barna et al 2022). For instance, a Taiwanese study (Ng et al 2015) observed that children's carriers of APOE ε4 showed a higher risk of internalizing and externalizing problems with increasing mercury at the age of two years.…”

Section: Introductionmentioning

confidence: 99%

Prenatal metals exposure and pre-adolescents’ emotional and behavioral problems

Lozano

Broberg

Soler-Blasco

et al. 2022

ISEE Conference Abstracts

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including behaviors related to anxiety, depression, somatic complaints and withdrawal) associated with changes in eating or sleeping habits, social withdrawal, violence, drug abuse, changes in personality, and teenage suicide (Liu et al. 2011). Externalizing, or behavioral, problems (including aggressive and oppositional behaviors, inattention/hyperactivity and emotion dysregulation are outward-directed symptoms (Jaspers et al. 2012) associated with poorer educational achievement, work incapacity in young adulthood and antisocial personality disorder (Narusyte et al. 2017).The prevalence of internalizing and externalizing problems in Spanish adolescents was reported to be 22.6% and 14.6%, respectively (Ortuño-Sierra et al. 2014). Pre-and postnatal environmental exposures, including outdoor, indoor, chemical and lifestyle exposures, have been related to internalizing and behavioral problems (Maitre et al. 2021;

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Brain-Derived Neurotrophic Factor Val66Met and Behavioral Adjustment after Early Childhood Traumatic Brain Injury

Cited by 9 publications

References 78 publications

Brain-derived neurotrophic factor Val66Met and neuropsychological functioning after early childhood traumatic brain injury

Brain-derived neurotrophic factor Val66Met and neuropsychological functioning after early childhood traumatic brain injury

Brain-Derived Neurotrophic Factor in Pediatric Acquired Brain Injury and Recovery

Prenatal metals exposure and pre-adolescents’ emotional and behavioral problems

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