Effects of the brain-derived neurotropic factor variant Val66Met on cortical structure in late childhood and early adolescence

J Psychiatr Res. 2018 Mar;98:51-58. doi: 10.1016/j.jpsychires.2017.12.008. Epub 2017 Dec 20.


Background: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been associated with several neuropsychiatric disorders and regional structural brain changes in adults, but little is known about Val66Met's effect on brain morphology during typical or atypical neurodevelopment. Windows of vulnerability to psychopathology may be associated with the different alleles of the Val66Met polymorphism during childhood and adolescence.

Methodology: We investigated the effect of Val66Met on cortical thickness in MRI scans of 718 children and adolescents (6-12 years old) with typical development, and in those meeting DSM criteria for a psychiatric disorder.

Results: Val66Met had a significant effect on cortical thickness. Considering the typically developing group, Met-carriers presented thicker parietal and occipital lobes and prefrontal cortices compared to Val homozygotes. Met-carriers with psychiatric disorders presented thicker medial and lateral temporal cortices than Val homozygotes. Furthermore, a significant genotype × psychiatric diagnosis interaction was found: Met-carriers with a psychiatric diagnosis presented thinner bilateral prefrontal cortices than Val homozygotes.

Conclusion: This study provides evidence that Val66Met is associated with cortical maturation in children and adolescents with and without psychiatric disorders.

Keywords: Adolescents; BDNF; Brain morphology; Brain-derived neurotrophic factor; Children; Cortical thickness; MRI; Psychiatric disorders; Val66Met; rs6265.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain-Derived Neurotrophic Factor / genetics*
  • Brazil
  • Cerebral Cortex / anatomy & histology*
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / growth & development*
  • Cerebral Cortex / pathology
  • Child
  • Child Development / physiology*
  • Cohort Studies
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mental Disorders / diagnostic imaging
  • Mental Disorders / genetics*
  • Mental Disorders / pathology*
  • Polymorphism, Single Nucleotide


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human