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Updated: Dec 27, 2025
Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
Published on: July 12, 2012
Tubulin Polymerization Promoting Protein (TPPP) gene methylation and corpus callosum measures in maltreated children
Célia Maria de Araújo1, James Hudziak2, Deana Crocetti3
1Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, United States; Universidade Federal de São Paulo, São Paulo, Brazil.
Insights
Tubulin Polymerization Promoting Protein (TPPP) methylation interacts with childhood trauma to affect corpus callosum (CC) structure and white matter integrity. These findings suggest TPPP
Area of Science:
- Neuroscience
- Epigenetics
- Child Psychology
Background:
- Tubulin Polymerization Promoting Protein (TPPP) plays a role in brain white matter development.
- Previous studies linked TPPP to stress-related psychiatric disorders.
- Childhood maltreatment is a risk factor for psychiatric disorders and can impact brain development.
Purpose of the Study:
- To investigate the impact of TPPP methylation on corpus callosum (CC) structural and fractional anisotropy (FA) measures.
- To explore the interaction between TPPP methylation and childhood trauma experiences on CC development.
- To understand the epigenetic mechanisms underlying brain changes in children exposed to stress.
Main Methods:
- Utilized voxel-based morphometry (VBM) for structural brain data analysis.
- Determined fractional anisotropy (FA) using an atlas-based approach.
- Analyzed DNA methylation data from saliva using Illumina 450K and 850K arrays in 63 children.
Main Results:
- TPPP methylation, interacting with trauma severity, predicted CC body volume and FA in the genu, body, and splenium.
- These associations were significant after controlling for covariates.
- Findings in the splenium were replicated using both 450K and 850K methylation data.
Conclusions:
- TPPP methylation is associated with structural and microstructural changes in the corpus callosum in children exposed to trauma.
- This suggests a potential epigenetic mechanism linking TPPP, stress, and brain alterations relevant to psychiatric disorders.
- The study highlights the role of TPPP in neurodevelopmental trajectories under stress.
Abstract:
The goal of the current study was to evaluate the impact of Tubulin Polymerization Promoting Protein (TPPP) methylation on structural and fractional anisotropy (FA) corpus callosum (CC) measures. TPPP is involved in the development of white matter tracts in the brain and was implicated in stress-related psychiatric disorders in an unbiased whole epigenome methylation study. The cohort included 63 participants (11.73 y/o ±1.91) from a larger study investigating risk and resilience in maltreated children. Voxel-based morphometry (VBM) was used to process the structural data, fractional anisotropy (FA) was determined using an atlas-based approach, and DNA specimens were derived from saliva in two batches using the 450 K (N = 39) and 850 K (N = 24) Illumina arrays, with the data from each batch analyzed separately. After controlling for multiple comparisons and relevant covariates (e.g., demographics, brain volume, cell composition, 3 PCs), 850 K derived TPPP methylation values, in interaction with a dimensional measure of children's trauma experiences, predicted left and right CC body volumes and genu, body and splenium FA (p < .007, all comparisons). The findings in the splenium replicated in subjects with the 450 K data. The results extend prior investigations and suggest a role for TPPP in brain changes associated with stress-related psychiatric disorders.
