Conflict of interest statement: No conflicts declared.
Effects of DTNBP1 genotype on brain development in children
Article first published online: 3 JUN 2011
© 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health
Journal of Child Psychology and Psychiatry
Volume 52, Issue 12, pages 1287–1294, December 2011
How to Cite
Tognin, S., Viding, E., McCrory, E. J., Taylor, L., O’Donovan, M. C., McGuire, P. and Mechelli, A. (2011), Effects of DTNBP1 genotype on brain development in children. Journal of Child Psychology and Psychiatry, 52: 1287–1294. doi: 10.1111/j.1469-7610.2011.02427.x
- Issue published online: 24 OCT 2011
- Article first published online: 3 JUN 2011
- Manuscript accepted: 3 May 2011Published online: 3 June 2011
- voxel-based morphometry
Background: Schizophrenia is a neurodevelopmental disorder, and risk genes are thought to act through disruption of brain development. Several genetic studies have identified dystrobrevin-binding protein 1 (DTNBP1, also known as dysbindin) as a potential susceptibility gene for schizophrenia, but its impact on brain development is poorly understood. The present investigation examined for the first time the effects of DTNBP1 on brain structure in children. Our hypothesis was that a genetic variation in DTNBP1 (i.e., the single nucleotide polymorphism rs2619538) would be associated with differences in both gray and white matter brain regions previously implicated in schizophrenia.
Methods: Magnetic resonance imaging and voxel-based morphometry were used to examine brain structure in 52 male children aged between 10 and 12 years. Statistical inferences on the effects of DTNBP1 genotype on gray and white matter volume (GMV and WMV) were made at p < .05 after family-wise error correction for multiple comparisons across the whole brain.
Results: Individuals homozygous for the schizophrenia high-risk allele (AA) compared with those homozygous for the low-risk allele (TT) expressed reduced GMV in the left anterior cingulate gyrus and reduced WMV in the left medial frontal area.
Conclusions: Our results suggest that genetic variation in DTNBP1 is associated with differences in gray and white matter; and that these effects are already evident in children as young as 10–12 years. These findings are consistent with the notion that the DTNBP1 genotype influences brain development and may thereby modulate vulnerability to schizophrenia.