European Child & Adolescent Psychiatry

, Volume 25, Issue 5, pp 509–518 | Cite as

Interactive effects of BDNF Val66Met genotype and trauma on limbic brain anatomy in childhood

  • Hilary A. Marusak
  • Nisha Kuruvadi
  • Angela M. Vila
  • David W. Shattuck
  • Shantanu H. Joshi
  • Anand A. Joshi
  • Pavan K. Jella
  • Moriah E. ThomasonEmail author
Original Contribution


Childhood trauma is a major precipitating factor in psychiatric disease. Emerging data suggest that stress susceptibility is genetically determined, and that risk is mediated by changes in limbic brain circuitry. There is a need to identify markers of disease vulnerability, and it is critical that these markers be investigated in childhood and adolescence, a time when neural networks are particularly malleable and when psychiatric disorders frequently emerge. In this preliminary study, we evaluated whether a common variant in the brain-derived neurotrophic factor (BDNF) gene (Val66Met; rs6265) interacts with childhood trauma to predict limbic gray matter volume in a sample of 55 youth high in sociodemographic risk. We found trauma-by-BDNF interactions in the right subcallosal area and right hippocampus, wherein BDNF-related gray matter changes were evident in youth without histories of trauma. In youth without trauma exposure, lower hippocampal volume was related to higher symptoms of anxiety. These data provide preliminary evidence for a contribution of a common BDNF gene variant to the neural correlates of childhood trauma among high-risk urban youth. Altered limbic structure in early life may lay the foundation for longer term patterns of neural dysfunction, and hold implications for understanding the psychiatric and psychobiological consequences of traumatic stress on the developing brain.


Brain-derived neurotrophic factor Early adversity Mood disorders Gray matter volume Medial prefrontal cortex Adolescence 



Research reported in this publication was supported, in part, by the Merrill Palmer Skillman Institute and the Department of Pediatrics, Wayne State University (WSU) School of Medicine, a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (MET), NIH National Institute of Environmental Health Sciences awards P30 ES020957 and R21 ES026022 (MET), and the NIH National Institute of Neurological Disorders And Stroke award R01 NS074980 (DWS and AAJ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The WSU Genomics Core is supported, in part, by NIH National Cancer Institute award P30 CA022453. The authors thank Zahid Latif and Yashwanth Katkuri of WSU for their assistance in neuroimaging data acquisition, Kayla Martin, Gregory H. Baldwin, Rita Elias, Melissa Youmans, Mallory Gardner, Amy Katherine Swartz, Timothy Lozon, Berta Rihan, and Ali Daher of WSU for assistance in participant recruitment and data collection, Julianne Facca, Matthew Hess, and Susan Land of the WSU Applied Genomics Technology Center for assistance with genetic analyses, and the children and families who generously shared their time.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Hilary A. Marusak
    • 1
    • 2
  • Nisha Kuruvadi
    • 3
  • Angela M. Vila
    • 1
  • David W. Shattuck
    • 4
  • Shantanu H. Joshi
    • 4
  • Anand A. Joshi
    • 5
    • 6
  • Pavan K. Jella
    • 7
  • Moriah E. Thomason
    • 1
    • 8
    • 9
    Email author
  1. 1.Merrill Palmer Skillman Institute for Child and Family DevelopmentWayne State UniversityDetroitUSA
  2. 2.Department of Psychiatry and Behavioral NeurosciencesWayne State University School of MedicineDetroitUSA
  3. 3.Liberty University College of Osteopathic MedicineLynchburgUSA
  4. 4.Department of Neurology, David Geffen School of MedicineUniversity of California, Los AngelesLos AngelesUSA
  5. 5.Brain and Creativity InstituteUniversity of Southern CaliforniaLos AngelesUSA
  6. 6.Signal and Image Processing InstituteUniversity of Southern CaliforniaLos AngelesUSA
  7. 7.Department of RadiologyWayne State UniversityDetroitUSA
  8. 8.Department of PediatricsWayne State University School of MedicineDetroitUSA
  9. 9.Perinatology Research BranchNICHD/NIH/DHSSDetroitUSA

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