Interactive effects of BDNF Val66Met genotype and trauma on limbic brain anatomy in childhood.
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.
Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, 71 E. Ferry Street, Detroit, MI, 48202, USA.|Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.
Hilary A
HA
Marusak
Liberty University College of Osteopathic Medicine, Lynchburg, VA, USA.
Nisha
N
Kuruvadi
Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, 71 E. Ferry Street, Detroit, MI, 48202, USA.
Angela M
AM
Vila
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
David W
DW
Shattuck
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Shantanu H
SH
Joshi
Brain and Creativity Institute, University of Southern California, Los Angeles, CA, USA.|Signal and Image Processing Institute, University of Southern California, Los Angeles, CA, USA.
Anand A
AA
Joshi
Department of Radiology, Wayne State University, Detroit, MI, USA.
Pavan K
PK
Jella
Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, 71 E. Ferry Street, Detroit, MI, 48202, USA. moriah@wayne.edu.|Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA. moriah@wayne.edu.|Perinatology Research Branch, NICHD/NIH/DHSS, Detroit, MI, USA. moriah@wayne.edu.
Moriah E
ME
Thomason
D000293:Adolescent; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D005260:Female; D005838:Genotype; D006801:Humans; D008032:Limbic System / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008715:Methionine / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014633:Valine / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D008715:Methionine; D014633:Valine
Adolescence; Brain-derived neurotrophic factor; Early adversity; Gray matter volume; Medial prefrontal cortex; Mood disorders