Tubulin Polymerization Promoting Protein (TPPP) gene methylation and corpus callosum measures in maltreated children

Célia Maria de Araújo, James Hudziak, Deana Crocetti, Nicholas F. Wymbs, Janitza L. Montalvo-Ortiz, Catherine Orr, Matthew D. Albaugh, Robert R. Althoff, Kerry O'Loughlin, Hannah Holbrook, Hugh Garavan, Bao Zhu Yang, Stewart Mostofsky, Andrea Jackowski, Richard S. Lee, Joel Gelernter, Joan Kaufman

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number111058
JournalPsychiatry Research - Neuroimaging
StatePublished - Apr 30 2020

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Psychiatry and Mental health


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