Gray matter volume in adolescent anxiety: An impact of the brain-derived neurotrophic factor Val66met polymorphism?

Sven C. Mueller, Aveline Aouidad, Elena Gorodetsky, David Goldman, Daniel S. Pine, Monique Ernst

Research output: Contribution to journalArticlepeer-review


Objective: Minimal research links anxiety disorders in adolescents to regional gray matter volume (GMV) abnormalities and their modulation by genetic factors. Prior research suggests that a brain-derived neurotrophic factor (BNDF) Val66Met polymorphism may modulate such brain morphometry profiles. Method: Using voxel-based morphometry and magnetic resonance imaging, associations of BDNF and clinical anxiety with regional GMVs of anterior cingulate cortex, insula, amygdala, and hippocampus were examined in 39 affected (17 Met allele carriers, 22 Val/Val homozygotes) and 63 nonaffected adolescents (33 Met allele carriers, 41 Val/Val homozygotes). Results: Amygdala and anterior hippocampal GMVs were significantly smaller in patients than in healthy comparison adolescents, with a reverse pattern for the insula. Post-hoc regression analyses indicated a specific contribution of social phobia to the GMV reductions in the amygdala and hippocampus. In addition, insula and dorsal-anterior cingulate cortex (ACC) GMVs were modulated by BDNF genotype. In both regions, and GMVs were larger in the Val/Val homozygote patients than in individuals carrying the Met allele. Conclusions: These results implicate reduced GMV in the amygdala and hippocampus in pediatric anxiety, particularly social phobia. In addition, the data suggest that genetic factors may modulate differences in the insula and dorsal ACC.

Original languageEnglish (US)
Pages (from-to)184-195
Number of pages12
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number2
StatePublished - Feb 2013


  • BDNF
  • adolescence
  • anxiety
  • insula
  • voxel-based morphometry

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health

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