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

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.

Are serum brain-derived neurotrophic factor concentrations related to brain structure and psychopathology in late childhood and early adolescence?

OBJECTIVE: Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence. METHODS: Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder. RESULTS: Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers. CONCLUSIONS: No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.

Effects of the brain-derived neurotropic factor variant Val66Met on cortical structure in late childhood and early adolescence.

BACKGROUND: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been associated with several neuropsychiatric disorders and regional structural brain changes in adults, but little is known about Val66Met's effect on brain morphology during typical or atypical neurodevelopment. Windows of vulnerability to psychopathology may be associated with the different alleles of the Val66Met polymorphism during childhood and adolescence. METHODOLOGY: We investigated the effect of Val66Met on cortical thickness in MRI scans of 718 children and adolescents (6-12 years old) with typical development, and in those meeting DSM criteria for a psychiatric disorder. RESULTS: Val66Met had a significant effect on cortical thickness. Considering the typically developing group, Met-carriers presented thicker parietal and occipital lobes and prefrontal cortices compared to Val homozygotes. Met-carriers with psychiatric disorders presented thicker medial and lateral temporal cortices than Val homozygotes. Furthermore, a significant genotype × psychiatric diagnosis interaction was found: Met-carriers with a psychiatric diagnosis presented thinner bilateral prefrontal cortices than Val homozygotes. CONCLUSION: This study provides evidence that Val66Met is associated with cortical maturation in children and adolescents with and without psychiatric disorders.

Neurostructural imaging findings in children with post-traumatic stress disorder: brief review.

Child maltreatment has been associated with different psychiatric disorders. Studies on both animals and humans have suggested that some brain areas would be directly affected by severe psychological trauma. The pathophysiology of post-traumatic stress disorder (PTSD) appears to be related to a complex interaction involving genetic and environmental factors. Advanced neuroimaging techniques have been used to investigate neurofunctional and neurostructural abnormalities in children, adolescents, and adults with PTSD. This review examined structural brain imaging studies that were performed in abused and traumatized children, and discusses the possible biological mechanisms involved in the pathophysiology of PTSD, the implications and future directions for magnetic resonance imaging (MRI) studies. Published reports in refereed journals were reviewed by searching Medline and examining references of the articles related to structural neuroimaging of PTSD. Structural MRI studies have been performed in adults and children to evaluate the volumetric brain alterations in the PTSD population. In contrast with studies involving adults, in which hippocampus volumetric reduction was the most consistent finding, studies involving children and adolescents with PTSD have demonstrated smaller medial and posterior portions of the corpus callosum.